Study of TAS-102 or Placebo Plus BSC in Patients With Metastatic Gastric Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02500043

Recruitment Status : Completed

First Posted : July 16, 2015

Results First Posted : September 16, 2021

Last Update Posted : September 16, 2021

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Taiho Oncology, Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Refractory Metastatic Gastric Cancer
Interventions	Drug: TAS-102 Drug: Placebo
Enrollment	507

Participant Flow

Recruitment Details	The study was conducted at study centers in 17 countries. Participants were involved in the study from 24 February 2016 to 19 December 2019.
Pre-assignment Details	Overall, 625 participants were screened, of which 118 were screen failures due to inclusion/exclusion criteria not met and 507 were randomized and treated with TAS-102 or placebo along with Best supportive care (BSC) (BSC was given to prevent, control, or relieve complications and side effects with the intention to maximize quality of life (QoL) without a specific antineoplastic regimen).


Arm/Group Title	TAS-102+BSC	Placebo+BSC
Arm/Group Description	Participants received 35 milligrams...	Participants received 35 mg/m^2 of ...
Arm/Group Description	Participants received 35 milligrams per meter square (mg/m^2) of TAS-102 tablets orally twice daily (BID) for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Period Title: Overall Study
Started	337	170
As-Treated (AT) Population ^[1]	335	168
Completed	0	0
Not Completed	337	170
Reason Not Completed
Randomized, but not Treated	2	2
Ongoing at Date of Cut-Off	19	3
Adverse Event	33	11
Clinical Progression	54	35
Radiological Progression	192	110
Physician's Decision	11	3
Withdrawal by Subject	14	4
Death	11	2
Protocol Deviation	1	0
[1] All participants who received at least 1 dose of study treatment.

Baseline Characteristics

Arm/Group Title		TAS-102+BSC	Placebo+BSC	Total
Arm/Group Description		Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...	Total of all reporting groups
Arm/Group Description		Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Total of all reporting groups
Overall Number of Baseline Participants		337	170	507
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Analysis was performed on the Intent-to-Treat (ITT) population that included all randomized participants, regardless of whether or not study treatment was administered.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	337 participants	170 participants	507 participants
		62.8 (10.78)	62.0 (10.04)	62.5 (10.53)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	337 participants	170 participants	507 participants
	Female	85 25.2%	53 31.2%	138 27.2%
	Male	252 74.8%	117 68.8%	369 72.8%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	337 participants	170 participants	507 participants
White		244 72.4%	113 66.5%	357 70.4%
Black/African American		1 0.3%	2 1.2%	3 0.6%
Asian		51 15.1%	29 17.1%	80 15.8%
Not collectable		38 11.3%	24 14.1%	62 12.2%
Other		3 0.9%	2 1.2%	5 1.0%
European Cooperative Oncology Group (ECOG) Performance Status ^[1] Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	337 participants	170 participants	507 participants
ECOG Grade 0		123 36.5%	68 40.0%	191 37.7%
ECOG Grade 1		214 63.5%	102 60.0%	316 62.3%
		[1] Measure Description: The ECOG performance status was used to evaluate participant's disease progression and the effect of the disease on the participant's activities of daily living. It ranged on the scale from 0-5 (0 equal to [=] normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead). Time to definitive deterioration in ECOG performance status score from baseline was defined as change from 0, 1 to greater than or equal to (>=2), or from 2 to >=3.

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	OS was defined as the time from the date of randomization to the date ...
Description	OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death were censored at last follow-up or cut-off date, whichever comes first. OS was estimated by Kaplan-Meier method.
Time Frame	From the date of randomization to the data cut-off date (maximum duration: up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered.


Arm/Group Title	TAS-102+BSC	Placebo+BSC
Arm/Group Description:	Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...
Arm/Group Description:	Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Overall Number of Participants Analyzed	337	170
Median (95% Confidence Interval) Unit of Measure: months
	5.7 (4.8 to 6.2)	3.6 (3.1 to 4.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS-102+BSC, Placebo+BSC
	Comments	TAS-102+BSC and Placebo+BSC were compared using the stratified log-rank test using the 3 randomization stratification factors (region, ECOG performance status, and prior treatment with ramucirumab). The hazard ratio was estimated using a stratified Cox's proportional hazard (CPH) model and survival was summarized using Kaplan Meier estimates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0003
	Comments	One-sided P-Value.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.6917
	Confidence Interval	(2-Sided) 95% 0.5597 to 0.8548
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time from randomization until the date of first...
Description	PFS was defined as the time from randomization until the date of first occurrence of investigator-assessed radiological disease progression or death due to any cause, whichever came first. Disease progression as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) for target lesions were defined as target lesions with at least 20 % relative increase in the sum of diameters with reference to the smallest sum on study, including the baseline sum and this sum demonstrated an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions or Unequivocal progression of existing non-target lesions. All alive participants with no disease progression as of the analysis cut-off date were censored at the last tumor assessment. PFS was estimated by Kaplan-Meier method.
Time Frame	From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered.


Arm/Group Title	TAS-102+BSC	Placebo+BSC
Arm/Group Description:	Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...
Arm/Group Description:	Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Overall Number of Participants Analyzed	337	170
Median (95% Confidence Interval) Unit of Measure: months
	2.0 (1.9 to 2.3)	1.8 (1.7 to 1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS-102+BSC, Placebo+BSC
	Comments	TAS-102+BSC and Placebo+BSC were compared using the stratified log-rank test using the 3 randomization stratification factors (region, ECOG performance status, and prior treatment with ramucirumab). The hazard ratio was estimated using a stratified CPH model and survival was summarized using Kaplan Meier estimates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.5723
	Confidence Interval	(2-Sided) 95% 0.4674 to 0.7008
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE)
Description	Any untoward medical condition that occurs in a participants while par...
Description	Any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study medication was considered an adverse event (AE). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs/TESAEs were defined as events that started on or after treatment or started before treatment and worsened after the start of treatment through 30 days after the last dose of study treatment.
Time Frame	From the first dose of study treatment until 30 days after the last dose of study treatment (maximum duration: up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the As-treated (AT) population that included all participants who received at least 1 dose of study treatment.


Arm/Group Title	TAS-102+BSC	Placebo+BSC
Arm/Group Description:	Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...
Arm/Group Description:	Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Overall Number of Participants Analyzed	335	168
Measure Type: Count of Participants Unit of Measure: Participants
TEAE	319 95.2%	151 89.9%
TESAE	143 42.7%	70 41.7%

4.Other Pre-specified Outcome


Title	Overall Response Rate (ORR)
Description	Overall response rate was defined as the percentage of participants wi...
Description	Overall response rate was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to < 10 mm. PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference.
Time Frame	From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on tumor response (TR) population that included participants in the ITT population that met 2 criteria: had measurable disease (at least 1 target lesion) at baseline; had at least 1 post-baseline evaluation or early disease progression/cancer-related death occurred before first evaluation on treatment (post-baseline).


Arm/Group Title	TAS-102+BSC	Placebo+BSC
Arm/Group Description:	Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...
Arm/Group Description:	Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Overall Number of Participants Analyzed	290	145
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	4.5 (2.4 to 7.5)	2.1 (0.4 to 5.9)

5.Other Pre-specified Outcome


Title	Disease Control Rate (DCR)
Description	DCR was defined as the proportion of participants with a best overall ...
Description	DCR was defined as the proportion of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD). The assessment of DCR was based on Investigator review of radiologic images and following RECIST criteria (version 1.1, 2009).
Time Frame	From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on TR population that included participants in the ITT population that met 2 criteria: had measurable disease (at least 1 target lesion) at baseline; had at least 1 post-baseline evaluation or early disease progression/cancer-related death occurred before first evaluation on treatment (post-baseline).


Arm/Group Title	TAS-102+BSC	Placebo+BSC
Arm/Group Description:	Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...
Arm/Group Description:	Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Overall Number of Participants Analyzed	290	145
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	44.1 (38.3 to 50.1)	14.5 (9.2 to 21.3)

6.Other Pre-specified Outcome


Title	Time to Deterioration of European Cooperative Oncology Group (ECOG) Performance Status Score From Baseline
Description	The ECOG performance status was used to evaluate participant's disease...
Description	The ECOG performance status was used to evaluate participant's disease progression and the effect of the disease on the participant's activities of daily living. It ranges on the scale from 0-5 (0 = normal activity; 1= symptoms but ambulatory; 2= in bed for < 50% of the time; 3= in bed for > 50% of the time; 4= 100% bedridden; 5= dead). Time to definitive deterioration in ECOG performance status score from baseline was defined as a change from 0, 1 to >=2, or from 2 to >=3.
Time Frame	At the time of randomization (Day 1 Cycle 1) and within 24 hours prior to start of study treatment in every cycle (maximum duration: up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered.


Arm/Group Title	TAS-102+BSC	Placebo+BSC
Arm/Group Description:	Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...
Arm/Group Description:	Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Overall Number of Participants Analyzed	337	170
Median (95% Confidence Interval) Unit of Measure: months
	4.3 (3.7 to 4.7)	2.3 (2.0 to 2.8)

7.Other Pre-specified Outcome


Title	Change From Baseline in Quality of Life European Organization for Research and Treatment for Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30 Score): Global Health Status
Description	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for ev...
Description	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) and other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health and QoL, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 and 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best QoL for participant.
Time Frame	Baseline, Day 1 Cycle 2 up to end of treatment (EOT) (within 30 days of last study treatment) and 30-Day safety follow-up visit (maximum duration: up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered. Here, 'number analyzed' = participants with available data for each specified category.


Arm/Group Title		TAS-102+BSC	Placebo+BSC
Arm/Group Description:		Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...
Arm/Group Description:		Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Overall Number of Participants Analyzed		337	170
Mean (Standard Deviation) Unit of Measure: units on a scale
Cycle 1	Number Analyzed	279 participants	127 participants
Cycle 1		-2.7 (17.56)	-5.9 (22.20)
Cycle 2	Number Analyzed	187 participants	58 participants
Cycle 2		-5.9 (20.51)	-7.3 (25.80)
Cycle 3	Number Analyzed	121 participants	23 participants
Cycle 3		-4.1 (18.26)	-1.4 (22.00)
Cycle 4	Number Analyzed	79 participants	15 participants
Cycle 4		-3.6 (17.54)	-1.7 (22.32)
Cycle 5	Number Analyzed	55 participants	9 participants
Cycle 5		-5.9 (18.05)	11.1 (18.16)
Cycle 6	Number Analyzed	36 participants	8 participants
Cycle 6		-8.8 (23.05)	15.6 (21.10)
Cycle 7	Number Analyzed	28 participants	5 participants
Cycle 7		-9.5 (21.96)	20.0 (4.56)
Cycle 8	Number Analyzed	23 participants	5 participants
Cycle 8		-4.3 (23.82)	16.7 (11.79)
Cycle 9	Number Analyzed	14 participants	3 participants
Cycle 9		2.4 (17.12)	16.7 (16.67)
Cycle 10	Number Analyzed	11 participants	2 participants
Cycle 10		-14.4 (25.57)	25.0 (11.79)
Cycle 11	Number Analyzed	5 participants	2 participants
Cycle 11		-16.7 (37.27)	25.0 (11.79)
Cycle 12	Number Analyzed	2 participants	1 participants
Cycle 12		-8.3 (11.79)	33.3
Cycle 13	Number Analyzed	1 participants	1 participants
Cycle 13		0.0	33.3
Cycle 14	Number Analyzed	0 participants	1 participants
Cycle 14			33.3
Cycle 15	Number Analyzed	0 participants	1 participants
Cycle 15			33.3
Last Collection Cycle	Number Analyzed	283 participants	128 participants
Last Collection Cycle		-8.8 (20.91)	-9.8 (25.34)
Safety Follow-Up	Number Analyzed	39 participants	14 participants
Safety Follow-Up		-16.5 (23.45)	-8.9 (18.33)

8.Other Pre-specified Outcome


Title	EORTC Quality of Life Questionnaire - Gastric-specific Module (EORTC QLQ-STO22): Percentage of Participants With Overall Compliance
Description	The Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22)...
Description	The Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) assessed symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, dietary restrictions, pain QS22, reflux, and anxiety) and 4 single items (dry mouth, hair loss, taste problems, body image). Most questions use 4-point scale (1='Not at all', 2=a little, 3=quite a bit and 4='Very much'). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100, where higher score=better level of functioning or greater degree of symptoms.
Time Frame	Baseline, Cycle 1 Day 1 up to end of treatment (EOT) (within 30 days of last study treatment) (maximum duration: up to approximately 46 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered.


Arm/Group Title	TAS-102+BSC	Placebo+BSC
Arm/Group Description:	Participants received 35 mg/m^2 of ...	Participants received 35 mg/m^2 of ...
Arm/Group Description:	Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.	Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
Overall Number of Participants Analyzed	337	170
Measure Type: Number Unit of Measure: percentage of participants
Dysphagia	86.6	78.2
Dietary Restrictions	86.6	78.2
Pain QS22	86.6	78.2
Reflux	86.6	78.2
Anxiety	86.6	78.2
Dry Mouth	86.4	78.2
Body Image	85.8	78.2
Hair Loss	86.6	78.2
Taste Problems	86.6	78.2

Adverse Events

Time Frame	From first dose of study treatment up to 30 days of last study treatment (maximum duration: up to approximately 46 months).
Adverse Event Reporting Description	Analysis was performed on the AT population.

Arm/Group Title	TAS-102+BSC		Placebo+BSC
Arm/Group Description	Participants received 35 mg/m^2 of ...		Participants received 35 mg/m^2 of ...
Arm/Group Description	Participants received 35 mg/m^2 of TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.		Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met.
All-Cause Mortality
	TAS-102+BSC		Placebo+BSC
	Affected / at Risk (%)		Affected / at Risk (%)
Total	252/335 (75.22%)		141/168 (83.93%)
Serious Adverse Events Serious Adverse Events
	TAS-102+BSC		Placebo+BSC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	143/335 (42.69%)		70/168 (41.67%)
Blood and lymphatic system disorders
Anaemia ^† 1	13/335 (3.88%)	13	4/168 (2.38%)	5
Disseminated intravascular coagulation ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Febrile neutropenia ^† 1	4/335 (1.19%)	4	0/168 (0.00%)	0
Neutropenia ^† 1	4/335 (1.19%)	5	0/168 (0.00%)	0
Pancytopenia ^† 1	7/335 (2.09%)	7	0/168 (0.00%)	0
Thrombocytopenia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cardiac disorders
Acute coronary syndrome ^† 1	2/335 (0.60%)	2	1/168 (0.60%)	1
Atrial fibrillation ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cardio-Respiratory arrest ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Myocardial infarction ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Ear and labyrinth disorders
Vertigo ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Gastrointestinal disorders
Abdominal distension ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Abdominal pain ^† 1	8/335 (2.39%)	8	6/168 (3.57%)	6
Abdominal pain lower ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Abdominal pain upper ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Ascites ^† 1	3/335 (0.90%)	4	7/168 (4.17%)	7
Constipation ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Diarrhoea ^† 1	6/335 (1.79%)	6	0/168 (0.00%)	0
Dysphagia ^† 1	6/335 (1.79%)	6	2/168 (1.19%)	2
Gastric haemorrhage ^† 1	3/335 (0.90%)	3	3/168 (1.79%)	3
Gastric stenosis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Gastric ulcer haemorrhage ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Gastrointestinal haemorrhage ^† 1	4/335 (1.19%)	6	1/168 (0.60%)	1
Gastrointestinal obstruction ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	2
Haematemesis ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Ileus ^† 1	2/335 (0.60%)	3	1/168 (0.60%)	1
Intestinal obstruction ^† 1	4/335 (1.19%)	4	3/168 (1.79%)	4
Large intestinal obstruction ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Lower gastrointestinal haemorrhage ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Melaena ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Nausea ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Obstruction gastric ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Oesophageal obstruction ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Oesophageal pain ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Oesophagitis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Pancreatitis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Small intestinal obstruction ^† 1	3/335 (0.90%)	3	2/168 (1.19%)	2
Stomatitis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Subileus ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Ulcerative gastritis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Upper gastrointestinal haemorrhage ^† 1	2/335 (0.60%)	2	2/168 (1.19%)	2
Vomiting ^† 1	9/335 (2.69%)	9	1/168 (0.60%)	2
General disorders
Asthenia ^† 1	1/335 (0.30%)	1	3/168 (1.79%)	3
Disease progression ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Fatigue ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
General physical health deterioration ^† 1	21/335 (6.27%)	25	15/168 (8.93%)	20
Malaise ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Performance status decreased ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Pyrexia ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Hepatobiliary disorders
Cholangitis ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Cholestasis ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Hepatic failure ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Hepatitis toxic ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	2
Jaundice ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Jaundice cholestatic ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Infections and infestations
Biliary sepsis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Cellulitis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Clostridium difficile colitis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Clostridium difficile infection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Escherichia sepsis ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Infection ^† 1	2/335 (0.60%)	3	1/168 (0.60%)	1
Influenza ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Neutropenic sepsis ^† 1	4/335 (1.19%)	6	0/168 (0.00%)	0
Peritonitis bacterial ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	2
Pneumonia ^† 1	4/335 (1.19%)	4	2/168 (1.19%)	2
Salmonellosis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Sepsis ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Septic shock ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Typhoid fever ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Upper respiratory tract infection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Urinary tract infection ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Urosepsis ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Injury, poisoning and procedural complications
Accidental overdose ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Clavicle fracture ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Thoracic vertebral fracture ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Investigations
Bilirubin conjugated increased ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Blood bilirubin increased ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Neutrophil count decreased ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
White blood cell count decreased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Metabolism and nutrition disorders
Alkalosis hypochloraemic ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cachexia ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Decreased appetite ^† 1	11/335 (3.28%)	11	4/168 (2.38%)	4
Dehydration ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Failure to thrive ^† 1	2/335 (0.60%)	2	1/168 (0.60%)	1
Hypoalbuminaemia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hypoglycaemia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hyponatraemia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/335 (0.00%)	0	3/168 (1.79%)	3
Joint swelling ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cancer pain ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Lymphangiosis carcinomatosa ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Malignant ascites ^† 1	1/335 (0.30%)	1	2/168 (1.19%)	2
Metastases to central nervous system ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Neoplasm malignant ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Tumour haemorrhage ^† 1	2/335 (0.60%)	2	1/168 (0.60%)	1
Ureteric cancer metastatic ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Nervous system disorders
Altered state of consciousness ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cerebral haemorrhage ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cerebral infarction ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cerebrovascular accident ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Depressed level of consciousness ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Headache ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hemiparesis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Ischaemic stroke ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Presyncope ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Transient ischaemic attack ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hydronephrosis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Renal failure ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Reproductive system and breast disorders
Breast pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Endometrial hyperplasia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	4/335 (1.19%)	4	2/168 (1.19%)	2
Pleural effusion ^† 1	5/335 (1.49%)	6	1/168 (0.60%)	1
Pneumonia aspiration ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Pulmonary embolism ^† 1	5/335 (1.49%)	5	2/168 (1.19%)	2
Respiratory failure ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Vascular disorders
Hypotension ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Lymphoedema ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Shock haemorrhagic ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Venous thrombosis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
1 Term from vocabulary, MedDRA 20.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	TAS-102+BSC		Placebo+BSC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	319/335 (95.22%)		151/168 (89.88%)
Blood and lymphatic system disorders
Anaemia ^† 1	142/335 (42.39%)	249	30/168 (17.86%)	52
Bone marrow failure ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Disseminated intravascular coagulation ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Febrile neutropenia ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Leukopenia ^† 1	57/335 (17.01%)	116	3/168 (1.79%)	14
Lymph node pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Lymphadenopathy ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Lymphopenia ^† 1	20/335 (5.97%)	42	8/168 (4.76%)	21
Neutropenia ^† 1	128/335 (38.21%)	312	6/168 (3.57%)	9
Neutrophilia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Pancytopenia ^† 1	1/335 (0.30%)	3	0/168 (0.00%)	0
Thrombocytopenia ^† 1	32/335 (9.55%)	45	2/168 (1.19%)	2
Cardiac disorders
Angina pectoris ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Atrial flutter ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Atrial tachycardia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Bradycardia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cardiac disorder ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Cardiovascular insufficiency ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Mitral valve incompetence ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Palpitations ^† 1	6/335 (1.79%)	6	2/168 (1.19%)	2
Pericardial effusion ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Sinus tachycardia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Tachycardia ^† 1	2/335 (0.60%)	3	2/168 (1.19%)	2
Congenital, familial and genetic disorders
Hydrocele ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Ear and labyrinth disorders
Ear discomfort ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Ear pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Vertigo ^† 1	3/335 (0.90%)	3	1/168 (0.60%)	1
Eye disorders
Dry eye ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Eye irritation ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Eye pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Eye pruritus ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Lacrimation increased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Visual impairment ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Gastrointestinal disorders
Abdominal discomfort ^† 1	3/335 (0.90%)	4	1/168 (0.60%)	1
Abdominal distension ^† 1	13/335 (3.88%)	15	9/168 (5.36%)	9
Abdominal pain ^† 1	50/335 (14.93%)	75	27/168 (16.07%)	34
Abdominal pain lower ^† 1	3/335 (0.90%)	3	2/168 (1.19%)	2
Abdominal pain upper ^† 1	22/335 (6.57%)	27	14/168 (8.33%)	15
Anal inflammation ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Anal pruritus ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Aphthous ulcer ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Ascites ^† 1	16/335 (4.78%)	24	10/168 (5.95%)	18
Cheilitis ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Constipation ^† 1	44/335 (13.13%)	53	25/168 (14.88%)	31
Diarrhoea ^† 1	73/335 (21.79%)	118	24/168 (14.29%)	28
Dry mouth ^† 1	3/335 (0.90%)	3	4/168 (2.38%)	4
Dyschezia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Dyspepsia ^† 1	5/335 (1.49%)	7	3/168 (1.79%)	4
Dysphagia ^† 1	14/335 (4.18%)	16	6/168 (3.57%)	6
Epigastric discomfort ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Eructation ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Faeces discoloured ^† 1	1/335 (0.30%)	1	2/168 (1.19%)	2
Flatulence ^† 1	2/335 (0.60%)	4	2/168 (1.19%)	2
Gastric haemorrhage ^† 1	0/335 (0.00%)	0	2/168 (1.19%)	2
Gastric stenosis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Gastrointestinal haemorrhage ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Gastrooesophageal reflux disease ^† 1	4/335 (1.19%)	5	2/168 (1.19%)	2
Haematemesis ^† 1	3/335 (0.90%)	4	0/168 (0.00%)	0
Haematochezia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Haemorrhoidal haemorrhage ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Haemorrhoids ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Ileus ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Impaired gastric emptying ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Intestinal obstruction ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Intra-Abdominal fluid collection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Lower gastrointestinal haemorrhage ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Melaena ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Mouth haemorrhage ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Nausea ^† 1	123/335 (36.72%)	201	53/168 (31.55%)	64
Obstruction gastric ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Odynophagia ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Oesophageal pain ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Proctalgia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Rectal haemorrhage ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Small intestinal obstruction ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Stomatitis ^† 1	15/335 (4.48%)	17	3/168 (1.79%)	3
Toothache ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Upper gastrointestinal haemorrhage ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Vomiting ^† 1	80/335 (23.88%)	104	34/168 (20.24%)	48
General disorders
Asthenia ^† 1	65/335 (19.40%)	97	37/168 (22.02%)	45
Catheter site pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Chest discomfort ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Chest pain ^† 1	3/335 (0.90%)	3	1/168 (0.60%)	1
Chills ^† 1	4/335 (1.19%)	6	0/168 (0.00%)	0
Drug intolerance ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Early satiety ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Face oedema ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Facial pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Fatigue ^† 1	87/335 (25.97%)	136	35/168 (20.83%)	41
Feeling abnormal ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Feeling cold ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Feeling hot ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Gait disturbance ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
General physical health deterioration ^† 1	3/335 (0.90%)	3	3/168 (1.79%)	4
Hyperthermia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hypothermia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Localised oedema ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Malaise ^† 1	9/335 (2.69%)	16	8/168 (4.76%)	8
Mucosal inflammation ^† 1	8/335 (2.39%)	11	3/168 (1.79%)	3
Non-Cardiac chest pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Oedema ^† 1	8/335 (2.39%)	8	2/168 (1.19%)	2
Oedema peripheral ^† 1	17/335 (5.07%)	17	12/168 (7.14%)	12
Pain ^† 1	5/335 (1.49%)	6	8/168 (4.76%)	8
Performance status decreased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Peripheral swelling ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Pyrexia ^† 1	23/335 (6.87%)	37	8/168 (4.76%)	9
Hepatobiliary disorders
Biliary colic ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Cholecystitis acute ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Hepatic failure ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Hepatic function abnormal ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hepatic pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hepatomegaly ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Hyperbilirubinaemia ^† 1	10/335 (2.99%)	10	3/168 (1.79%)	5
Hypertransaminasaemia ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Jaundice ^† 1	2/335 (0.60%)	2	2/168 (1.19%)	2
Liver disorder ^† 1	4/335 (1.19%)	6	0/168 (0.00%)	0
Portal vein thrombosis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Immune system disorders
Autoimmune disorder ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	2
Perfume sensitivity ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Infections and infestations
Angular cheilitis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Bacterial infection ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Bronchitis ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Candida infection ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Cellulitis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Clostridium difficile infection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Conjunctivitis ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Cystitis ^† 1	3/335 (0.90%)	4	0/168 (0.00%)	0
Erysipelas ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Gastrointestinal infection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Gingival abscess ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Gingivitis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Herpes virus infection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Herpes zoster ^† 1	2/335 (0.60%)	2	1/168 (0.60%)	1
Influenza ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Laryngitis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Localised infection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Lower respiratory tract infection ^† 1	3/335 (0.90%)	4	0/168 (0.00%)	0
Lung infection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Nasopharyngitis ^† 1	5/335 (1.49%)	5	0/168 (0.00%)	0
Oesophageal candidiasis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Oral candidiasis ^† 1	6/335 (1.79%)	6	2/168 (1.19%)	2
Pneumonia ^† 1	4/335 (1.19%)	4	1/168 (0.60%)	1
Pyuria ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Respiratory tract infection ^† 1	3/335 (0.90%)	3	2/168 (1.19%)	2
Rhinitis ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Sinusitis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Skin infection ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Staphylococcal infection ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Tonsillitis ^† 1	2/335 (0.60%)	3	0/168 (0.00%)	0
Tracheobronchitis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Upper respiratory tract infection ^† 1	8/335 (2.39%)	9	0/168 (0.00%)	0
Urinary tract infection ^† 1	9/335 (2.69%)	15	4/168 (2.38%)	4
Urinary tract infection bacterial ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Vulvovaginal candidiasis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Injury, poisoning and procedural complications
Accidental overdose ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Fall ^† 1	3/335 (0.90%)	3	3/168 (1.79%)	4
Foreign body in gastrointestinal tract ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Procedural pain ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Radiation injury ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Transfusion reaction ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Investigations
Alanine aminotransferase ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Alanine aminotransferase increased ^† 1	16/335 (4.78%)	17	8/168 (4.76%)	8
Aspartate aminotransferase ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Aspartate aminotransferase increased ^† 1	21/335 (6.27%)	26	13/168 (7.74%)	15
Bilirubin conjugated increased ^† 1	1/335 (0.30%)	2	1/168 (0.60%)	1
Blood alkaline phosphatase ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Blood alkaline phosphatase increased ^† 1	30/335 (8.96%)	35	14/168 (8.33%)	15
Blood bilirubin ^† 1	1/335 (0.30%)	3	0/168 (0.00%)	0
Blood bilirubin increased ^† 1	17/335 (5.07%)	27	7/168 (4.17%)	9
Blood bilirubin unconjugated increased ^† 1	1/335 (0.30%)	2	1/168 (0.60%)	1
Blood creatinine decreased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Blood creatinine increased ^† 1	10/335 (2.99%)	11	6/168 (3.57%)	11
Blood iron decreased ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Blood potassium increased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Blood urea increased ^† 1	7/335 (2.09%)	9	7/168 (4.17%)	8
Creatinine renal clearance decreased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Enzyme level increased ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Gamma-Glutamyltransferase increased ^† 1	4/335 (1.19%)	6	5/168 (2.98%)	6
Haematocrit decreased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Haemoglobin decreased ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Hepatic enzyme increased ^† 1	3/335 (0.90%)	4	0/168 (0.00%)	0
International normalised ratio increased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Liver function test increased ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Lymphocyte count decreased ^† 1	2/335 (0.60%)	7	0/168 (0.00%)	0
Neutrophil count ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Neutrophil count decreased ^† 1	50/335 (14.93%)	139	1/168 (0.60%)	1
Platelet count decreased ^† 1	28/335 (8.36%)	43	6/168 (3.57%)	11
Platelet count increased ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Protein total decreased ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Red blood cell count decreased ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Red cell distribution width increased ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Vital capacity abnormal ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Weight decreased ^† 1	20/335 (5.97%)	21	12/168 (7.14%)	13
Weight increased ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
White blood cell count decreased ^† 1	23/335 (6.87%)	59	0/168 (0.00%)	0
Metabolism and nutrition disorders
Cachexia ^† 1	3/335 (0.90%)	3	1/168 (0.60%)	1
Decreased appetite ^† 1	109/335 (32.54%)	164	49/168 (29.17%)	54
Dehydration ^† 1	4/335 (1.19%)	6	2/168 (1.19%)	2
Electrolyte imbalance ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Feeding intolerance ^† 1	1/335 (0.30%)	2	0/168 (0.00%)	0
Hypercalcaemia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Hypercreatininaemia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Hyperglycaemia ^† 1	9/335 (2.69%)	10	5/168 (2.98%)	5
Hyperkalaemia ^† 1	1/335 (0.30%)	3	3/168 (1.79%)	5
Hyperuricaemia ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Hypoalbuminaemia ^† 1	21/335 (6.27%)	28	10/168 (5.95%)	11
Hypocalcaemia ^† 1	9/335 (2.69%)	11	1/168 (0.60%)	3
Hypokalaemia ^† 1	9/335 (2.69%)	11	3/168 (1.79%)	3
Hypomagnesaemia ^† 1	7/335 (2.09%)	7	3/168 (1.79%)	3
Hyponatraemia ^† 1	5/335 (1.49%)	6	7/168 (4.17%)	8
Hypophagia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hypophosphataemia ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	2
Hypoproteinaemia ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Iron deficiency ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Malnutrition ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Vitamin d deficiency ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	6/335 (1.79%)	7	2/168 (1.19%)	3
Back pain ^† 1	25/335 (7.46%)	31	9/168 (5.36%)	10
Bone pain ^† 1	3/335 (0.90%)	4	0/168 (0.00%)	0
Bone swelling ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Flank pain ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	2
Groin pain ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Intervertebral disc compression ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Intervertebral disc disorder ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Limb discomfort ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Muscle atrophy ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Muscle spasms ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Muscular weakness ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Musculoskeletal chest pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Musculoskeletal pain ^† 1	5/335 (1.49%)	6	2/168 (1.19%)	2
Musculoskeletal stiffness ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Myalgia ^† 1	4/335 (1.19%)	5	0/168 (0.00%)	0
Neck pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Osteoarthritis ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Osteoporosis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Pain in extremity ^† 1	3/335 (0.90%)	5	1/168 (0.60%)	2
Soft tissue disorder ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Spinal pain ^† 1	2/335 (0.60%)	2	2/168 (1.19%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain ^† 1	3/335 (0.90%)	3	1/168 (0.60%)	1
Lipoma ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Malignant ascites ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Skin papilloma ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Tumour associated fever ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Tumour pain ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Nervous system disorders
Agnosia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Amnesia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Burning sensation ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Dizziness ^† 1	8/335 (2.39%)	10	4/168 (2.38%)	4
Dysgeusia ^† 1	11/335 (3.28%)	17	1/168 (0.60%)	1
Encephalopathy ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Headache ^† 1	6/335 (1.79%)	8	4/168 (2.38%)	5
Lethargy ^† 1	2/335 (0.60%)	2	3/168 (1.79%)	3
Monoplegia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Myoclonus ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Neuralgia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Neuropathy peripheral ^† 1	4/335 (1.19%)	4	1/168 (0.60%)	1
Paraesthesia ^† 1	8/335 (2.39%)	8	0/168 (0.00%)	0
Peripheral sensory neuropathy ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Peroneal nerve palsy ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Sciatica ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Somnolence ^† 1	5/335 (1.49%)	5	1/168 (0.60%)	1
Transient ischaemic attack ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Product Issues
Device dislocation ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Psychiatric disorders
Agitation ^† 1	2/335 (0.60%)	2	2/168 (1.19%)	2
Anxiety ^† 1	9/335 (2.69%)	9	4/168 (2.38%)	4
Confusional state ^† 1	2/335 (0.60%)	3	3/168 (1.79%)	3
Delirium ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Depression ^† 1	3/335 (0.90%)	5	2/168 (1.19%)	2
Disturbance in social behaviour ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Drug abuse ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hallucination ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Insomnia ^† 1	11/335 (3.28%)	12	10/168 (5.95%)	10
Nervousness ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	2/335 (0.60%)	4	1/168 (0.60%)	1
Albuminuria ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Choluria ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Dysuria ^† 1	5/335 (1.49%)	5	3/168 (1.79%)	3
Haematuria ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Hydronephrosis ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Leukocyturia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Microalbuminuria ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Micturition disorder ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Nocturia ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Pollakiuria ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Proteinuria ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Renal colic ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Renal pain ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Urinary incontinence ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Urinary retention ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Reproductive system and breast disorders
Breast pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Endometrial hyperplasia ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Pelvic discomfort ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Pelvic pain ^† 1	1/335 (0.30%)	1	2/168 (1.19%)	2
Vaginal haemorrhage ^† 1	0/335 (0.00%)	0	3/168 (1.79%)	3
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	11/335 (3.28%)	12	6/168 (3.57%)	7
Dysphonia ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Dyspnoea ^† 1	21/335 (6.27%)	24	16/168 (9.52%)	16
Dyspnoea exertional ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Epistaxis ^† 1	4/335 (1.19%)	5	1/168 (0.60%)	1
Hiccups ^† 1	4/335 (1.19%)	4	5/168 (2.98%)	5
Nasal congestion ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Oropharyngeal pain ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Pleural effusion ^† 1	10/335 (2.99%)	11	4/168 (2.38%)	4
Pleurisy ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Pleuritic pain ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Pneumonia aspiration ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Productive cough ^† 1	4/335 (1.19%)	4	1/168 (0.60%)	1
Pulmonary embolism ^† 1	5/335 (1.49%)	5	1/168 (0.60%)	1
Respiratory disorder ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Rhinitis allergic ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Rhinorrhoea ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Sputum discoloured ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Tachypnoea ^† 1	0/335 (0.00%)	0	2/168 (1.19%)	2
Upper respiratory tract inflammation ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Wheezing ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Skin and subcutaneous tissue disorders
Acne ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Alopecia ^† 1	12/335 (3.58%)	14	1/168 (0.60%)	1
Blister ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Decubitus ulcer ^† 1	2/335 (0.60%)	2	1/168 (0.60%)	1
Dermatitis ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Dermatitis allergic ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Dry skin ^† 1	5/335 (1.49%)	5	1/168 (0.60%)	1
Hand dermatitis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Hyperhidrosis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Nail discolouration ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	1
Nail disorder ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Night sweats ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Onychoclasis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Palmar-Plantar erythrodysaesthesia syndrome ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Petechiae ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Pruritus ^† 1	8/335 (2.39%)	9	2/168 (1.19%)	2
Rash ^† 1	4/335 (1.19%)	5	1/168 (0.60%)	1
Rash maculo-papular ^† 1	0/335 (0.00%)	0	1/168 (0.60%)	4
Skin lesion ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Urticaria ^† 1	1/335 (0.30%)	1	1/168 (0.60%)	1
Xeroderma ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Vascular disorders
Deep vein thrombosis ^† 1	2/335 (0.60%)	2	1/168 (0.60%)	1
Embolism ^† 1	2/335 (0.60%)	2	0/168 (0.00%)	0
Hot flush ^† 1	0/335 (0.00%)	0	2/168 (1.19%)	2
Hypertension ^† 1	3/335 (0.90%)	3	0/168 (0.00%)	0
Hypotension ^† 1	7/335 (2.09%)	7	1/168 (0.60%)	1
Pallor ^† 1	2/335 (0.60%)	4	0/168 (0.00%)	0
Phlebitis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Raynaud's phenomenon ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
Thrombophlebitis ^† 1	1/335 (0.30%)	1	0/168 (0.00%)	0
1 Term from vocabulary, MedDRA 20.1 † 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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Taiho Central
Organization:	Taiho Oncology, Inc.
Phone:	609-250-7336
EMail:	clinicaltrialinfo@taihooncology.com

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

Tabernero J, Alsina M, Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Ando T, Yalcin S, Van Cutsem E, Sabater J, Skanji D, Leger C, Amellal N, Ilson DH. Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS. Gastric Cancer. 2020 Jul;23(4):689-698. doi: 10.1007/s10120-020-01053-9. Epub 2020 Mar 4.

Ilson DH, Tabernero J, Prokharau A, Arkenau HT, Ghidini M, Fujitani K, Van Cutsem E, Thuss-Patience P, Beretta GD, Mansoor W, Zhavrid E, Alsina M, George B, Catenacci D, McGuigan S, Makris L, Doi T, Shitara K. Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy: Subgroup Analyses of a Randomized Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):e193531. doi: 10.1001/jamaoncol.2019.3531. Epub 2020 Jan 9.

Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalcin S, Fujitani K, Beretta GD, Cutsem EV, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov;19(11):1437-1448. doi: 10.1016/S1470-2045(18)30739-3. Epub 2018 Oct 21. Erratum In: Lancet Oncol. 2018 Dec;19(12):e668.

Bando H, Doi T, Muro K, Yasui H, Nishina T, Yamaguchi K, Takahashi S, Nomura S, Kuno H, Shitara K, Sato A, Ohtsu A. A multicenter phase II study of TAS-102 monotherapy in patients with pre-treated advanced gastric cancer (EPOC1201). Eur J Cancer. 2016 Jul;62:46-53. doi: 10.1016/j.ejca.2016.04.009. Epub 2016 May 19.

Layout table for additonal information

Responsible Party:	Taiho Oncology, Inc.
ClinicalTrials.gov Identifier:	NCT02500043
Other Study ID Numbers:	TO-TAS-102-302 2015-002683-16 ( EudraCT Number )
First Submitted:	July 13, 2015
First Posted:	July 16, 2015
Results First Submitted:	July 2, 2021
Results First Posted:	September 16, 2021
Last Update Posted:	September 16, 2021

To Top