A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer (JACOB)

• ClinicalTrials.gov Identifier: NCT01774786
• Recruitment Status: Completed
• First Posted: January 24, 2013
• Results First Posted: February 14, 2018
• Last Update Posted: December 30, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Gastric Cancer
• Interventions: Drug: 5-Fluorouracil; Drug: Capecitabine; Drug: Cisplatin; Drug: Pertuzumab; Drug: Placebo; Drug: Trastuzumab
• Enrollment: 780

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 780 participants were enrolled in the study.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Period Title: Overall Study
Started [1]	388	392
Did Not Receive Any Study Treatment	4 [2]	3 [3]
Received at Least One Dose of Pertuzumab [4]	384	1 [5]
Received Placebo (No Pertuzumab) [6]	0	388
Completed	60	46
Not Completed	328	346
Reason Not Completed
Death	300	319
Lost to Follow-up	6	7
Withdrawal by Subject	18	14
Physician Decision	2	0
Non-compliance	0	1
Reason Not Specified	2	5
[1] Intent-to-Treat (ITT) population; [2] 2 patients found ineligible after enrollment and 2 patients died before treatment.; [3] All 3 patients found ineligible for the study after enrollment and before treatment.; [4] Pertuzumab Safety Population; [5] One participant randomized to placebo arm received 1 dose of pertuzumab by error.; [6] Placebo Safety Population

Baseline Characteristics

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy	Total
Arm/Group Description		Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Total of all reporting groups
Overall Number of Baseline Participants		388	392	780
Baseline Analysis Population Description		The Intent-to-Treat (ITT) population included all randomized participants regardless of whether treatment was actually received, with participants grouped according to the treatment assigned at randomization.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	388 participants	392 participants	780 participants
		60.9 (11.3)	60.1 (10.7)	60.5 (11.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	388 participants	392 participants	780 participants
	Female	94 24.2%	69 17.6%	163 20.9%
	Male	294 75.8%	323 82.4%	617 79.1%
Geographic Region [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	388 participants	392 participants	780 participants
	Asia (excluding Japan)	143 36.9%	146 37.2%	289 37.1%
	Japan	40 10.3%	40 10.2%	80 10.3%
	North America/Western Europe/Australia	133 34.3%	133 33.9%	266 34.1%
	South America/Eastern Europe	72 18.6%	73 18.6%	145 18.6%
		[1] Measure Description: Participants were stratified at randomization according to geographic region, prior gastrectomy, and HER2 status.
Prior Gastrectomy [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	388 participants	392 participants	780 participants
	Prior Gastrectomy	105 27.1%	102 26.0%	207 26.5%
	No Prior Gastrectomy	283 72.9%	290 74.0%	573 73.5%
		[1] Measure Description: Participants were stratified at randomization according to geographic region, prior gastrectomy, and HER2 status.
Human Epidermal Growth Factor Receptor 2 (HER2) Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	388 participants	392 participants	780 participants
	IHC 2+/ISH+	129 33.2%	130 33.2%	259 33.2%
	IHC 3+	259 66.8%	262 66.8%	521 66.8%
		[1] Measure Description: Participants were stratified at randomization according to geographic region, prior gastrectomy, and HER2 status. HER2 positivity of tumor specimens from each participant were determined by central laboratory testing. The IHC gives a score of 0 to 3+ that measures the amount of HER2 proteins on the surface of cells. A participant's cancer was considered HER2-positive with an IHC score of 2+ that was confirmed by ISH positivity or by an IHC score of 3+. IHC = immunohistochemistry; ISH = in-situ hybridization
Measurability of Disease, per RECIST v1.1; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	388 participants	392 participants	780 participants
	Measurable Disease	351 90.5%	352 89.8%	703 90.1%
	Non-Measurable Evaluable Disease Only	37 9.5%	40 10.2%	77 9.9%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as the time from randomization to death from any cause. For participants who were still alive on the date of clinical data cut-off for the OS analysis, the last date when the participant was known to be alive on, or prior to the clinical cut-off date, was used to determine the censoring date. Participants who did not have any post-baseline data (e.g., dosing records, imaging dates, visit dates) were censored at the date of randomization plus 1 day.
Time Frame	From Baseline until death from any cause (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.4 [0-42] months vs. 25.0 [0-41] months; Final Analysis: 46.1 [0-70] months vs. 44.4 [0-68] months)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all randomized participants, regardless of whether study medication was received.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed	388	392
Median (95% Confidence Interval); Unit of Measure: Months
Primary Analysis	17.5; (16.2 to 19.3)	14.2; (12.9 to 15.5)
Final Analysis	18.1; (16.2 to 19.5)	14.2; (12.9 to 15.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Primary Analysis. The null hypothesis is that the survival distribution of OS is the same in the two treatment arms.
	Type of Statistical Test	Superiority
	Comments	The study was designed to have 80% power to show a significant difference with respect to the primary endpoint.
Statistical Test of Hypothesis	P-Value	0.0565
	Comments	The actual p-value significance threshold required for OS was 0.0455, after alpha spent at the interim analysis was taken into account.
	Method	Stratified Log-Rank
	Comments	Stratified analysis by geographic region, HER2 status, and prior gastrectomy.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.00
	Estimation Comments	HR was calculated as pertuzumab arm vs. placebo arm.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Final Analysis
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.72 to 0.99
	Estimation Comments	HR was calculated as pertuzumab arm vs. placebo arm. Stratified analysis by geographic region, HER2 status, and prior gastrectomy.

2. Secondary Outcome

Title	Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Description	Progression-free survival (PFS) is defined as the time from randomization to the first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Tumor assessments with CT or MRI scans of the chest, abdomen, and pelvis were performed every 9 weeks. Participants without documented PD or death were censored at the tumor assessment date for which the participant was last known to be progression-free. Participants who did not have any post-baseline tumor assessment data were censored at the date of randomization plus 1 day. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 millimeters (mm) in the sum of diameters of target lesions; the appearance of one or more new lesions.
Time Frame	Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants, regardless of whether study medication was received.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed	388	392
Median (95% Confidence Interval); Unit of Measure: months
Primary Analysis	8.5; (8.2 to 9.7)	7.0; (6.4 to 8.2)
Final Analysis	8.5; (8.3 to 9.7)	7.2; (6.4 to 8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Primary Analysis
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.86
	Estimation Comments	A stratified Cox proportional hazards regression model was used to estimate the HR between the pertuzumab arm vs. the placebo arm.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Final Analysis
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.85
	Estimation Comments	A stratified Cox proportional hazards regression model was used to estimate the HR between the pertuzumab arm vs. the placebo arm.

3. Secondary Outcome

Title	Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
Description	The overall objective response rate was defined as the percentage of participants with partial response (PR) or complete response (CR) occurring on two consecutive occasions ≥4 weeks apart, as determined by the investigator using RECIST v1.1. Tumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis were performed every 9 weeks. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be greater than or equal to (≥) 15 mm in short axis when assessed by CT scan.
Time Frame	Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)

Outcome Measure Data

Analysis Population Description

The subset of participants with measurable disease at baseline, according to RECIST v1.1 criteria.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed	351	352
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Objective Response (CR + PR)	56.7; (51.33 to 61.95)	48.3; (42.97 to 53.65)
Complete Response (CR)	5.1; (3.07 to 7.98)	0.9; (0.18 to 2.47)
Partial Response (PR)	51.6; (46.20 to 56.91)	47.4; (42.13 to 52.80)
Stable Disease (SD)	27.9; (23.29 to 32.93)	33.0; (28.06 to 38.14)
Progressive Disease (PD)	4.8; (2.85 to 7.64)	8.0; (5.35 to 11.29)
Not Evaluable/Missing	10.5; (7.53 to 14.24)	10.8; (7.75 to 14.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Primary Analysis of Objective Response Rate
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Difference in Objective Response
	Estimated Value	8.40
	Confidence Interval	(2-Sided) 95%; 0.89 to 15.91
	Estimation Comments	Difference in objective response was calculated as the pertuzumab arm minus placebo arm.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Primary Analysis of Objective Response Rate
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 1.04 to 1.89
	Estimation Comments	Odds ratio was calculated as the pertuzumab arm vs. placebo arm.

4. Secondary Outcome

Title	Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
Description	The overall objective response rate was defined as the percentage of participants with partial response (PR) or complete response (CR) occurring on two consecutive occasions ≥4 weeks apart, as determined by the investigator using RECIST v1.1. Tumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis were performed every 9 weeks. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be greater than or equal to (≥) 15 mm in short axis when assessed by CT scan.
Time Frame	Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Final Analysis: 50.4 [0-70] months vs. 47.4 [0-66] months)

Outcome Measure Data

Analysis Population Description

The subset of participants with measurable disease at baseline, according to RECIST v1.1 criteria.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed	351	352
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Objective Response (CR + PR)	57.0; (51.62 to 62.22)	48.6; (43.25 to 53.94)
Complete Response (CR)	5.7; (3.51 to 8.66)	2.0; (0.80 to 4.05)
Partial Response (PR)	51.3; (45.92 to 56.62)	46.6; (41.29 to 51.95)
Stable Disease (SD)	27.6; (23.02 to 32.63)	32.7; (27.79 to 37.84)
Progressive Disease (PD)	4.8; (2.85 to 7.64)	8.2; (5.59 to 11.62)
Not Evaluable/Missing	10.5; (7.53 to 14.24)	10.5; (7.51 to 14.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Final Analysis of Objective Response Rate
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Difference in Objective Response
	Estimated Value	8.40
	Confidence Interval	(2-Sided) 95%; 0.89 to 15.91
	Estimation Comments	Difference in objective response was calculated as the pertuzumab arm minus placebo arm.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Final Analysis of Objective Response Rate
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 1.04 to 1.89
	Estimation Comments	Odds ratio was calculated as the pertuzumab arm vs. placebo arm.

5. Secondary Outcome

Title	Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria
Description	Duration of objective response is defined as the time from first occurrence of documented objective response to documented disease progression, as determined by the investigator using RECIST v1.1, or death from any cause. Objective response: PR or CR occurring on 2 consecutive occasions ≥4 weeks apart. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions. Measurable disease defined as tumor lesions with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node, it must be ≥15 mm in short axis when assessed by CT scan.
Time Frame	Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)

Outcome Measure Data

Analysis Population Description

The participants with measurable disease at baseline who achieved a documented objective response, according to RECIST v1.1 criteria.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed		200	171
Median (95% Confidence Interval); Unit of Measure: months
Primary Analysis	Number Analyzed	199 participants	170 participants
		10.2; (8.4 to 10.7)	8.4; (6.8 to 8.7)
Final Analysis	Number Analyzed	200 participants	171 participants
		10.2; (8.5 to 11.6)	8.4; (6.7 to 9.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Primary Analysis
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.06
	Estimation Comments	HR was calculated as pertuzumab arm vs. placebo arm. Stratified analysis by geographic region, HER2 status, and prior gastrectomy.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Final Analysis
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.98
	Estimation Comments	HR was calculated as pertuzumab arm vs. placebo arm. Stratified analysis by geographic region, HER2 status, and prior gastrectomy.

6. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria
Description	The clinical benefit rate was defined as best response of complete response (CR) or partial response (PR) or stable disease (SD) for 6 weeks or longer, as determined by the investigator using RECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum diameters while on study. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be >/=15 mm in short axis when assessed by CT scan. The clinical benefit rate was not updated at the final analysis.
Time Frame	Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)

Outcome Measure Data

Analysis Population Description

The subset of participants with measurable disease at baseline, according to RECIST v1.1 criteria.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed	351	352
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	84.6; (80.41 to 88.23)	81.3; (76.77 to 85.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Difference in Clinical Benefit Rate
	Estimated Value	3.37
	Confidence Interval	(2-Sided) 95%; -2.34 to 9.07
	Estimation Comments	Difference in clinical benefit rate was calculated as the pertuzumab arm minus placebo arm.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Exploratory
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.88
	Estimation Comments	Odds ratio was calculated as the pertuzumab arm vs. placebo arm.

7. Secondary Outcome

Title	Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03
Description	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. The investigator graded all AEs for severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.
Time Frame	From Baseline until end of post-treatment follow-up (up to 70 months)

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received any amount of any study medication. Those who received any amount of pertuzumab were included in the pertuzumab arm; all other treated participants were included in the placebo arm.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed	385	388
Measure Type: Count of Participants; Unit of Measure: Participants
Any Adverse Event (AE)	381 99.0%	385 99.2%
AE with Fatal Outcome	27 7.0%	31 8.0%
Serious AE	178 46.2%	156 40.2%
Grade 3-5 AE	310 80.5%	288 74.2%
AE Leading to Pertuz/Pbo & Trastuz Discontinuation	48 12.5%	46 11.9%
AE Leading to Dose Interruption &/or Dose Delay	110 28.6%	94 24.2%

8. Secondary Outcome

Title	Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD)
Description	The number and percentage of participants with symptomatic left ventricular systolic dysfunction (LVSD) and asymptomatic LVSD events (defined as a left ventricular ejection fraction [LVEF] ≥10% decrease from baseline to an absolute value <50%) at any time during the study was summarized by treatment arm.
Time Frame	From Baseline until end of post-treatment follow-up (up to 70 months)

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received any amount of any study medication. Those who received any amount of pertuzumab were included in the pertuzumab arm; all other treated participants were included in the placebo arm.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed	385	388
Measure Type: Count of Participants; Unit of Measure: Participants
Symptomatic LVSD	3 0.8%	1 0.3%
Asymptomatic LVSD	20 5.2%	18 4.6%

9. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
Description	The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).
Time Frame	Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)

Outcome Measure Data

Analysis Population Description

Participants in the ITT population (includes all randomized participants, regardless of whether study medication was received) with both a baseline assessment and at least 1 post-treatment assessment are included in the analysis.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed		388	392
Mean (Standard Deviation); Unit of Measure: score on a scale
Appetite Loss: Cycle 1 (Baseline)	Number Analyzed	371 participants	383 participants
		26.68 (28.65)	27.59 (29.96)
Appetite Loss: Change at Cycle 2	Number Analyzed	335 participants	343 participants
		6.57 (33.18)	0.97 (35.86)
Appetite Loss: Change at Cycle 3	Number Analyzed	321 participants	315 participants
		3.63 (36.19)	3.81 (36.76)
Appetite Loss: Change at Cycle 4	Number Analyzed	299 participants	294 participants
		5.24 (34.20)	0.79 (34.33)
Appetite Loss: Change at Cycle 5	Number Analyzed	286 participants	287 participants
		4.55 (36.50)	2.90 (35.85)
Appetite Loss: Change at Cycle 6	Number Analyzed	271 participants	257 participants
		3.94 (36.07)	-0.39 (36.86)
Appetite Loss: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		2.07 (38.05)	1.61 (35.98)
Appetite Loss: Change at Cycle 8	Number Analyzed	234 participants	217 participants
		-2.42 (33.81)	-3.69 (34.20)
Appetite Loss: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		-6.67 (31.92)	-4.76 (31.67)
Appetite Loss: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-8.06 (32.52)	-6.63 (28.48)
Appetite Loss: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		-9.36 (33.19)	-9.68 (27.38)
Appetite Loss: Change at Cycle 12	Number Analyzed	159 participants	140 participants
		-9.22 (33.73)	-9.05 (28.51)
Appetite Loss: Change at Cycle 13	Number Analyzed	141 participants	111 participants
		-10.17 (31.10)	-10.81 (29.18)
Appetite Loss: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-12.10 (31.96)	-12.09 (30.32)
Appetite Loss: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		-8.21 (32.96)	-9.18 (29.81)
Appetite Loss: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-6.03 (33.07)	-10.59 (28.74)
Appetite Loss: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-6.55 (29.29)	-9.91 (29.05)
Appetite Loss: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-4.90 (31.25)	-14.08 (27.98)
Appetite Loss: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		-8.33 (31.34)	-13.13 (28.57)
Appetite Loss: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-3.97 (31.65)	-13.23 (29.66)
Appetite Loss: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		-5.91 (31.01)	-14.20 (32.76)
Appetite Loss: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-4.98 (34.45)	-16.31 (29.38)
Appetite Loss: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-6.35 (36.84)	-11.36 (35.90)
Appetite Loss: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-7.78 (33.82)	-13.33 (30.00)
Appetite Loss: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-7.05 (35.14)	-12.04 (31.02)
Appetite Loss: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-7.48 (34.87)	-12.50 (32.52)
Appetite Loss: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-10.08 (33.76)	-9.20 (28.03)
Appetite Loss: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-10.00 (32.20)	-11.54 (29.73)
Appetite Loss: Change at PT Visit 1	Number Analyzed	178 participants	202 participants
		7.30 (36.86)	2.64 (33.14)
Appetite Loss: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-0.33 (33.83)	4.55 (34.53)
Cognitive Functional Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	382 participants
		87.95 (17.32)	88.22 (16.18)
Cognitive Functional Scale: Change at Cycle 2	Number Analyzed	333 participants	341 participants
		-1.90 (17.82)	-1.81 (16.93)
Cognitive Functional Scale: Change at Cycle 3	Number Analyzed	321 participants	315 participants
		-0.83 (17.11)	-3.17 (18.30)
Cognitive Functional Scale: Change at Cycle 4	Number Analyzed	302 participants	295 participants
		-2.04 (17.78)	-2.99 (19.28)
Cognitive Functional Scale: Change at Cycle 5	Number Analyzed	285 participants	287 participants
		-3.04 (19.09)	-4.59 (19.59)
Cognitive Functional Scale: Change at Cycle 6	Number Analyzed	271 participants	256 participants
		-5.10 (19.23)	-3.84 (19.00)
Cognitive Functional Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		-4.34 (19.52)	-4.31 (19.09)
Cognitive Functional Scale: Change at Cycle 8	Number Analyzed	233 participants	217 participants
		-3.15 (17.90)	-3.30 (17.59)
Cognitive Functional Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		-2.22 (18.53)	-4.59 (18.53)
Cognitive Functional Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-3.32 (19.44)	-3.11 (18.50)
Cognitive Functional Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		-2.83 (18.44)	-3.44 (17.06)
Cognitive Functional Scale: Change at Cycle 12	Number Analyzed	159 participants	139 participants
		-3.35 (20.00)	-2.52 (18.16)
Cognitive Functional Scale: Change at Cycle 13	Number Analyzed	140 participants	111 participants
		-1.79 (19.04)	-3.60 (17.89)
Cognitive Functional Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-1.98 (19.00)	-2.29 (17.56)
Cognitive Functional Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		-1.15 (18.47)	-2.38 (16.05)
Cognitive Functional Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-2.73 (17.16)	-2.55 (17.16)
Cognitive Functional Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-2.53 (17.21)	-1.13 (15.44)
Cognitive Functional Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-2.78 (18.18)	0.47 (16.42)
Cognitive Functional Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		-1.04 (18.07)	0.00 (14.62)
Cognitive Functional Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-2.18 (19.67)	0.79 (15.68)
Cognitive Functional Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		-2.11 (20.56)	0.62 (16.50)
Cognitive Functional Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-4.73 (18.98)	-0.71 (18.04)
Cognitive Functional Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-2.38 (19.60)	1.14 (17.75)
Cognitive Functional Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-2.78 (19.69)	1.25 (16.18)
Cognitive Functional Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-5.45 (16.41)	-0.93 (18.66)
Cognitive Functional Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-2.38 (16.32)	-1.56 (18.63)
Cognitive Functional Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-3.88 (18.84)	-1.15 (18.33)
Cognitive Functional Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-3.75 (15.78)	0.00 (20.00)
Cognitive Functional Scale: Change at PT Visit 1	Number Analyzed	177 participants	202 participants
		-9.13 (21.90)	-9.16 (20.02)
Cognitive Functional Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-8.42 (20.22)	-11.21 (22.48)
Constipation Symptom Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	382 participants
		20.43 (28.45)	18.41 (27.13)
Constipation Symptom Scale: Change at Cycle 2	Number Analyzed	334 participants	341 participants
		-5.39 (27.05)	0.29 (27.23)
Constipation Symptom Scale: Change at Cycle 3	Number Analyzed	321 participants	316 participants
		-7.48 (28.98)	-2.11 (27.65)
Constipation Symptom Scale: Change at Cycle 4	Number Analyzed	301 participants	295 participants
		-5.32 (29.21)	-3.73 (28.26)
Constipation Symptom Scale: Change at Cycle 5	Number Analyzed	286 participants	287 participants
		-5.94 (29.15)	-1.28 (27.64)
Constipation Symptom Scale: Change at Cycle 6	Number Analyzed	271 participants	257 participants
		-7.13 (29.65)	-2.33 (30.24)
Constipation Symptom Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		-8.13 (30.11)	-4.09 (29.06)
Constipation Symptom Scale: Change at Cycle 8	Number Analyzed	232 participants	217 participants
		-8.05 (30.90)	-4.45 (27.32)
Constipation Symptom Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		-10.00 (27.10)	-5.61 (26.74)
Constipation Symptom Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-9.32 (29.56)	-7.43 (26.81)
Constipation Symptom Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		-9.16 (29.60)	-6.88 (27.84)
Constipation Symptom Scale: Change at Cycle 12	Number Analyzed	159 participants	138 participants
		-10.27 (29.04)	-7.25 (25.39)
Constipation Symptom Scale: Change at Cycle 13	Number Analyzed	140 participants	110 participants
		-11.19 (29.55)	-5.76 (26.27)
Constipation Symptom Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-11.60 (27.11)	-6.21 (26.00)
Constipation Symptom Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		-10.51 (26.59)	-7.14 (24.52)
Constipation Symptom Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-8.62 (24.91)	-7.45 (25.39)
Constipation Symptom Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-8.33 (24.30)	-5.86 (18.59)
Constipation Symptom Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-7.52 (22.93)	-6.57 (26.20)
Constipation Symptom Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		-3.47 (25.81)	-3.03 (25.97)
Constipation Symptom Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-3.97 (26.08)	-4.76 (26.68)
Constipation Symptom Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		-3.80 (29.23)	-9.26 (25.42)
Constipation Symptom Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-4.98 (28.58)	-8.51 (27.34)
Constipation Symptom Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-6.35 (28.62)	-8.33 (26.04)
Constipation Symptom Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-7.78 (27.01)	-10.00 (26.37)
Constipation Symptom Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-7.05 (29.77)	-9.26 (28.30)
Constipation Symptom Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-6.12 (30.94)	-6.25 (23.09)
Constipation Symptom Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-7.75 (28.95)	-10.34 (26.88)
Constipation Symptom Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-6.67 (26.37)	-6.41 (21.12)
Constipation Symptom Scale: Change at PT Visit 1	Number Analyzed	177 participants	202 participants
		-6.78 (31.45)	-4.62 (26.19)
Constipation Symptom Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-6.93 (28.41)	-0.91 (31.11)
Diarrhea Symptom Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	382 participants
		8.87 (17.70)	9.16 (18.87)
Diarrhea Symptom Scale: Change at Cycle 2	Number Analyzed	333 participants	340 participants
		15.12 (30.42)	5.20 (23.79)
Diarrhea Symptom Scale: Change at Cycle 3	Number Analyzed	321 participants	314 participants
		14.64 (27.71)	4.99 (26.10)
Diarrhea Symptom Scale: Change at Cycle 4	Number Analyzed	302 participants	295 participants
		14.13 (27.15)	4.63 (24.07)
Diarrhea Symptom Scale: Change at Cycle 5	Number Analyzed	286 participants	287 participants
		13.17 (25.47)	4.99 (23.70)
Diarrhea Symptom Scale: Change at Cycle 6	Number Analyzed	270 participants	256 participants
		14.81 (27.01)	2.47 (23.76)
Diarrhea Symptom Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		12.26 (23.74)	2.92 (23.44)
Diarrhea Symptom Scale: Change at Cycle 8	Number Analyzed	232 participants	217 participants
		8.91 (23.56)	2.61 (23.53)
Diarrhea Symptom Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		6.83 (23.76)	2.04 (21.25)
Diarrhea Symptom Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		6.63 (23.97)	0.60 (20.91)
Diarrhea Symptom Scale: Change at Cycle 11	Number Analyzed	171 participants	154 participants
		5.26 (21.80)	2.60 (20.36)
Diarrhea Symptom Scale: Change at Cycle 12	Number Analyzed	159 participants	139 participants
		3.98 (22.30)	1.92 (19.97)
Diarrhea Symptom Scale: Change at Cycle 13	Number Analyzed	140 participants	111 participants
		4.29 (24.27)	1.50 (19.27)
Diarrhea Symptom Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		3.95 (24.45)	0.98 (20.15)
Diarrhea Symptom Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		3.33 (23.79)	1.02 (19.42)
Diarrhea Symptom Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		5.46 (21.06)	3.14 (15.10)
Diarrhea Symptom Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		2.68 (21.05)	2.25 (14.94)
Diarrhea Symptom Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		3.59 (21.95)	3.29 (17.95)
Diarrhea Symptom Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		3.82 (19.86)	2.02 (16.41)
Diarrhea Symptom Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		5.95 (19.47)	3.70 (17.05)
Diarrhea Symptom Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		3.80 (23.26)	1.85 (16.40)
Diarrhea Symptom Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		6.97 (24.98)	4.26 (17.88)
Diarrhea Symptom Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		6.88 (21.72)	8.33 (20.49)
Diarrhea Symptom Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		7.22 (22.21)	3.33 (16.54)
Diarrhea Symptom Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		8.97 (23.91)	2.78 (14.64)
Diarrhea Symptom Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		5.44 (21.89)	5.21 (20.93)
Diarrhea Symptom Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		3.88 (22.07)	3.45 (16.29)
Diarrhea Symptom Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		7.50 (27.72)	2.56 (16.12)
Diarrhea Symptom Scale: Change at PT Visit 1	Number Analyzed	176 participants	202 participants
		8.14 (26.00)	1.98 (24.35)
Diarrhea Symptom Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		7.26 (25.65)	4.24 (29.65)
Dyspnoea Symptom Scale: Cycle 1 (Baseline)	Number Analyzed	370 participants	382 participants
		12.07 (17.99)	12.65 (20.20)
Dyspnoea Symptom Scale: Change at Cycle 2	Number Analyzed	335 participants	341 participants
		-0.50 (19.04)	0.29 (19.72)
Dyspnoea Symptom Scale: Change at Cycle 3	Number Analyzed	320 participants	314 participants
		-0.31 (20.18)	-0.32 (20.38)
Dyspnoea Symptom Scale: Change at Cycle 4	Number Analyzed	299 participants	294 participants
		1.23 (20.31)	1.81 (21.08)
Dyspnoea Symptom Scale: Change at Cycle 5	Number Analyzed	284 participants	287 participants
		2.58 (20.62)	1.39 (21.18)
Dyspnoea Symptom Scale: Change at Cycle 6	Number Analyzed	271 participants	256 participants
		3.20 (23.79)	0.39 (20.55)
Dyspnoea Symptom Scale: Change at Cycle 7	Number Analyzed	241 participants	227 participants
		0.00 (21.94)	0.59 (20.07)
Dyspnoea Symptom Scale: Change at Cycle 8	Number Analyzed	233 participants	216 participants
		-0.14 (21.99)	0.93 (20.56)
Dyspnoea Symptom Scale: Change at Cycle 9	Number Analyzed	209 participants	196 participants
		-1.12 (20.51)	0.17 (18.95)
Dyspnoea Symptom Scale: Change at Cycle 10	Number Analyzed	185 participants	166 participants
		-0.54 (21.56)	1.00 (16.99)
Dyspnoea Symptom Scale: Change at Cycle 11	Number Analyzed	170 participants	155 participants
		-2.16 (19.58)	-1.29 (17.77)
Dyspnoea Symptom Scale: Change at Cycle 12	Number Analyzed	158 participants	140 participants
		-2.53 (19.75)	-0.71 (18.95)
Dyspnoea Symptom Scale: Change at Cycle 13	Number Analyzed	140 participants	111 participants
		-1.43 (20.34)	-1.20 (16.77)
Dyspnoea Symptom Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-1.98 (19.00)	-2.61 (17.98)
Dyspnoea Symptom Scale: Change at Cycle 15	Number Analyzed	129 participants	98 participants
		-2.84 (21.26)	2.72 (18.95)
Dyspnoea Symptom Scale: Change at Cycle 16	Number Analyzed	115 participants	85 participants
		-1.45 (20.42)	1.18 (18.86)
Dyspnoea Symptom Scale: Change at Cycle 17	Number Analyzed	110 participants	74 participants
		-1.82 (20.61)	0.90 (19.87)
Dyspnoea Symptom Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-0.98 (20.15)	-2.35 (18.10)
Dyspnoea Symptom Scale: Change at Cycle 19	Number Analyzed	96 participants	65 participants
		-1.74 (20.73)	0.51 (18.15)
Dyspnoea Symptom Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-1.19 (20.98)	-1.06 (16.90)
Dyspnoea Symptom Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		1.27 (22.29)	-0.62 (19.95)
Dyspnoea Symptom Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-1.99 (22.38)	0.71 (14.73)
Dyspnoea Symptom Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-1.59 (21.94)	1.52 (14.30)
Dyspnoea Symptom Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		1.11 (22.10)	-1.67 (12.96)
Dyspnoea Symptom Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		0.64 (21.38)	-3.70 (15.49)
Dyspnoea Symptom Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		0.00 (22.57)	1.04 (23.16)
Dyspnoea Symptom Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		0.78 (21.19)	3.45 (22.44)
Dyspnoea Symptom Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		1.67 (21.28)	3.85 (17.20)
Dyspnoea Symptom Scale: Change at PT Visit 1	Number Analyzed	177 participants	202 participants
		6.97 (26.98)	6.77 (23.82)
Dyspnoea Symptom Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		3.30 (23.81)	9.39 (26.76)
Emotional Functional Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	382 participants
		76.90 (20.21)	76.56 (19.84)
Emotional Functional Scale: Change at Cycle 2	Number Analyzed	333 participants	341 participants
		3.53 (16.84)	3.05 (18.49)
Emotional Functional Scale: Change at Cycle 3	Number Analyzed	321 participants	315 participants
		2.65 (18.63)	3.96 (19.95)
Emotional Functional Scale: Change at Cycle 4	Number Analyzed	302 participants	295 participants
		3.10 (21.11)	3.67 (20.44)
Emotional Functional Scale: Change at Cycle 5	Number Analyzed	286 participants	287 participants
		2.62 (19.97)	2.74 (21.72)
Emotional Functional Scale: Change at Cycle 6	Number Analyzed	271 participants	256 participants
		1.01 (19.64)	4.93 (21.00)
Emotional Functional Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		1.72 (21.09)	4.41 (20.18)
Emotional Functional Scale: Change at Cycle 8	Number Analyzed	233 participants	217 participants
		3.43 (20.66)	5.66 (19.63)
Emotional Functional Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		4.72 (20.10)	4.78 (19.45)
Emotional Functional Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		3.72 (21.76)	6.74 (18.13)
Emotional Functional Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		5.85 (19.64)	4.96 (19.21)
Emotional Functional Scale: Change at Cycle 12	Number Analyzed	159 participants	139 participants
		4.93 (21.38)	5.24 (19.14)
Emotional Functional Scale: Change at Cycle 13	Number Analyzed	140 participants	111 participants
		5.00 (23.07)	5.18 (17.95)
Emotional Functional Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		5.93 (22.90)	6.29 (19.03)
Emotional Functional Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		6.03 (22.13)	5.19 (19.61)
Emotional Functional Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		5.17 (23.20)	5.29 (20.81)
Emotional Functional Scale: Change at Cycle 17	Number Analyzed	111 participants	74 participants
		6.01 (23.55)	6.31 (18.70)
Emotional Functional Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		3.68 (24.11)	5.87 (19.39)
Emotional Functional Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		4.69 (26.01)	5.56 (18.68)
Emotional Functional Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		3.47 (26.92)	5.42 (17.91)
Emotional Functional Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		4.54 (26.55)	6.48 (22.00)
Emotional Functional Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		5.35 (28.67)	6.91 (18.66)
Emotional Functional Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		5.82 (28.42)	6.63 (21.00)
Emotional Functional Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		5.28 (26.22)	8.54 (19.57)
Emotional Functional Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		5.93 (25.48)	8.80 (20.89)
Emotional Functional Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		5.44 (27.77)	5.99 (16.15)
Emotional Functional Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		7.56 (28.34)	5.75 (18.51)
Emotional Functional Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		7.08 (25.43)	7.05 (18.96)
Emotional Functional Scale: Change at PT Visit 1	Number Analyzed	177 participants	202 participants
		-5.48 (23.16)	-3.92 (23.28)
Emotional Functional Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-2.64 (23.33)	-4.47 (23.34)
Fatigue Symptom Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	383 participants
		31.96 (23.46)	32.27 (21.92)
Fatigue Symptom Scale: Change at Cycle 2	Number Analyzed	336 participants	343 participants
		3.13 (19.80)	2.32 (21.57)
Fatigue Symptom Scale: Change at Cycle 3	Number Analyzed	322 participants	315 participants
		1.41 (22.65)	3.19 (22.97)
Fatigue Symptom Scale: Change at Cycle 4	Number Analyzed	301 participants	295 participants
		2.77 (23.14)	1.58 (24.04)
Fatigue Symptom Scale: Change at Cycle 5	Number Analyzed	286 participants	288 participants
		3.87 (25.75)	3.05 (24.29)
Fatigue Symptom Scale: Change at Cycle 6	Number Analyzed	272 participants	257 participants
		4.37 (25.64)	2.62 (23.68)
Fatigue Symptom Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		2.36 (26.79)	0.97 (23.44)
Fatigue Symptom Scale: Change at Cycle 8	Number Analyzed	234 participants	217 participants
		-0.19 (25.00)	-1.18 (22.74)
Fatigue Symptom Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		-2.38 (22.69)	-2.01 (22.84)
Fatigue Symptom Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-3.41 (24.69)	-3.08 (22.41)
Fatigue Symptom Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		-4.35 (22.66)	-3.44 (21.21)
Fatigue Symptom Scale: Change at Cycle 12	Number Analyzed	159 participants	140 participants
		-3.14 (24.56)	-4.60 (24.39)
Fatigue Symptom Scale: Change at Cycle 13	Number Analyzed	141 participants	111 participants
		-4.57 (23.31)	-4.50 (21.47)
Fatigue Symptom Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-6.75 (24.32)	-6.54 (22.89)
Fatigue Symptom Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		-5.47 (24.68)	-4.99 (22.40)
Fatigue Symptom Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-3.54 (24.81)	-6.93 (21.89)
Fatigue Symptom Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-4.27 (25.50)	-3.45 (21.91)
Fatigue Symptom Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-4.14 (24.42)	-8.92 (20.54)
Fatigue Symptom Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		-5.32 (27.83)	-9.01 (20.71)
Fatigue Symptom Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-5.56 (26.64)	-6.53 (21.83)
Fatigue Symptom Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		-3.94 (25.97)	-7.41 (23.45)
Fatigue Symptom Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-1.49 (25.58)	-10.64 (22.22)
Fatigue Symptom Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-5.82 (25.23)	-9.60 (28.01)
Fatigue Symptom Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-1.67 (27.05)	-12.50 (24.29)
Fatigue Symptom Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-4.70 (26.16)	-12.35 (22.03)
Fatigue Symptom Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-4.99 (24.85)	-11.46 (22.84)
Fatigue Symptom Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-6.98 (23.76)	-5.36 (23.87)
Fatigue Symptom Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-6.39 (18.98)	-4.70 (26.14)
Fatigue Symptom Scale: Change at PT Visit 1	Number Analyzed	178 participants	202 participants
		10.02 (28.48)	5.25 (24.00)
Fatigue Symptom Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		7.70 (27.65)	9.70 (25.01)
Financial Difficulties Scale: Cycle 1 (Baseline)	Number Analyzed	370 participants	379 participants
		26.67 (30.32)	26.21 (29.78)
Financial Difficulties Scale: Change at Cycle 2	Number Analyzed	332 participants	339 participants
		-0.90 (26.85)	-2.46 (25.46)
Financial Difficulties Scale: Change at Cycle 3	Number Analyzed	320 participants	312 participants
		0.31 (27.62)	0.00 (26.33)
Financial Difficulties Scale: Change at Cycle 4	Number Analyzed	301 participants	292 participants
		0.89 (25.95)	0.11 (25.10)
Financial Difficulties Scale: Change at Cycle 5	Number Analyzed	285 participants	284 participants
		1.75 (27.71)	2.58 (26.46)
Financial Difficulties Scale: Change at Cycle 6	Number Analyzed	270 participants	255 participants
		1.11 (27.62)	0.92 (26.36)
Financial Difficulties Scale: Change at Cycle 7	Number Analyzed	240 participants	224 participants
		1.11 (31.08)	0.30 (26.41)
Financial Difficulties Scale: Change at Cycle 8	Number Analyzed	232 participants	215 participants
		1.15 (30.21)	0.47 (25.27)
Financial Difficulties Scale: Change at Cycle 9	Number Analyzed	210 participants	195 participants
		1.11 (29.78)	-0.51 (24.75)
Financial Difficulties Scale: Change at Cycle 10	Number Analyzed	186 participants	165 participants
		0.90 (30.10)	-2.42 (24.30)
Financial Difficulties Scale: Change at Cycle 11	Number Analyzed	171 participants	154 participants
		0.39 (29.37)	-0.22 (24.84)
Financial Difficulties Scale: Change at Cycle 12	Number Analyzed	159 participants	138 participants
		-1.05 (28.91)	-0.97 (26.39)
Financial Difficulties Scale: Change at Cycle 13	Number Analyzed	140 participants	111 participants
		-0.95 (28.82)	0.30 (24.82)
Financial Difficulties Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-1.73 (29.74)	-0.98 (25.02)
Financial Difficulties Scale: Change at Cycle 15	Number Analyzed	129 participants	98 participants
		-1.81 (28.96)	1.36 (26.18)
Financial Difficulties Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-3.16 (30.13)	0.39 (25.97)
Financial Difficulties Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-3.87 (29.59)	1.35 (27.28)
Financial Difficulties Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-2.29 (27.46)	2.35 (26.02)
Financial Difficulties Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		-0.35 (28.41)	-0.51 (27.73)
Financial Difficulties Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		1.19 (29.47)	1.59 (27.71)
Financial Difficulties Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		1.27 (28.96)	-4.94 (27.78)
Financial Difficulties Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		2.49 (26.79)	-4.26 (23.69)
Financial Difficulties Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-0.53 (26.43)	-2.27 (29.11)
Financial Difficulties Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		1.11 (24.52)	-5.83 (26.03)
Financial Difficulties Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		3.21 (27.42)	-4.63 (25.39)
Financial Difficulties Scale: Change at Cycle 26	Number Analyzed	49 participants	30 participants
		2.72 (28.74)	-2.22 (26.16)
Financial Difficulties Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-3.10 (23.92)	1.15 (24.37)
Financial Difficulties Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-1.67 (23.81)	-1.28 (24.00)
Financial Difficulties Scale: Change at PT Visit 1	Number Analyzed	176 participants	201 participants
		1.70 (29.66)	1.33 (26.21)
Financial Difficulties Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		1.98 (26.17)	4.24 (31.32)
Nausea and Vomiting Scale: Cycle 1 (Baseline)	Number Analyzed	371 participants	383 participants
		11.14 (19.11)	11.92 (18.76)
Nausea And Vomiting Scale: Change at Cycle 2	Number Analyzed	336 participants	343 participants
		5.85 (22.65)	4.08 (22.25)
Nausea And Vomiting Scale: Change at Cycle 3	Number Analyzed	322 participants	316 participants
		5.12 (23.62)	5.06 (21.14)
Nausea And Vomiting Scale: Change at Cycle 4	Number Analyzed	301 participants	295 participants
		4.10 (21.85)	3.56 (23.76)
Nausea And Vomiting Scale: Change at Cycle 5	Number Analyzed	286 participants	288 participants
		5.13 (22.58)	5.15 (23.81)
Nausea And Vomiting Scale: Change at Cycle 6	Number Analyzed	272 participants	257 participants
		4.11 (23.36)	2.59 (21.24)
Nausea And Vomiting Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		2.07 (23.58)	2.49 (22.31)
Nausea And Vomiting Scale: Change at Cycle 8	Number Analyzed	233 participants	217 participants
		-0.86 (20.80)	-0.77 (20.21)
Nausea And Vomiting Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		-2.54 (20.85)	-2.98 (19.78)
Nausea And Vomiting Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-4.30 (18.81)	-2.81 (20.57)
Nausea And Vomiting Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		-3.51 (18.01)	-3.66 (20.04)
Nausea And Vomiting Scale: Change at Cycle 12	Number Analyzed	159 participants	140 participants
		-3.04 (18.07)	-3.45 (20.34)
Nausea And Vomiting Scale: Change at Cycle 13	Number Analyzed	141 participants	111 participants
		-4.02 (16.29)	-3.60 (19.25)
Nausea And Vomiting Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-3.46 (19.54)	-5.72 (18.54)
Nausea And Vomiting Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		-3.59 (16.34)	-3.91 (16.55)
Nausea And Vomiting Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-0.43 (20.32)	-2.55 (20.00)
Nausea And Vomiting Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-0.60 (17.46)	-3.15 (16.48)
Nausea And Vomiting Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-0.65 (16.90)	-3.52 (18.24)
Nausea And Vomiting Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		-0.87 (18.32)	-4.04 (19.62)
Nausea And Vomiting Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-1.79 (18.48)	-3.97 (17.89)
Nausea And Vomiting Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		-1.05 (20.03)	-6.48 (19.80)
Nausea And Vomiting Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-3.48 (19.14)	-8.16 (18.99)
Nausea And Vomiting Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-4.23 (17.70)	-6.44 (24.70)
Nausea And Vomiting Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-4.72 (16.26)	-7.92 (17.70)
Nausea And Vomiting Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-4.17 (20.84)	-7.41 (19.29)
Nausea And Vomiting Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-3.40 (24.29)	-9.38 (19.37)
Nausea And Vomiting Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-5.04 (22.58)	-7.47 (20.70)
Nausea And Vomiting Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-1.25 (20.11)	-6.41 (17.69)
Nausea and Vomiting Scale: Change at PT Visit 1	Number Analyzed	178 participants	202 participants
		4.68 (22.20)	4.13 (23.91)
Nausea and Vomiting Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		4.29 (23.05)	2.73 (21.60)
Pain Symptom Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	383 participants
		23.92 (25.92)	23.72 (24.82)
Pain Symptom Scale: Change at Cycle 2	Number Analyzed	336 participants	342 participants
		-6.80 (24.69)	-6.38 (23.58)
Pain Symptom Scale: Change at Cycle 3	Number Analyzed	322 participants	316 participants
		-9.89 (25.16)	-7.23 (25.78)
Pain Symptom Scale: Change at Cycle 4	Number Analyzed	302 participants	295 participants
		-10.26 (24.78)	-7.46 (26.06)
Pain Symptom Scale: Change at Cycle 5	Number Analyzed	286 participants	288 participants
		-8.86 (25.88)	-6.25 (25.42)
Pain Symptom Scale: Change at Cycle 6	Number Analyzed	272 participants	257 participants
		-8.95 (25.73)	-7.33 (24.85)
Pain Symptom Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		-10.95 (26.13)	-7.46 (24.79)
Pain Symptom Scale: Change at Cycle 8	Number Analyzed	234 participants	217 participants
		-9.97 (25.80)	-8.53 (22.86)
Pain Symptom Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		-9.29 (24.83)	-7.82 (22.98)
Pain Symptom Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-9.41 (26.10)	-8.13 (22.75)
Pain Symptom Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		-10.33 (25.77)	-6.34 (22.97)
Pain Symptom Scale: Change at Cycle 12	Number Analyzed	159 participants	140 participants
		-10.27 (23.10)	-5.24 (25.29)
Pain Symptom Scale: Change at Cycle 13	Number Analyzed	141 participants	111 participants
		-10.28 (25.79)	-4.80 (20.27)
Pain Symptom Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-10.49 (25.49)	-5.56 (23.37)
Pain Symptom Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		-11.15 (22.86)	-3.74 (22.77)
Pain Symptom Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-9.91 (22.94)	-4.71 (23.66)
Pain Symptom Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-7.59 (25.00)	-5.63 (22.63)
Pain Symptom Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-8.82 (23.42)	-8.22 (20.68)
Pain Symptom Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		-8.16 (25.13)	-5.05 (21.48)
Pain Symptom Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-6.94 (25.90)	-6.08 (19.24)
Pain Symptom Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		-9.92 (27.15)	-6.48 (23.44)
Pain Symptom Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-7.71 (26.96)	-8.51 (19.62)
Pain Symptom Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-10.85 (22.03)	-7.95 (26.29)
Pain Symptom Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-10.00 (24.39)	-10.00 (17.21)
Pain Symptom Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-9.94 (24.09)	-12.96 (19.96)
Pain Symptom Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-10.54 (22.49)	-8.33 (18.45)
Pain Symptom Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-11.24 (22.34)	-5.75 (21.95)
Pain Symptom Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-10.42 (27.91)	-9.62 (19.54)
Pain Symptom Scale: Change at PT Visit 1	Number Analyzed	177 participants	202 participants
		1.13 (27.27)	2.06 (28.70)
Pain Symptom Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-1.49 (28.39)	5.45 (29.96)
Physical Functional Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	383 participants
		80.86 (19.53)	82.05 (18.32)
Physical Functional Scale: Change at Cycle 2	Number Analyzed	336 participants	343 participants
		-3.58 (14.56)	-3.01 (15.34)
Physical Functional Scale: Change at Cycle 3	Number Analyzed	322 participants	316 participants
		-2.99 (17.19)	-3.92 (17.03)
Physical Functional Scale: Change at Cycle 4	Number Analyzed	301 participants	294 participants
		-3.28 (18.87)	-3.50 (17.99)
Physical Functional Scale: Change at Cycle 5	Number Analyzed	286 participants	288 participants
		-3.10 (19.35)	-4.62 (17.62)
Physical Functional Scale: Change at Cycle 6	Number Analyzed	272 participants	257 participants
		-5.00 (20.30)	-3.84 (18.65)
Physical Functional Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		-3.66 (20.75)	-3.79 (19.82)
Physical Functional Scale: Change at Cycle 8	Number Analyzed	234 participants	217 participants
		-2.24 (21.14)	-1.56 (18.55)
Physical Functional Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		-1.59 (20.21)	-0.75 (18.44)
Physical Functional Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		0.11 (19.93)	-0.27 (17.16)
Physical Functional Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		0.35 (19.43)	0.27 (17.09)
Physical Functional Scale: Change at Cycle 12	Number Analyzed	159 participants	140 participants
		-1.05 (20.06)	0.89 (16.35)
Physical Functional Scale: Change at Cycle 13	Number Analyzed	141 participants	111 participants
		-0.80 (20.65)	0.27 (17.41)
Physical Functional Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-0.02 (20.14)	1.70 (18.09)
Physical Functional Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		0.41 (18.91)	-0.95 (17.99)
Physical Functional Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-1.08 (19.85)	-0.08 (18.18)
Physical Functional Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-0.46 (19.43)	-0.81 (17.55)
Physical Functional Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		0.13 (19.74)	0.75 (16.85)
Physical Functional Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		1.39 (19.82)	1.31 (14.38)
Physical Functional Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		0.71 (21.08)	0.85 (16.74)
Physical Functional Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		0.42 (22.20)	0.25 (18.18)
Physical Functional Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-2.79 (21.90)	1.42 (16.79)
Physical Functional Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-1.48 (21.47)	0.61 (19.60)
Physical Functional Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-2.67 (22.27)	3.00 (16.47)
Physical Functional Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-2.18 (20.61)	4.81 (15.91)
Physical Functional Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-1.90 (20.09)	-1.88 (20.69)
Physical Functional Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		0.16 (18.66)	-3.68 (19.40)
Physical Functional Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-1.17 (17.79)	-2.82 (18.97)
Physical Functional Scale: Change at PT Visit 1	Number Analyzed	178 participants	202 participants
		-11.37 (23.67)	-7.51 (20.53)
Physical Functional Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-11.49 (24.31)	-11.82 (20.27)
Global Health Status Scale: Cycle 1 (Baseline)	Number Analyzed	370 participants	382 participants
		59.77 (22.88)	59.90 (22.11)
Global Health Status Scale: Change at Cycle 2	Number Analyzed	331 participants	340 participants
		1.81 (23.35)	4.29 (23.42)
Global Health Status Scale: Change at Cycle 3	Number Analyzed	320 participants	315 participants
		1.56 (25.05)	2.86 (25.03)
Global Health Status Scale: Change at Cycle 4	Number Analyzed	300 participants	295 participants
		1.39 (25.26)	4.15 (23.79)
Global Health Status Scale: Change at Cycle 5	Number Analyzed	284 participants	287 participants
		1.17 (25.70)	3.92 (23.05)
Global Health Status Scale: Change at Cycle 6	Number Analyzed	268 participants	256 participants
		0.68 (27.89)	3.61 (23.13)
Global Health Status Scale: Change at Cycle 7	Number Analyzed	241 participants	228 participants
		1.83 (27.81)	3.33 (22.77)
Global Health Status Scale: Change at Cycle 8	Number Analyzed	234 participants	217 participants
		3.06 (27.09)	5.18 (23.18)
Global Health Status Scale: Change at Cycle 9	Number Analyzed	209 participants	196 participants
		4.39 (26.25)	4.68 (22.99)
Global Health Status Scale: Change at Cycle 10	Number Analyzed	184 participants	166 participants
		4.80 (25.35)	5.07 (22.77)
Global Health Status Scale: Change at Cycle 11	Number Analyzed	170 participants	155 participants
		5.78 (26.62)	3.82 (23.75)
Global Health Status Scale: Change at Cycle 12	Number Analyzed	158 participants	139 participants
		3.11 (24.89)	5.34 (24.47)
Global Health Status Scale: Change at Cycle 13	Number Analyzed	140 participants	111 participants
		3.51 (23.82)	3.83 (23.78)
Global Health Status Scale: Change at Cycle 14	Number Analyzed	134 participants	102 participants
		5.97 (23.09)	4.82 (24.86)
Global Health Status Scale: Change at Cycle 15	Number Analyzed	129 participants	98 participants
		4.26 (25.98)	1.70 (24.46)
Global Health Status Scale: Change at Cycle 16	Number Analyzed	115 participants	85 participants
		3.12 (25.16)	3.04 (23.77)
Global Health Status Scale: Change at Cycle 17	Number Analyzed	111 participants	74 participants
		2.93 (24.84)	3.83 (24.84)
Global Health Status Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		3.02 (23.88)	2.58 (27.08)
Global Health Status Scale: Change at Cycle 19	Number Analyzed	95 participants	65 participants
		3.25 (26.39)	3.97 (25.43)
Global Health Status Scale: Change at Cycle 20	Number Analyzed	83 participants	63 participants
		5.12 (24.20)	4.89 (25.69)
Global Health Status Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		5.38 (23.87)	5.40 (24.72)
Global Health Status Scale: Change at Cycle 22	Number Analyzed	66 participants	47 participants
		3.79 (22.56)	3.19 (25.57)
Global Health Status Scale: Change at Cycle 23	Number Analyzed	62 participants	43 participants
		4.03 (23.85)	4.07 (27.18)
Global Health Status Scale: Change at Cycle 24	Number Analyzed	59 participants	40 participants
		4.24 (22.66)	2.92 (30.58)
Global Health Status Scale: Change at Cycle 25	Number Analyzed	51 participants	36 participants
		3.59 (22.38)	8.10 (25.39)
Global Health Status Scale: Change at Cycle 26	Number Analyzed	47 participants	32 participants
		7.27 (24.55)	5.47 (26.91)
Global Health Status Scale: Change at Cycle 27	Number Analyzed	42 participants	29 participants
		7.54 (23.19)	1.72 (28.38)
Global Health Status Scale: Change at Cycle 28	Number Analyzed	39 participants	26 participants
		4.49 (22.69)	4.81 (28.98)
Global Health Status Scale: Change at PT Visit 1	Number Analyzed	176 participants	201 participants
		-7.24 (27.24)	-6.14 (24.97)
Global Health Status Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-2.72 (27.46)	-5.68 (26.57)
Role Functional Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	383 participants
		77.06 (27.02)	79.33 (25.12)
Role Functional Scale: Change at Cycle 2	Number Analyzed	335 participants	343 participants
		-3.78 (24.99)	-2.82 (24.35)
Role Functional Scale: Change at Cycle 3	Number Analyzed	322 participants	315 participants
		-3.62 (25.96)	-4.55 (28.00)
Role Functional Scale: Change at Cycle 4	Number Analyzed	302 participants	295 participants
		-4.64 (27.69)	-5.99 (26.87)
Role Functional Scale: Change at Cycle 5	Number Analyzed	286 participants	288 participants
		-4.72 (27.68)	-7.41 (27.25)
Role Functional Scale: Change at Cycle 6	Number Analyzed	272 participants	257 participants
		-6.13 (28.94)	-6.03 (28.51)
Role Functional Scale: Change at Cycle 7	Number Analyzed	242 participants	228 participants
		-4.82 (29.75)	-5.34 (26.31)
Role Functional Scale: Change at Cycle 8	Number Analyzed	234 participants	217 participants
		-1.85 (28.87)	-2.38 (26.41)
Role Functional Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		-1.19 (28.57)	-2.47 (27.29)
Role Functional Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-1.79 (28.10)	0.90 (25.97)
Role Functional Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		-0.78 (28.34)	-2.69 (24.94)
Role Functional Scale: Change at Cycle 12	Number Analyzed	159 participants	140 participants
		-1.05 (27.28)	0.24 (24.07)
Role Functional Scale: Change at Cycle 13	Number Analyzed	141 participants	111 participants
		-2.01 (26.61)	-2.40 (24.91)
Role Functional Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-0.86 (27.27)	-1.31 (25.66)
Role Functional Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		-1.03 (27.51)	-3.23 (25.40)
Role Functional Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-3.16 (28.73)	-2.35 (25.48)
Role Functional Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-1.04 (26.69)	-3.38 (25.88)
Role Functional Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-0.16 (27.10)	0.23 (26.05)
Role Functional Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		1.04 (27.55)	-0.25 (23.48)
Role Functional Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-1.19 (30.04)	0.79 (23.46)
Role Functional Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		-0.84 (28.98)	0.00 (27.47)
Role Functional Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-2.24 (27.96)	1.06 (22.63)
Role Functional Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-3.44 (30.11)	1.14 (25.01)
Role Functional Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-4.44 (29.73)	2.08 (24.22)
Role Functional Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-3.53 (29.21)	4.63 (26.91)
Role Functional Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-1.36 (28.02)	0.52 (26.60)
Role Functional Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-1.55 (30.82)	-4.02 (29.77)
Role Functional Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-0.42 (27.86)	-3.85 (29.56)
Role Functional Scale: Change at PT Visit 1	Number Analyzed	178 participants	202 participants
		-14.61 (30.41)	-9.49 (28.64)
Role Functional Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-10.73 (31.94)	-15.45 (31.82)
Social Functional Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	381 participants
		77.96 (24.09)	75.90 (24.69)
Social Functional Scale: Change at Cycle 2	Number Analyzed	333 participants	341 participants
		-3.45 (24.07)	-0.44 (23.09)
Social Functional Scale: Change at Cycle 3	Number Analyzed	321 participants	314 participants
		-4.62 (25.25)	-2.07 (25.35)
Social Functional Scale: Change at Cycle 4	Number Analyzed	302 participants	294 participants
		-2.59 (25.08)	-1.70 (26.58)
Social Functional Scale: Change at Cycle 5	Number Analyzed	286 participants	286 participants
		-5.54 (27.03)	-3.26 (27.24)
Social Functional Scale: Change at Cycle 6	Number Analyzed	271 participants	256 participants
		-5.72 (27.87)	-1.04 (27.20)
Social Functional Scale: Change at Cycle 7	Number Analyzed	242 participants	227 participants
		-2.69 (27.13)	-0.15 (26.00)
Social Functional Scale: Change at Cycle 8	Number Analyzed	233 participants	216 participants
		-1.72 (26.93)	1.08 (26.49)
Social Functional Scale: Change at Cycle 9	Number Analyzed	210 participants	196 participants
		0.56 (27.59)	0.77 (25.11)
Social Functional Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-0.81 (27.31)	2.31 (25.75)
Social Functional Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		0.58 (27.35)	1.94 (24.39)
Social Functional Scale: Change at Cycle 12	Number Analyzed	159 participants	139 participants
		0.52 (28.59)	2.40 (24.70)
Social Functional Scale: Change at Cycle 13	Number Analyzed	140 participants	111 participants
		0.83 (25.31)	2.10 (25.73)
Social Functional Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		1.98 (26.71)	2.12 (24.89)
Social Functional Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		1.79 (27.24)	0.00 (27.08)
Social Functional Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-0.72 (25.76)	0.39 (25.84)
Social Functional Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-0.45 (26.51)	1.58 (24.39)
Social Functional Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-0.98 (25.99)	2.11 (26.42)
Social Functional Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		2.26 (26.56)	3.28 (21.53)
Social Functional Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		1.59 (27.09)	0.79 (22.88)
Social Functional Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		1.27 (28.09)	5.86 (22.00)
Social Functional Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		1.24 (27.72)	2.84 (24.16)
Social Functional Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		6.08 (27.32)	1.89 (22.51)
Social Functional Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		5.83 (25.64)	4.17 (24.39)
Social Functional Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		1.60 (27.27)	2.78 (23.40)
Social Functional Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		3.74 (26.19)	1.56 (24.45)
Social Functional Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		5.81 (24.37)	-1.72 (26.85)
Social Functional Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		6.25 (23.48)	-0.64 (24.26)
Social Functional Scale: Change at PT Visit 1	Number Analyzed	177 participants	202 participants
		-9.13 (26.47)	-3.80 (28.74)
Social Functional Scale: Change at PT Visit 2	Number Analyzed	101 participants	110 participants
		-5.45 (28.49)	-8.48 (28.98)
Insomnia Symptom Scale: Cycle 1 (Baseline)	Number Analyzed	372 participants	383 participants
		22.94 (28.00)	25.41 (28.81)
Insomnia Symptom Scale: Change at Cycle 2	Number Analyzed	336 participants	343 participants
		-0.69 (26.82)	-0.39 (28.27)
Insomnia Symptom Scale: Change at Cycle 3	Number Analyzed	321 participants	316 participants
		-3.53 (27.03)	-3.48 (30.14)
Insomnia Symptom Scale: Change at Cycle 4	Number Analyzed	301 participants	295 participants
		-2.88 (28.14)	-3.62 (30.40)
Insomnia Symptom Scale: Change at Cycle 5	Number Analyzed	286 participants	288 participants
		-2.21 (29.27)	-2.66 (30.17)
Insomnia Symptom Scale: Change at Cycle 6	Number Analyzed	272 participants	257 participants
		-2.94 (28.63)	-5.58 (32.53)
Insomnia Symptom Scale: Change at Cycle 7	Number Analyzed	241 participants	228 participants
		-4.56 (28.42)	-4.82 (32.98)
Insomnia Symptom Scale: Change at Cycle 8	Number Analyzed	234 participants	217 participants
		-6.13 (27.72)	-6.45 (30.75)
Insomnia Symptom Scale: Change at Cycle 9	Number Analyzed	208 participants	196 participants
		-8.97 (25.69)	-6.12 (30.32)
Insomnia Symptom Scale: Change at Cycle 10	Number Analyzed	186 participants	166 participants
		-8.24 (26.69)	-4.42 (28.79)
Insomnia Symptom Scale: Change at Cycle 11	Number Analyzed	171 participants	155 participants
		-8.97 (28.19)	-5.81 (27.69)
Insomnia Symptom Scale: Change at Cycle 12	Number Analyzed	159 participants	140 participants
		-8.81 (27.67)	-6.43 (26.49)
Insomnia Symptom Scale: Change at Cycle 13	Number Analyzed	141 participants	111 participants
		-10.17 (26.71)	-5.11 (24.29)
Insomnia Symptom Scale: Change at Cycle 14	Number Analyzed	135 participants	102 participants
		-9.14 (26.84)	-7.84 (24.45)
Insomnia Symptom Scale: Change at Cycle 15	Number Analyzed	130 participants	98 participants
		-9.74 (28.89)	-5.10 (21.59)
Insomnia Symptom Scale: Change at Cycle 16	Number Analyzed	116 participants	85 participants
		-8.91 (26.14)	-4.31 (26.62)
Insomnia Symptom Scale: Change at Cycle 17	Number Analyzed	112 participants	74 participants
		-11.01 (26.62)	-5.41 (26.48)
Insomnia Symptom Scale: Change at Cycle 18	Number Analyzed	102 participants	71 participants
		-8.82 (28.12)	-8.45 (20.09)
Insomnia Symptom Scale: Change at Cycle 19	Number Analyzed	96 participants	66 participants
		-11.46 (29.35)	-7.58 (22.49)
Insomnia Symptom Scale: Change at Cycle 20	Number Analyzed	84 participants	63 participants
		-10.32 (27.37)	-5.29 (25.55)
Insomnia Symptom Scale: Change at Cycle 21	Number Analyzed	79 participants	54 participants
		-11.81 (27.24)	-4.94 (27.02)
Insomnia Symptom Scale: Change at Cycle 22	Number Analyzed	67 participants	47 participants
		-10.95 (31.46)	-7.80 (19.92)
Insomnia Symptom Scale: Change at Cycle 23	Number Analyzed	63 participants	44 participants
		-10.58 (34.82)	-6.06 (23.04)
Insomnia Symptom Scale: Change at Cycle 24	Number Analyzed	60 participants	40 participants
		-9.44 (31.94)	-7.50 (21.99)
Insomnia Symptom Scale: Change at Cycle 25	Number Analyzed	52 participants	36 participants
		-10.26 (28.42)	-8.33 (26.87)
Insomnia Symptom Scale: Change at Cycle 26	Number Analyzed	49 participants	32 participants
		-9.52 (32.63)	-4.17 (20.30)
Insomnia Symptom Scale: Change at Cycle 27	Number Analyzed	43 participants	29 participants
		-13.18 (30.11)	-4.60 (19.36)
Insomnia Symptom Scale: Change at Cycle 28	Number Analyzed	40 participants	26 participants
		-11.67 (31.62)	-1.28 (22.07)
Insomnia Symptom Scale: Change at PT Visit 1	Number Analyzed	178 participants	202 participants
		2.81 (29.19)	-1.32 (30.81)
Insomnia Symptom Scale: Change at PT Visit 2	Number Analyzed	100 participants	110 participants
		5.67 (29.23)	3.03 (31.13)

10. Secondary Outcome

Title	Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score
Description	The EORTC QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). The questions are grouped into five scales and 4 single items which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms. A positive value means an increase, while a negative values means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).
Time Frame	Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)

Outcome Measure Data

Analysis Population Description

Participants in the ITT population (includes all randomized participants, regardless of whether study medication was received) with both a baseline assessment and at least 1 post-treatment assessment are included in the analysis.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed		388	392
Mean (Standard Deviation); Unit of Measure: score on a scale
Anxiety: Cycle 1 (Baseline)	Number Analyzed	366 participants	373 participants
		40.10 (25.85)	40.48 (25.32)
Anxiety: Change at Cycle 2	Number Analyzed	329 participants	334 participants
		-2.58 (21.72)	-4.11 (21.19)
Anxiety: Change at Cycle 3	Number Analyzed	317 participants	309 participants
		-4.14 (22.45)	-3.87 (23.19)
Anxiety: Change at Cycle 4	Number Analyzed	295 participants	289 participants
		-4.52 (23.01)	-7.25 (23.16)
Anxiety: Change at Cycle 5	Number Analyzed	282 participants	285 participants
		-4.10 (22.94)	-7.39 (24.36)
Anxiety: Change at Cycle 6	Number Analyzed	269 participants	252 participants
		-4.54 (23.97)	-8.42 (25.21)
Anxiety: Change at Cycle 7	Number Analyzed	238 participants	226 participants
		-6.40 (24.00)	-10.40 (24.37)
Anxiety: Change at Cycle 8	Number Analyzed	232 participants	213 participants
		-9.00 (23.17)	-11.92 (24.50)
Anxiety: Change at Cycle 9	Number Analyzed	206 participants	193 participants
		-10.09 (23.30)	-11.43 (23.24)
Anxiety: Change at Cycle 10	Number Analyzed	185 participants	164 participants
		-11.17 (25.05)	-12.64 (22.09)
Anxiety: Change at Cycle 11	Number Analyzed	168 participants	153 participants
		-10.78 (23.47)	-12.09 (21.84)
Anxiety: Change at Cycle 12	Number Analyzed	158 participants	138 participants
		-12.62 (26.24)	-13.16 (23.11)
Anxiety: Change at Cycle 13	Number Analyzed	141 participants	110 participants
		-13.32 (25.93)	-13.33 (22.47)
Anxiety: Change at Cycle 14	Number Analyzed	135 participants	101 participants
		-14.32 (26.49)	-12.43 (23.59)
Anxiety: Change at Cycle 15	Number Analyzed	130 participants	96 participants
		-13.42 (26.64)	-10.65 (25.74)
Anxiety: Change at Cycle 16	Number Analyzed	115 participants	84 participants
		-12.75 (26.87)	-12.57 (23.89)
Anxiety: Change at Cycle 17	Number Analyzed	111 participants	73 participants
		-13.41 (27.30)	-12.79 (21.01)
Anxiety: Change at Cycle 18	Number Analyzed	101 participants	70 participants
		-13.53 (28.05)	-12.38 (22.90)
Anxiety: Change at Cycle 19	Number Analyzed	95 participants	65 participants
		-14.50 (27.41)	-12.48 (20.08)
Anxiety: Change at Cycle 20	Number Analyzed	84 participants	62 participants
		-15.34 (29.21)	-12.37 (23.73)
Anxiety: Change at Cycle 21	Number Analyzed	79 participants	53 participants
		-16.03 (28.84)	-14.47 (25.00)
Anxiety: Change at Cycle 22	Number Analyzed	66 participants	46 participants
		-13.30 (30.77)	-15.46 (23.83)
Anxiety: Change at Cycle 23	Number Analyzed	63 participants	43 participants
		-17.28 (30.64)	-14.47 (29.55)
Anxiety: Change at Cycle 24	Number Analyzed	60 participants	39 participants
		-16.11 (30.65)	-17.09 (23.76)
Anxiety: Change at Cycle 25	Number Analyzed	52 participants	35 participants
		-16.03 (29.47)	-17.78 (23.68)
Anxiety: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		-19.73 (30.28)	-13.26 (22.11)
Anxiety: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		-21.71 (29.89)	-12.70 (20.67)
Anxiety: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		-22.51 (29.34)	-12.89 (22.38)
Anxiety: Change at PT Visit 1	Number Analyzed	175 participants	196 participants
		-0.73 (25.18)	-4.73 (27.21)
Anxiety: Change at PT Visit 2	Number Analyzed	99 participants	106 participants
		-4.04 (28.24)	-3.98 (25.02)
Body Image: Cycle 1 (Baseline)	Number Analyzed	364 participants	373 participants
		23.53 (28.40)	23.68 (27.47)
Body Image: Change at Cycle 2	Number Analyzed	326 participants	334 participants
		1.33 (28.19)	1.20 (26.44)
Body Image: Change at Cycle 3	Number Analyzed	316 participants	309 participants
		1.48 (29.06)	3.88 (28.03)
Body Image: Change at Cycle 4	Number Analyzed	294 participants	289 participants
		4.20 (28.51)	1.15 (27.19)
Body Image: Change at Cycle 5	Number Analyzed	280 participants	284 participants
		2.86 (30.91)	1.06 (25.74)
Body Image: Change at Cycle 6	Number Analyzed	268 participants	252 participants
		0.75 (30.11)	2.78 (28.48)
Body Image: Change at Cycle 7	Number Analyzed	237 participants	226 participants
		-0.56 (28.94)	0.29 (25.53)
Body Image: Change at Cycle 8	Number Analyzed	230 participants	213 participants
		-1.74 (29.83)	0.00 (26.30)
Body Image: Change at Cycle 9	Number Analyzed	205 participants	193 participants
		-3.58 (28.74)	-0.69 (24.52)
Body Image: Change at Cycle 10	Number Analyzed	184 participants	164 participants
		-5.07 (30.15)	-3.25 (24.55)
Body Image: Change at Cycle 11	Number Analyzed	166 participants	153 participants
		-4.62 (30.24)	-1.53 (25.46)
Body Image: Change at Cycle 12	Number Analyzed	157 participants	138 participants
		-5.31 (31.92)	-2.66 (27.04)
Body Image: Change at Cycle 13	Number Analyzed	141 participants	110 participants
		-4.73 (30.23)	-2.73 (25.99)
Body Image: Change at Cycle 14	Number Analyzed	135 participants	101 participants
		-5.43 (29.70)	-4.62 (24.05)
Body Image: Change at Cycle 15	Number Analyzed	130 participants	96 participants
		-3.08 (30.63)	-2.43 (27.03)
Body Image: Change at Cycle 16	Number Analyzed	115 participants	84 participants
		-1.74 (32.99)	-1.19 (26.10)
Body Image: Change at Cycle 17	Number Analyzed	111 participants	73 participants
		-2.70 (32.76)	-2.28 (21.75)
Body Image: Change at Cycle 18	Number Analyzed	101 participants	70 participants
		-2.64 (30.44)	-5.71 (23.38)
Body Image: Change at Cycle 19	Number Analyzed	95 participants	64 participants
		-2.81 (33.57)	-5.21 (20.76)
Body Image: Change at Cycle 20	Number Analyzed	84 participants	62 participants
		-3.97 (30.79)	-5.38 (22.74)
Body Image: Change at Cycle 21	Number Analyzed	79 participants	53 participants
		1.69 (30.15)	-8.18 (26.07)
Body Image: Change at Cycle 22	Number Analyzed	67 participants	46 participants
		-1.49 (32.01)	-10.87 (22.28)
Body Image: Change at Cycle 23	Number Analyzed	63 participants	43 participants
		-5.82 (24.35)	-8.53 (29.18)
Body Image: Change at Cycle 24	Number Analyzed	59 participants	39 participants
		-0.56 (31.25)	-11.11 (23.36)
Body Image: Change at Cycle 25	Number Analyzed	52 participants	35 participants
		-3.21 (28.97)	-11.43 (24.18)
Body Image: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		-4.76 (29.66)	-6.45 (18.09)
Body Image: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		0.78 (24.65)	-7.14 (21.00)
Body Image: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		-4.27 (26.69)	-4.00 (24.19)
Body Image: Change at PT Visit 1	Number Analyzed	175 participants	195 participants
		2.48 (31.57)	3.42 (29.31)
Body Image: Change at PT Visit 2	Number Analyzed	99 participants	105 participants
		2.36 (35.40)	6.35 (27.38)
Dry Mouth: Cycle 1 (Baseline)	Number Analyzed	367 participants	373 participants
		21.80 (25.07)	23.32 (26.79)
Dry Mouth: Change at Cycle 2	Number Analyzed	328 participants	333 participants
		7.72 (28.70)	3.00 (25.43)
Dry Mouth: Change at Cycle 3	Number Analyzed	317 participants	308 participants
		6.10 (28.65)	4.87 (27.33)
Dry Mouth: Change at Cycle 4	Number Analyzed	294 participants	288 participants
		4.76 (29.40)	2.66 (31.06)
Dry Mouth: Change at Cycle 5	Number Analyzed	283 participants	285 participants
		2.47 (29.67)	2.57 (28.68)
Dry Mouth: Change at Cycle 6	Number Analyzed	270 participants	252 participants
		2.96 (30.14)	1.19 (27.65)
Dry Mouth: Change at Cycle 7	Number Analyzed	238 participants	226 participants
		-1.96 (28.82)	0.44 (28.54)
Dry Mouth: Change at Cycle 8	Number Analyzed	233 participants	213 participants
		-2.43 (28.68)	-2.66 (26.27)
Dry Mouth: Change at Cycle 9	Number Analyzed	207 participants	193 participants
		-3.70 (25.70)	-4.32 (24.74)
Dry Mouth: Change at Cycle 10	Number Analyzed	186 participants	164 participants
		-6.27 (25.04)	-3.46 (23.53)
Dry Mouth: Change at Cycle 11	Number Analyzed	169 participants	153 participants
		-7.69 (25.46)	-1.96 (26.56)
Dry Mouth: Change at Cycle 12	Number Analyzed	159 participants	138 participants
		-8.18 (24.22)	-4.35 (26.36)
Dry Mouth: Change at Cycle 13	Number Analyzed	141 participants	110 participants
		-9.69 (24.08)	-8.48 (26.50)
Dry Mouth: Change at Cycle 14	Number Analyzed	136 participants	101 participants
		-8.33 (24.60)	-3.63 (29.78)
Dry Mouth: Change at Cycle 15	Number Analyzed	131 participants	96 participants
		-7.89 (22.20)	-7.29 (26.58)
Dry Mouth: Change at Cycle 16	Number Analyzed	116 participants	84 participants
		-6.32 (24.44)	-8.33 (27.80)
Dry Mouth: Change at Cycle 17	Number Analyzed	112 participants	73 participants
		-7.44 (23.12)	-3.20 (24.32)
Dry Mouth: Change at Cycle 18	Number Analyzed	102 participants	70 participants
		-5.56 (24.86)	-8.10 (28.62)
Dry Mouth: Change at Cycle 19	Number Analyzed	96 participants	65 participants
		-5.90 (24.18)	-7.69 (25.53)
Dry Mouth: Change at Cycle 20	Number Analyzed	84 participants	62 participants
		-6.35 (26.62)	-9.68 (27.25)
Dry Mouth: Change at Cycle 21	Number Analyzed	79 participants	53 participants
		-7.17 (24.27)	-9.43 (20.02)
Dry Mouth: Change at Cycle 22	Number Analyzed	67 participants	46 participants
		-3.98 (26.29)	-8.70 (23.76)
Dry Mouth: Change at Cycle 23	Number Analyzed	63 participants	43 participants
		-7.94 (23.73)	-3.88 (25.42)
Dry Mouth: Change at Cycle 24	Number Analyzed	60 participants	39 participants
		-6.67 (25.15)	-9.40 (28.56)
Dry Mouth: Change at Cycle 25	Number Analyzed	52 participants	35 participants
		-8.33 (22.75)	-9.52 (28.66)
Dry Mouth: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		-2.72 (23.41)	-7.53 (26.82)
Dry Mouth: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		-6.98 (21.28)	-7.14 (27.75)
Dry Mouth: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		-8.55 (21.24)	-8.00 (22.11)
Dry Mouth: Change at PT Visit 1	Number Analyzed	175 participants	196 participants
		0.19 (28.70)	2.38 (31.58)
Dry Mouth: Change at PT Visit 2	Number Analyzed	99 participants	106 participants
		-1.35 (30.09)	1.89 (25.95)
Dysphagia: Cycle 1 (Baseline)	Number Analyzed	367 participants	373 participants
		16.29 (21.46)	14.15 (18.93)
Dysphagia: Change at Cycle 2	Number Analyzed	330 participants	334 participants
		-2.27 (17.64)	-0.53 (19.32)
Dysphagia: Change at Cycle 3	Number Analyzed	318 participants	308 participants
		-3.39 (18.57)	-2.15 (19.67)
Dysphagia: Change at Cycle 4	Number Analyzed	295 participants	289 participants
		-2.94 (18.93)	-1.08 (18.79)
Dysphagia: Change at Cycle 5	Number Analyzed	283 participants	285 participants
		-3.22 (19.92)	-1.83 (18.99)
Dysphagia: Change at Cycle 6	Number Analyzed	270 participants	252 participants
		-4.20 (18.99)	-2.25 (18.70)
Dysphagia: Change at Cycle 7	Number Analyzed	239 participants	226 participants
		-4.83 (20.56)	-1.97 (19.94)
Dysphagia: Change at Cycle 8	Number Analyzed	233 participants	213 participants
		-5.96 (18.80)	-3.29 (18.48)
Dysphagia: Change at Cycle 9	Number Analyzed	207 participants	193 participants
		-6.17 (18.21)	-3.86 (18.49)
Dysphagia: Change at Cycle 10	Number Analyzed	186 participants	164 participants
		-6.03 (17.37)	-4.61 (16.87)
Dysphagia: Change at Cycle 11	Number Analyzed	169 participants	153 participants
		-6.25 (17.09)	-2.83 (17.03)
Dysphagia: Change at Cycle 12	Number Analyzed	159 participants	138 participants
		-7.06 (17.65)	-4.19 (15.84)
Dysphagia: Change at Cycle 13	Number Analyzed	141 participants	110 participants
		-6.93 (18.71)	-3.54 (17.61)
Dysphagia: Change at Cycle 14	Number Analyzed	136 participants	101 participants
		-8.01 (18.53)	-4.95 (18.22)
Dysphagia: Change at Cycle 15	Number Analyzed	131 participants	96 participants
		-6.45 (17.38)	-2.14 (18.69)
Dysphagia: Change at Cycle 16	Number Analyzed	116 participants	84 participants
		-4.41 (18.29)	-3.70 (21.08)
Dysphagia: Change at Cycle 17	Number Analyzed	112 participants	73 participants
		-5.36 (16.87)	-3.20 (14.99)
Dysphagia: Change at Cycle 18	Number Analyzed	102 participants	70 participants
		-4.90 (16.44)	-3.33 (19.78)
Dysphagia: Change at Cycle 19	Number Analyzed	96 participants	65 participants
		-4.40 (17.10)	-3.59 (14.31)
Dysphagia: Change at Cycle 20	Number Analyzed	84 participants	62 participants
		-2.51 (16.21)	-3.76 (15.83)
Dysphagia: Change at Cycle 21	Number Analyzed	79 participants	53 participants
		-3.80 (19.24)	-2.10 (17.84)
Dysphagia: Change at Cycle 22	Number Analyzed	67 participants	46 participants
		-3.65 (20.41)	-4.83 (15.65)
Dysphagia: Change at Cycle 23	Number Analyzed	63 participants	43 participants
		-4.23 (18.87)	-3.88 (17.63)
Dysphagia: Change at Cycle 24	Number Analyzed	60 participants	39 participants
		-5.00 (18.35)	-3.70 (13.08)
Dysphagia: Change at Cycle 25	Number Analyzed	52 participants	35 participants
		-5.98 (19.61)	-2.22 (16.79)
Dysphagia: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		-5.67 (20.43)	-2.87 (16.22)
Dysphagia: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		-5.68 (20.91)	-4.37 (12.22)
Dysphagia: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		-8.26 (19.86)	-3.56 (11.44)
Dysphagia: Change at PT Visit 1	Number Analyzed	176 participants	196 participants
		0.44 (24.15)	2.83 (22.63)
Dysphagia: Change at PT Visit 2	Number Analyzed	99 participants	106 participants
		-2.81 (24.40)	3.25 (19.81)
Eating Restrictions: Cycle 1 (Baseline)	Number Analyzed	366 participants	373 participants
		23.26 (21.78)	22.33 (20.22)
Eating Restrictions: Change at Cycle 2	Number Analyzed	328 participants	334 participants
		-1.41 (19.36)	-1.54 (19.62)
Eating Restrictions: Change at Cycle 3	Number Analyzed	318 participants	308 participants
		-1.04 (21.09)	-2.20 (20.94)
Eating Restrictions: Change at Cycle 4	Number Analyzed	295 participants	289 participants
		-2.24 (20.81)	-1.39 (23.36)
Eating Restrictions: Change at Cycle 5	Number Analyzed	283 participants	285 participants
		-1.39 (22.10)	-0.09 (23.31)
Eating Restrictions: Change at Cycle 6	Number Analyzed	270 participants	252 participants
		-1.35 (22.77)	-3.32 (23.14)
Eating Restrictions: Change at Cycle 7	Number Analyzed	239 participants	225 participants
		-2.45 (22.68)	-2.67 (21.66)
Eating Restrictions: Change at Cycle 8	Number Analyzed	233 participants	213 participants
		-4.29 (22.70)	-5.56 (19.87)
Eating Restrictions: Change at Cycle 9	Number Analyzed	207 participants	193 participants
		-6.99 (21.16)	-6.48 (19.69)
Eating Restrictions: Change at Cycle 10	Number Analyzed	186 participants	164 participants
		-7.06 (21.32)	-5.89 (19.30)
Eating Restrictions: Change at Cycle 11	Number Analyzed	169 participants	153 participants
		-8.22 (21.25)	-5.05 (19.98)
Eating Restrictions: Change at Cycle 12	Number Analyzed	159 participants	138 participants
		-7.74 (21.16)	-6.34 (19.87)
Eating Restrictions: Change at Cycle 13	Number Analyzed	141 participants	110 participants
		-8.55 (20.41)	-8.41 (19.57)
Eating Restrictions: Change at Cycle 14	Number Analyzed	136 participants	101 participants
		-8.62 (19.16)	-8.58 (21.16)
Eating Restrictions: Change at Cycle 15	Number Analyzed	131 participants	96 participants
		-6.85 (20.92)	-5.56 (21.21)
Eating Restrictions: Change at Cycle 16	Number Analyzed	116 participants	84 participants
		-5.77 (22.01)	-6.94 (20.36)
Eating Restrictions: Change at Cycle 17	Number Analyzed	112 participants	73 participants
		-5.56 (21.95)	-7.42 (17.76)
Eating Restrictions: Change at Cycle 18	Number Analyzed	102 participants	70 participants
		-7.27 (20.40)	-6.90 (21.14)
Eating Restrictions: Change at Cycle 19	Number Analyzed	96 participants	65 participants
		-7.03 (21.78)	-5.38 (18.07)
Eating Restrictions: Change at Cycle 20	Number Analyzed	84 participants	62 participants
		-4.56 (21.03)	-4.44 (16.72)
Eating Restrictions: Change at Cycle 21	Number Analyzed	79 participants	53 participants
		-5.80 (22.58)	-5.03 (19.97)
Eating Restrictions: Change at Cycle 22	Number Analyzed	67 participants	46 participants
		-3.65 (21.79)	-6.16 (16.80)
Eating Restrictions: Change at Cycle 23	Number Analyzed	63 participants	43 participants
		-3.70 (22.74)	-5.23 (20.25)
Eating Restrictions: Change at Cycle 24	Number Analyzed	60 participants	39 participants
		-5.00 (20.77)	-7.91 (15.76)
Eating Restrictions: Change at Cycle 25	Number Analyzed	52 participants	35 participants
		-5.77 (21.10)	-5.95 (16.61)
Eating Restrictions: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		-6.80 (21.22)	-2.42 (22.89)
Eating Restrictions: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		-5.62 (23.48)	-3.87 (10.26)
Eating Restrictions: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		-7.91 (21.79)	-5.00 (11.02)
Eating Restrictions: Change at PT Visit 1	Number Analyzed	176 participants	196 participants
		1.52 (24.48)	0.94 (24.70)
Eating Restrictions: Change at PT Visit 2	Number Analyzed	99 participants	106 participants
		-2.10 (25.32)	0.94 (21.46)
Hair Loss: Cycle 1 (Baseline)	Number Analyzed	363 participants	371 participants
		4.73 (13.28)	4.04 (13.20)
Hair Loss: Change at Cycle 2	Number Analyzed	326 participants	329 participants
		0.20 (14.85)	1.27 (16.59)
Hair Loss: Change at Cycle 3	Number Analyzed	315 participants	306 participants
		4.34 (17.51)	4.52 (18.71)
Hair Loss: Change at Cycle 4	Number Analyzed	293 participants	286 participants
		5.40 (18.46)	6.53 (20.99)
Hair Loss: Change at Cycle 5	Number Analyzed	278 participants	281 participants
		6.12 (19.38)	7.18 (19.49)
Hair Loss: Change at Cycle 6	Number Analyzed	267 participants	250 participants
		6.93 (18.87)	10.07 (22.94)
Hair Loss: Change at Cycle 7	Number Analyzed	236 participants	225 participants
		5.72 (19.91)	9.26 (22.92)
Hair Loss: Change at Cycle 8	Number Analyzed	230 participants	210 participants
		5.00 (18.96)	7.38 (23.05)
Hair Loss: Change at Cycle 9	Number Analyzed	203 participants	191 participants
		2.38 (17.43)	6.46 (21.06)
Hair Loss: Change at Cycle 10	Number Analyzed	183 participants	162 participants
		0.64 (16.88)	4.22 (19.51)
Hair Loss: Change at Cycle 11	Number Analyzed	165 participants	151 participants
		-0.10 (17.02)	2.54 (17.51)
Hair Loss: Change at Cycle 12	Number Analyzed	157 participants	136 participants
		0.21 (19.70)	1.96 (15.72)
Hair Loss: Change at Cycle 13	Number Analyzed	140 participants	109 participants
		0.36 (18.91)	2.29 (15.46)
Hair Loss: Change at Cycle 14	Number Analyzed	134 participants	100 participants
		-1.37 (17.59)	1.83 (15.15)
Hair Loss: Change at Cycle 15	Number Analyzed	129 participants	95 participants
		-0.39 (15.65)	1.58 (12.65)
Hair Loss: Change at Cycle 16	Number Analyzed	113 participants	82 participants
		-1.47 (17.47)	1.42 (13.91)
Hair Loss: Change at Cycle 17	Number Analyzed	109 participants	73 participants
		-1.07 (17.75)	0.23 (12.57)
Hair Loss: Change at Cycle 18	Number Analyzed	99 participants	70 participants
		-1.68 (17.58)	-0.71 (13.14)
Hair Loss: Change at Cycle 19	Number Analyzed	93 participants	65 participants
		-0.90 (18.12)	0.51 (14.12)
Hair Loss: Change at Cycle 20	Number Analyzed	83 participants	62 participants
		-0.20 (19.21)	-1.61 (12.70)
Hair Loss: Change at Cycle 21	Number Analyzed	78 participants	53 participants
		-1.07 (19.43)	-1.57 (8.81)
Hair Loss: Change at Cycle 22	Number Analyzed	67 participants	46 participants
		-0.50 (16.66)	-3.26 (11.98)
Hair Loss: Change at Cycle 23	Number Analyzed	62 participants	42 participants
		-0.54 (16.79)	-1.19 (11.28)
Hair Loss: Change at Cycle 24	Number Analyzed	60 participants	39 participants
		-1.39 (17.44)	1.71 (16.13)
Hair Loss: Change at Cycle 25	Number Analyzed	51 participants	35 participants
		-1.96 (18.75)	-0.95 (9.85)
Hair Loss: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		-1.02 (19.37)	-0.54 (10.08)
Hair Loss: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		-3.10 (15.96)	-0.60 (10.62)
Hair Loss: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		-4.70 (20.57)	-1.33 (10.67)
Hair Loss: Change at PT Visit 1	Number Analyzed	174 participants	192 participants
		4.98 (19.73)	4.51 (20.39)
Hair Loss: Change at PT Visit 2	Number Analyzed	99 participants	105 participants
		15.82 (25.35)	22.22 (30.81)
Pain: Cycle 1 (Baseline)	Number Analyzed	367 participants	373 participants
		26.48 (21.34)	26.47 (20.70)
Pain: Change at Cycle 2	Number Analyzed	330 participants	334 participants
		-4.63 (20.30)	-5.86 (19.15)
Pain: Change at Cycle 3	Number Analyzed	318 participants	308 participants
		-6.96 (20.37)	-5.86 (20.68)
Pain: Change at Cycle 4	Number Analyzed	296 participants	289 participants
		-6.45 (21.47)	-7.48 (21.23)
Pain: Change at Cycle 5	Number Analyzed	283 participants	285 participants
		-7.28 (20.95)	-6.89 (22.10)
Pain: Change at Cycle 6	Number Analyzed	270 participants	252 participants
		-7.24 (20.84)	-7.22 (21.62)
Pain: Change at Cycle 7	Number Analyzed	239 participants	226 participants
		-9.52 (21.18)	-6.62 (21.63)
Pain: Change at Cycle 8	Number Analyzed	233 participants	213 participants
		-10.53 (21.62)	-8.16 (20.11)
Pain: Change at Cycle 9	Number Analyzed	207 participants	193 participants
		-10.08 (19.60)	-8.98 (20.29)
Pain: Change at Cycle 10	Number Analyzed	186 participants	164 participants
		-10.63 (19.23)	-8.59 (20.38)
Pain: Change at Cycle 11	Number Analyzed	169 participants	153 participants
		-11.65 (19.35)	-8.01 (18.97)
Pain: Change at Cycle 12	Number Analyzed	159 participants	138 participants
		-11.76 (19.87)	-7.19 (19.11)
Pain: Change at Cycle 13	Number Analyzed	141 participants	110 participants
		-11.92 (18.93)	-9.24 (19.79)
Pain: Change at Cycle 14	Number Analyzed	136 participants	101 participants
		-11.66 (19.51)	-9.82 (19.91)
Pain: Change at Cycle 15	Number Analyzed	131 participants	96 participants
		-11.15 (18.16)	-8.51 (20.94)
Pain: Change at Cycle 16	Number Analyzed	116 participants	84 participants
		-8.72 (18.02)	-10.52 (21.30)
Pain: Change at Cycle 17	Number Analyzed	112 participants	73 participants
		-8.88 (18.17)	-9.93 (17.27)
Pain: Change at Cycle 18	Number Analyzed	102 participants	70 participants
		-8.31 (18.33)	-11.19 (18.16)
Pain: Change at Cycle 19	Number Analyzed	96 participants	65 participants
		-6.63 (17.25)	-10.38 (14.51)
Pain: Change at Cycle 20	Number Analyzed	84 participants	62 participants
		-5.72 (19.98)	-10.35 (16.65)
Pain: Change at Cycle 21	Number Analyzed	79 participants	53 participants
		-8.19 (18.27)	-7.55 (16.77)
Pain: Change at Cycle 22	Number Analyzed	67 participants	46 participants
		-9.08 (18.10)	-9.42 (16.72)
Pain: Change at Cycle 23	Number Analyzed	63 participants	43 participants
		-9.66 (20.75)	-8.53 (19.96)
Pain: Change at Cycle 24	Number Analyzed	60 participants	39 participants
		-9.86 (21.56)	-8.76 (15.53)
Pain: Change at Cycle 25	Number Analyzed	52 participants	35 participants
		-10.58 (19.88)	-8.10 (18.69)
Pain: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		-9.01 (17.99)	-9.41 (17.58)
Pain: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		-12.02 (17.28)	-9.23 (14.58)
Pain: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		-11.54 (18.20)	-7.33 (13.46)
Pain: Change at PT Visit 1	Number Analyzed	176 participants	196 participants
		-1.70 (23.07)	-2.99 (23.86)
Pain: Change at PT Visit 2	Number Analyzed	99 participants	106 participants
		-7.49 (24.09)	-0.03 (22.04)
Reflux Symptoms: Cycle 1 (Baseline)	Number Analyzed	367 participants	373 participants
		16.68 (19.03)	17.34 (18.31)
Reflux Symptoms: Change at Cycle 2	Number Analyzed	331 participants	333 participants
		-0.13 (16.33)	-1.99 (18.03)
Reflux Symptoms: Change at Cycle 3	Number Analyzed	318 participants	309 participants
		-0.52 (18.95)	-2.28 (19.53)
Reflux Symptoms: Change at Cycle 4	Number Analyzed	295 participants	289 participants
		-0.98 (19.18)	-1.90 (19.93)
Reflux Symptoms: Change at Cycle 5	Number Analyzed	283 participants	285 participants
		-1.92 (18.98)	-1.72 (20.10)
Reflux Symptoms: Change at Cycle 6	Number Analyzed	270 participants	252 participants
		-2.90 (20.42)	-3.59 (19.04)
Reflux Symptoms: Change at Cycle 7	Number Analyzed	239 participants	226 participants
		-4.18 (18.36)	-3.20 (20.21)
Reflux Symptoms: Change at Cycle 8	Number Analyzed	233 participants	213 participants
		-4.96 (19.39)	-5.74 (19.53)
Reflux Symptoms: Change at Cycle 9	Number Analyzed	207 participants	193 participants
		-5.02 (18.97)	-5.18 (19.81)
Reflux Symptoms: Change at Cycle 10	Number Analyzed	186 participants	163 participants
		-6.12 (17.81)	-6.48 (18.55)
Reflux Symptoms: Change at Cycle 11	Number Analyzed	169 participants	153 participants
		-6.44 (18.74)	-6.03 (18.07)
Reflux Symptoms: Change at Cycle 12	Number Analyzed	158 participants	138 participants
		-4.82 (18.00)	-7.49 (16.99)
Reflux Symptoms: Change at Cycle 13	Number Analyzed	141 participants	110 participants
		-6.42 (17.09)	-6.77 (18.19)
Reflux Symptoms: Change at Cycle 14	Number Analyzed	136 participants	101 participants
		-5.39 (18.24)	-7.37 (17.45)
Reflux Symptoms: Change at Cycle 15	Number Analyzed	131 participants	96 participants
		-5.00 (16.66)	-4.98 (18.72)
Reflux Symptoms: Change at Cycle 16	Number Analyzed	116 participants	84 participants
		-3.07 (18.39)	-4.89 (22.31)
Reflux Symptoms: Change at Cycle 17	Number Analyzed	111 participants	73 participants
		-3.35 (18.38)	-4.57 (20.44)
Reflux Symptoms: Change at Cycle 18	Number Analyzed	102 participants	70 participants
		-2.94 (18.36)	-6.51 (20.33)
Reflux Symptoms: Change at Cycle 19	Number Analyzed	96 participants	65 participants
		-2.43 (16.38)	-6.15 (18.43)
Reflux Symptoms: Change at Cycle 20	Number Analyzed	84 participants	62 participants
		-1.85 (18.32)	-5.38 (18.63)
Reflux Symptoms: Change at Cycle 21	Number Analyzed	79 participants	53 participants
		-1.83 (18.44)	-4.19 (17.73)
Reflux Symptoms: Change at Cycle 22	Number Analyzed	67 participants	46 participants
		-3.81 (19.30)	-7.00 (19.65)
Reflux Symptoms: Change at Cycle 23	Number Analyzed	63 participants	43 participants
		-5.11 (17.03)	-6.98 (19.70)
Reflux Symptoms: Change at Cycle 24	Number Analyzed	60 participants	39 participants
		-4.07 (19.30)	-7.98 (18.19)
Reflux Symptoms: Change at Cycle 25	Number Analyzed	52 participants	35 participants
		-5.56 (18.86)	-5.71 (16.69)
Reflux Symptoms: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		-4.99 (20.67)	-4.30 (21.98)
Reflux Symptoms: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		-7.75 (20.51)	-6.75 (16.10)
Reflux Symptoms: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		-7.12 (18.64)	-4.44 (11.56)
Reflux Symptoms: Change at PT Visit 1	Number Analyzed	176 participants	196 participants
		0.88 (20.01)	-0.45 (22.92)
Reflux Symptoms: Change at PT Visit 2	Number Analyzed	99 participants	106 participants
		0.56 (18.67)	-1.47 (22.28)
Taste: Cycle 1 (Baseline)	Number Analyzed	365 participants	372 participants
		13.79 (23.99)	16.22 (25.49)
Taste: Change at Cycle 2	Number Analyzed	328 participants	333 participants
		12.09 (28.78)	6.61 (26.94)
Taste: Change at Cycle 3	Number Analyzed	317 participants	307 participants
		16.72 (32.11)	9.99 (30.16)
Taste: Change at Cycle 4	Number Analyzed	293 participants	286 participants
		18.43 (34.70)	11.07 (31.93)
Taste: Change at Cycle 5	Number Analyzed	282 participants	284 participants
		17.61 (32.93)	11.85 (30.25)
Taste: Change at Cycle 6	Number Analyzed	269 participants	251 participants
		17.97 (31.20)	11.82 (32.21)
Taste: Change at Cycle 7	Number Analyzed	238 participants	225 participants
		16.25 (33.51)	9.19 (31.09)
Taste: Change at Cycle 8	Number Analyzed	232 participants	213 participants
		11.64 (29.81)	3.29 (28.13)
Taste: Change at Cycle 9	Number Analyzed	206 participants	193 participants
		9.22 (28.25)	1.73 (26.30)
Taste: Change at Cycle 10	Number Analyzed	185 participants	164 participants
		7.93 (26.41)	1.63 (28.79)
Taste: Change at Cycle 11	Number Analyzed	168 participants	153 participants
		4.96 (26.72)	2.61 (26.91)
Taste: Change at Cycle 12	Number Analyzed	158 participants	138 participants
		5.27 (24.82)	0.24 (24.66)
Taste: Change at Cycle 13	Number Analyzed	139 participants	110 participants
		4.08 (25.53)	-0.91 (25.33)
Taste: Change at Cycle 14	Number Analyzed	136 participants	101 participants
		0.49 (25.66)	-5.28 (24.37)
Taste: Change at Cycle 15	Number Analyzed	130 participants	96 participants
		3.08 (24.36)	-1.04 (26.25)
Taste: Change at Cycle 16	Number Analyzed	115 participants	84 participants
		5.51 (27.90)	-3.57 (20.71)
Taste: Change at Cycle 17	Number Analyzed	111 participants	73 participants
		4.80 (24.96)	-3.65 (23.28)
Taste: Change at Cycle 18	Number Analyzed	102 participants	70 participants
		3.59 (23.87)	-4.29 (23.34)
Taste: Change at Cycle 19	Number Analyzed	96 participants	65 participants
		3.13 (25.17)	-4.62 (15.45)
Taste: Change at Cycle 20	Number Analyzed	84 participants	62 participants
		5.56 (27.78)	-3.76 (18.21)
Taste: Change at Cycle 21	Number Analyzed	79 participants	53 participants
		6.33 (27.26)	-5.03 (17.78)
Taste: Change at Cycle 22	Number Analyzed	67 participants	46 participants
		9.45 (30.04)	-4.35 (16.64)
Taste: Change at Cycle 23	Number Analyzed	63 participants	43 participants
		8.99 (30.06)	0.00 (23.00)
Taste: Change at Cycle 24	Number Analyzed	60 participants	39 participants
		7.78 (28.37)	-5.13 (19.55)
Taste: Change at Cycle 25	Number Analyzed	52 participants	35 participants
		3.21 (28.97)	-4.76 (18.33)
Taste: Change at Cycle 26	Number Analyzed	49 participants	31 participants
		4.08 (34.45)	-3.23 (21.70)
Taste: Change at Cycle 27	Number Analyzed	43 participants	28 participants
		4.65 (29.62)	-3.57 (20.96)
Taste: Change at Cycle 28	Number Analyzed	39 participants	25 participants
		3.42 (21.35)	-6.67 (25.46)
Taste: Change at PT Visit 1	Number Analyzed	175 participants	195 participants
		12.76 (34.59)	9.06 (33.56)
Taste: Change at PT Visit 2	Number Analyzed	99 participants	105 participants
		8.42 (31.35)	6.67 (28.64)

11. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Pertuzumab
Description	[Not Specified]
Time Frame	Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis included all participants who were treated with study medication and who had at least one measurable concentration of pertuzumab or trastuzumab. In this analysis, results are reported only for evaluable participants who received pertuzumab.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed		374
Mean (Standard Deviation); Unit of Measure: micrograms per milliliter (μg/mL)
Cycle 1	Number Analyzed	374 participants
		258 (90.3)
Cycle 2	Number Analyzed	346 participants
		288 (83.7)
Cycle 4	Number Analyzed	302 participants
		341 (111)
Cycle 8	Number Analyzed	106 participants
		371 (127)

12. Secondary Outcome

Title	Cmax of Trastuzumab
Description	[Not Specified]
Time Frame	Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis included all participants who were treated with study medication and who had at least one measurable concentration of pertuzumab or trastuzumab. Data are reported for evaluable participants.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed		372	375
Mean (Standard Deviation); Unit of Measure: μg/mL
Cycle 1	Number Analyzed	372 participants	375 participants
		142 (86.8)	139 (58.6)
Cycle 2	Number Analyzed	346 participants	354 participants
		120 (46.6)	120 (44.3)
Cycle 4	Number Analyzed	304 participants	299 participants
		127 (50.9)	129 (58.1)
Cycle 8	Number Analyzed	115 participants	90 participants
		130 (50.8)	147 (90.2)

13. Secondary Outcome

Title	Minimum Serum Concentration (Cmin) of Pertuzumab
Description	[Not Specified]
Time Frame	Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis included all participants who were treated with study medication and who had at least one measurable concentration of pertuzumab or trastuzumab. In this analysis, results are reported only for evaluable participants who received pertuzumab.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed		376
Mean (Standard Deviation); Unit of Measure: μg/mL
Cycle 1	Number Analyzed	376 participants
		NA [1] (NA)
Cycle 2	Number Analyzed	349 participants
		42.4 (24.8)
Cycle 3	Number Analyzed	327 participants
		74.0 (40.9)
Cycle 4	Number Analyzed	305 participants
		90.4 (42.4)
Cycle 6	Number Analyzed	274 participants
		114 (51.8)
Cycle 8	Number Analyzed	114 participants
		142 (67.9)

[1]

The Cmin of pertuzumab at Cycle 1 (before first dose) is non-reportable (i.e., lower than quantifiable).

14. Secondary Outcome

Title	Cmin of Trastuzumab
Description	[Not Specified]
Time Frame	Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis included all participants who were treated with study medication and who had at least one measurable concentration of pertuzumab or trastuzumab. Data are reported for evaluable participants.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.	Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Overall Number of Participants Analyzed		379	381
Mean (Standard Deviation); Unit of Measure: μg/mL
Cycle 1	Number Analyzed	379 participants	381 participants
		NA [1] (NA)	NA [1] (NA)
Cycle 2	Number Analyzed	345 participants	354 participants
		15.4 (11.3)	17.2 (15.4)
Cycle 3	Number Analyzed	328 participants	326 participants
		19.9 (13.4)	20.7 (15.2)
Cycle 4	Number Analyzed	305 participants	300 participants
		22.9 (12.7)	24.1 (19.0)
Cycle 6	Number Analyzed	274 participants	254 participants
		26.3 (14.8)	29.8 (21.9)
Cycle 8	Number Analyzed	114 participants	92 participants
		32.7 (15.0)	37.4 (20.3)

[1]

The Cmin of trastuzumab at Cycle 1 (before first dose) is non-reportable (i.e., lower than quantifiable).

Adverse Events

Time Frame	From Baseline until end of post-treatment follow-up (up to 70 months)
Adverse Event Reporting Description	All adverse events (AEs) that occurred during the study and until the post-treatment safety follow-up visit approximately 28 days after last study medication were to be recorded. The safety population included all participants who received any amount of any study medication: those who received any amount of pertuzumab were included in the pertuzumab arm; all other treated participants were included in the placebo arm.
Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy		Placebo + Trastuzumab + Chemotherapy
Arm/Group Description	Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.		Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
All-Cause Mortality
	Pertuzumab + Trastuzumab + Chemotherapy		Placebo + Trastuzumab + Chemotherapy
	Affected / at Risk (%)		Affected / at Risk (%)
Total	299/385 (77.66%)		318/388 (81.96%)
Serious Adverse Events
	Pertuzumab + Trastuzumab + Chemotherapy		Placebo + Trastuzumab + Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	178/385 (46.23%)		156/388 (40.21%)
Blood and lymphatic system disorders
Anaemia † 1	8/385 (2.08%)	11	16/388 (4.12%)	19
Disseminated intravascular coagulation † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Febrile neutropenia † 1	6/385 (1.56%)	6	9/388 (2.32%)	9
Neutropenia † 1	3/385 (0.78%)	4	3/388 (0.77%)	3
Pancytopenia † 1	0/385 (0.00%)	0	3/388 (0.77%)	3
Thrombocytopenia † 1	2/385 (0.52%)	2	1/388 (0.26%)	1
Cardiac disorders
Acute myocardial infarction † 1	4/385 (1.04%)	4	0/388 (0.00%)	0
Atrial fibrillation † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Atrial septal defect acquired † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Atrioventricular block complete † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Cardiac arrest † 1	1/385 (0.26%)	1	1/388 (0.26%)	1
Cardiac failure † 1	3/385 (0.78%)	3	1/388 (0.26%)	1
Cardiac ventricular thrombosis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Intracardiac thrombus † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Myocardial infarction † 1	2/385 (0.52%)	2	1/388 (0.26%)	1
Myocarditis † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Prinzmetal angina † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Acute coronary syndrome † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Ear and labyrinth disorders
Tinnitus † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Endocrine disorders
Autoimmune thyroiditis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Inappropriate antidiuretic hormone secretion † 1	1/385 (0.26%)	1	1/388 (0.26%)	1
Pseudoaldosteronism † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	3/385 (0.78%)	3	2/388 (0.52%)	2
Abdominal pain upper † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Colitis † 1	0/385 (0.00%)	0	2/388 (0.52%)	2
Constipation † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Diarrhoea † 1	17/385 (4.42%)	20	20/388 (5.15%)	22
Duodenal stenosis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Dysphagia † 1	4/385 (1.04%)	4	1/388 (0.26%)	1
Enteritis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Enterocolitis † 1	0/385 (0.00%)	0	4/388 (1.03%)	4
Gastric haemorrhage † 1	6/385 (1.56%)	7	2/388 (0.52%)	2
Gastric perforation † 1	2/385 (0.52%)	2	2/388 (0.52%)	2
Gastric stenosis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Gastric ulcer † 1	1/385 (0.26%)	1	1/388 (0.26%)	1
Gastrointestinal disorder † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Gastrointestinal haemorrhage † 1	0/385 (0.00%)	0	3/388 (0.77%)	4
Gastrointestinal inflammation † 1	1/385 (0.26%)	1	1/388 (0.26%)	1
Gastrointestinal obstruction † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Gastrointestinal perforation † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Gastrointestinal ulcer † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Gastrooesophageal reflux disease † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Haematemesis † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Haemorrhoids † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Ileus † 1	2/385 (0.52%)	2	1/388 (0.26%)	2
Ileus paralytic † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Intestinal mass † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Intestinal obstruction † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Lower gastrointestinal haemorrhage † 1	0/385 (0.00%)	0	2/388 (0.52%)	2
Melaena † 1	2/385 (0.52%)	2	0/388 (0.00%)	0
Nausea † 1	7/385 (1.82%)	7	7/388 (1.80%)	9
Obstruction gastric † 1	2/385 (0.52%)	2	5/388 (1.29%)	7
Oesophageal haemorrhage † 1	1/385 (0.26%)	1	1/388 (0.26%)	1
Stomatitis † 1	2/385 (0.52%)	2	2/388 (0.52%)	2
Upper gastrointestinal haemorrhage † 1	3/385 (0.78%)	3	5/388 (1.29%)	5
Vomiting † 1	7/385 (1.82%)	8	13/388 (3.35%)	17
Gastric pneumatosis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Mechanical ileus † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
General disorders
Asthenia † 1	5/385 (1.30%)	8	1/388 (0.26%)	1
Chest pain † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Death † 1	8/385 (2.08%)	8	9/388 (2.32%)	9
Fatigue † 1	4/385 (1.04%)	4	0/388 (0.00%)	0
General physical health deterioration † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Hypothermia † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Malaise † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Mucosal inflammation † 1	4/385 (1.04%)	4	3/388 (0.77%)	3
Multiple organ dysfunction syndrome † 1	0/385 (0.00%)	0	2/388 (0.52%)	2
Non-cardiac chest pain † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Pyrexia † 1	2/385 (0.52%)	2	1/388 (0.26%)	1
Hepatobiliary disorders
Cholecystitis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Cholecystitis acute † 1	1/385 (0.26%)	1	3/388 (0.77%)	4
Hepatic function abnormal † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Immune system disorders
Cytokine release syndrome † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Hypersensitivity † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Infections and infestations
Abdominal infection † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Arthritis bacterial † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Bacteraemia † 1	2/385 (0.52%)	2	1/388 (0.26%)	1
Biliary sepsis † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Bronchitis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Cellulitis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Device related infection † 1	2/385 (0.52%)	2	0/388 (0.00%)	0
Device related sepsis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Diarrhoea infectious † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Gastroenteritis † 1	0/385 (0.00%)	0	2/388 (0.52%)	2
Hepatitis B † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Infection † 1	0/385 (0.00%)	0	3/388 (0.77%)	3
Liver abscess † 1	1/385 (0.26%)	1	2/388 (0.52%)	2
Parotitis † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Peritonitis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Pneumonia † 1	14/385 (3.64%)	15	14/388 (3.61%)	14
Pneumonia Klebsiella † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Respiratory tract infection † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Sepsis † 1	8/385 (2.08%)	8	2/388 (0.52%)	2
Septic shock † 1	3/385 (0.78%)	3	4/388 (1.03%)	4
Upper respiratory tract infection † 1	3/385 (0.78%)	3	2/388 (0.52%)	2
Urinary tract infection † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Urosepsis † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Appendicitis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Vascular device infection † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Injury, poisoning and procedural complications
Anastomotic stenosis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Craniocerebral injury † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Fall † 1	2/385 (0.52%)	2	1/388 (0.26%)	1
Femoral neck fracture † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Fracture † 1	2/385 (0.52%)	2	0/388 (0.00%)	0
Gastrointestinal anastomotic leak † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Head injury † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Hip fracture † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Infusion related reaction † 1	3/385 (0.78%)	3	2/388 (0.52%)	2
Injury † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Limb injury † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Spinal compression fracture † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Ankle fracture † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Thermal burn † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Aspartate aminotransferase increased † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Blood bilirubin increased † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Blood creatine phosphokinase increased † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Blood creatinine increased † 1	1/385 (0.26%)	1	2/388 (0.52%)	2
Creatinine renal clearance decreased † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Weight decreased † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Biopsy bone marrow † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Metabolism and nutrition disorders
Cachexia † 1	1/385 (0.26%)	2	0/388 (0.00%)	0
Decreased appetite † 1	17/385 (4.42%)	18	9/388 (2.32%)	9
Dehydration † 1	9/385 (2.34%)	10	9/388 (2.32%)	9
Diabetes mellitus † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Diabetes mellitus inadequate control † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Failure to thrive † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Hyperglycaemia † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Hypernatraemia † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Hypocalcaemia † 1	2/385 (0.52%)	2	1/388 (0.26%)	1
Hypokalaemia † 1	7/385 (1.82%)	8	1/388 (0.26%)	1
Hypomagnesaemia † 1	2/385 (0.52%)	2	2/388 (0.52%)	2
Hyponatraemia † 1	2/385 (0.52%)	2	2/388 (0.52%)	2
Malnutrition † 1	1/385 (0.26%)	1	1/388 (0.26%)	2
Musculoskeletal and connective tissue disorders
Back pain † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Gouty arthritis † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Muscular weakness † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome † 1	1/385 (0.26%)	1	1/388 (0.26%)	1
Rectosigmoid cancer stage 0 † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Second primary malignancy † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Tumour haemorrhage † 1	4/385 (1.04%)	4	1/388 (0.26%)	1
Plasma cell myeloma † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Nervous system disorders
Anticholinergic syndrome † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Cerebral haemorrhage † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Cerebral infarction † 1	0/385 (0.00%)	0	2/388 (0.52%)	2
Cerebral ischaemia † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Cerebrovascular accident † 1	0/385 (0.00%)	0	3/388 (0.77%)	3
Dizziness † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Hydrocephalus † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Ischaemic cerebral infarction † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Ischaemic stroke † 1	1/385 (0.26%)	1	1/388 (0.26%)	1
Loss of consciousness † 1	1/385 (0.26%)	2	0/388 (0.00%)	0
Neuropathy peripheral † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Presyncope † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Seizure † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Syncope † 1	2/385 (0.52%)	2	0/388 (0.00%)	0
Subarachnoid haemorrhage † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Epilepsy † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Product Issues
Device dislocation † 1	0/385 (0.00%)	0	2/388 (0.52%)	2
Device occlusion † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Psychiatric disorders
Delirium † 1	1/385 (0.26%)	2	0/388 (0.00%)	0
Depression † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Suicide attempt † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Renal and urinary disorders
Acute kidney injury † 1	7/385 (1.82%)	7	4/388 (1.03%)	4
Hydronephrosis † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Renal failure † 1	2/385 (0.52%)	2	3/388 (0.77%)	3
Renal impairment † 1	1/385 (0.26%)	1	2/388 (0.52%)	2
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	0/385 (0.00%)	0	2/388 (0.52%)	2
Bronchospasm † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Dyspnoea † 1	2/385 (0.52%)	2	1/388 (0.26%)	1
Epistaxis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Hypoxia † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Pneumothorax † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Pulmonary embolism † 1	6/385 (1.56%)	6	2/388 (0.52%)	2
Respiratory failure † 1	0/385 (0.00%)	0	2/388 (0.52%)	2
Skin and subcutaneous tissue disorders
Actinic keratosis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Vascular disorders
Aortic aneurysm † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Deep vein thrombosis † 1	3/385 (0.78%)	3	0/388 (0.00%)	0
Embolism † 1	2/385 (0.52%)	2	1/388 (0.26%)	1
Haemodynamic instability † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Hypertensive crisis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Hypotension † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Hypovolaemic shock † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Iliac artery occlusion † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Orthostatic hypotension † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Peripheral ischaemia † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Subclavian vein thrombosis † 1	0/385 (0.00%)	0	1/388 (0.26%)	1
Thrombosis † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Varicose vein † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
Venous thrombosis limb † 1	1/385 (0.26%)	1	0/388 (0.00%)	0
1 Term from vocabulary, MedDRA, Version 22.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pertuzumab + Trastuzumab + Chemotherapy		Placebo + Trastuzumab + Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	373/385 (96.88%)		376/388 (96.91%)
Blood and lymphatic system disorders
Anaemia † 1	159/385 (41.30%)	208	142/388 (36.60%)	189
Leukopenia † 1	80/385 (20.78%)	148	69/388 (17.78%)	113
Neutropenia † 1	200/385 (51.95%)	340	202/388 (52.06%)	298
Thrombocytopenia † 1	61/385 (15.84%)	105	73/388 (18.81%)	100
Gastrointestinal disorders
Abdominal distension † 1	25/385 (6.49%)	36	19/388 (4.90%)	24
Abdominal pain † 1	44/385 (11.43%)	60	51/388 (13.14%)	59
Abdominal pain upper † 1	28/385 (7.27%)	33	23/388 (5.93%)	25
Constipation † 1	56/385 (14.55%)	64	84/388 (21.65%)	107
Diarrhoea † 1	230/385 (59.74%)	351	125/388 (32.22%)	173
Dyspepsia † 1	24/385 (6.23%)	27	30/388 (7.73%)	40
Dysphagia † 1	28/385 (7.27%)	34	32/388 (8.25%)	38
Nausea † 1	224/385 (58.18%)	314	218/388 (56.19%)	311
Stomatitis † 1	81/385 (21.04%)	102	69/388 (17.78%)	86
Vomiting † 1	147/385 (38.18%)	200	122/388 (31.44%)	167
General disorders
Asthenia † 1	59/385 (15.32%)	83	60/388 (15.46%)	78
Chills † 1	37/385 (9.61%)	37	17/388 (4.38%)	19
Fatigue † 1	144/385 (37.40%)	182	123/388 (31.70%)	166
Mucosal inflammation † 1	43/385 (11.17%)	60	34/388 (8.76%)	40
Oedema † 1	20/385 (5.19%)	33	19/388 (4.90%)	32
Oedema peripheral † 1	27/385 (7.01%)	31	33/388 (8.51%)	36
Pyrexia † 1	55/385 (14.29%)	81	60/388 (15.46%)	69
Infections and infestations
Upper respiratory tract infection † 1	24/385 (6.23%)	37	13/388 (3.35%)	18
Nasopharyngitis † 1	21/385 (5.45%)	22	18/388 (4.64%)	24
Injury, poisoning and procedural complications
Infusion related reaction † 1	46/385 (11.95%)	52	23/388 (5.93%)	26
Investigations
Blood creatinine increased † 1	29/385 (7.53%)	36	22/388 (5.67%)	31
Creatinine renal clearance decreased † 1	71/385 (18.44%)	97	50/388 (12.89%)	65
Weight decreased † 1	78/385 (20.26%)	80	49/388 (12.63%)	51
Ejection fraction decreased † 1	20/385 (5.19%)	24	18/388 (4.64%)	20
Metabolism and nutrition disorders
Decreased appetite † 1	172/385 (44.68%)	243	158/388 (40.72%)	218
Hypoalbuminaemia † 1	20/385 (5.19%)	24	21/388 (5.41%)	23
Hypocalcaemia † 1	24/385 (6.23%)	32	23/388 (5.93%)	26
Hypokalaemia † 1	74/385 (19.22%)	98	46/388 (11.86%)	57
Hypomagnesaemia † 1	30/385 (7.79%)	38	21/388 (5.41%)	22
Hyponatraemia † 1	17/385 (4.42%)	19	29/388 (7.47%)	29
Nervous system disorders
Dizziness † 1	31/385 (8.05%)	35	30/388 (7.73%)	38
Dysgeusia † 1	31/385 (8.05%)	40	27/388 (6.96%)	27
Neuropathy peripheral † 1	34/385 (8.83%)	38	29/388 (7.47%)	30
Peripheral sensory neuropathy † 1	29/385 (7.53%)	37	34/388 (8.76%)	35
Psychiatric disorders
Insomnia † 1	34/385 (8.83%)	45	46/388 (11.86%)	48
Respiratory, thoracic and mediastinal disorders
Cough † 1	25/385 (6.49%)	30	21/388 (5.41%)	32
Dyspnoea † 1	22/385 (5.71%)	25	14/388 (3.61%)	18
Hiccups † 1	33/385 (8.57%)	37	37/388 (9.54%)	45
Skin and subcutaneous tissue disorders
Alopecia † 1	21/385 (5.45%)	25	25/388 (6.44%)	26
Dry skin † 1	32/385 (8.31%)	39	18/388 (4.64%)	21
Palmar-plantar erythrodysaesthesia syndrome † 1	86/385 (22.34%)	91	100/388 (25.77%)	112
Pruritus † 1	38/385 (9.87%)	51	16/388 (4.12%)	25
Rash † 1	27/385 (7.01%)	30	13/388 (3.35%)	15
Skin hyperpigmentation † 1	17/385 (4.42%)	17	21/388 (5.41%)	21
Vascular disorders
Hypertension † 1	20/385 (5.19%)	24	21/388 (5.41%)	21
1 Term from vocabulary, MedDRA, Version 22.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but only after the first publication or presentation that involves the overall study. The Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Siddiqui A, Heeson S, Kiermaier A, Macharia H, Restuccia E, Kang YK. Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial. Gastric Cancer. 2023 Jan;26(1):123-131. doi: 10.1007/s10120-022-01335-4. Epub 2022 Sep 6.

Liu T, Qin Y, Li J, Xu R, Xu J, Yang S, Qin S, Bai Y, Wu C, Mao Y, Wu H, Ge Y, Shen L. Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial. Cancer Commun (Lond). 2019 Jun 24;39(1):38. doi: 10.1186/s40880-019-0384-6.

Kirschbrown WP, Wang B, Nijem I, Ohtsu A, Hoff PM, Shah MA, Shen L, Kang YK, Alsina M, Girish S, Garg A. Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer. Cancer Chemother Pharmacol. 2019 Sep;84(3):539-550. doi: 10.1007/s00280-019-03871-w. Epub 2019 Jun 10.

Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. doi: 10.1016/S1470-2045(18)30481-9. Epub 2018 Sep 11.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01774786
• Other Study ID Numbers: BO25114; 2012-003554-83 ( EudraCT Number )
• First Submitted: January 21, 2013
• First Posted: January 24, 2013
• Results First Submitted: December 8, 2017
• Results First Posted: February 14, 2018
• Last Update Posted: December 30, 2020