Study of Participants With Advanced Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT00948675

Recruitment Status : Completed

First Posted : July 29, 2009

Results First Posted : April 2, 2014

Last Update Posted : October 29, 2021

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Sponsor:

Information provided by (Responsible Party):

Eli Lilly and Company

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Advanced Non-Small Cell Lung Cancer
Interventions	Drug: Pemetrexed Drug: Carboplatin Drug: Paclitaxel Biological: Bevacizumab
Enrollment	361

Participant Flow

Recruitment Details
Pre-assignment Details	Completers included participants who died, participants with progressive disease and those who got randomized but didn't receive any treatment.


Arm/Group Title	Pemetrexed + Carboplatin	Paclitaxel + Carboplatin + Bevacizumab
Arm/Group Description	Induction therapy: pemetrexed 500 m...	Induction therapy: paclitaxel 200 m...
Arm/Group Description	Induction therapy: pemetrexed 500 milligrams/square meter (mg/m²) given intravenously plus carboplatin area under the curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes for four 21-day cycles. Maintenance therapy: pemetrexed 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.	Induction therapy: paclitaxel 200 mg/m² intravenously infused over 3 hours plus carboplatin AUC 6 (maximum possible dose of 900 mg) intravenously infused over 30 minutes plus bevacizumab 15 milligrams/kilogram (mg/kg) given intravenously for four 21-day cycles. Maintenance therapy: bevacizumab 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.
Period Title: Overall Study
Started	182	179
Received Any Amount of Study Drug	171	166
Completed	181	179
Not Completed	1	0
Reason Not Completed
Lost to Follow-up	1	0

Baseline Characteristics

Arm/Group Title		Pemetrexed + Carboplatin	Paclitaxel + Carboplatin + Bevacizumab	Total
Arm/Group Description		Induction therapy: pemetrexed 500 m...	Induction therapy: paclitaxel 200 m...	Total of all reporting groups
Arm/Group Description		Induction therapy: pemetrexed 500 milligrams/square meter (mg/m²) given intravenously plus carboplatin area under the curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes for four 21-day cycles. Maintenance therapy: pemetrexed 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.	Induction therapy: paclitaxel 200 mg/m² intravenously infused over 3 hours plus carboplatin AUC 6 (maximum possible dose of 900 mg) intravenously infused over 30 minutes plus bevacizumab 15 milligrams/kilogram (mg/kg) given intravenously for four 21-day cycles. Maintenance therapy: bevacizumab 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.	Total of all reporting groups
Overall Number of Baseline Participants		182	179	361
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All randomized participants.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	182 participants	179 participants	361 participants
		64.8 (9.62)	64.6 (8.82)	64.7 (9.22)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	182 participants	179 participants	361 participants
	Female	77	75	152
	Male	105	104	209
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	182 participants	179 participants	361 participants
	Hispanic or Latino	4	5	9
	Not Hispanic or Latino	178	174	352
	Unknown or Not Reported	0	0	0
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	182 participants	179 participants	361 participants
	American Indian or Alaska Native	0	2	2
	Asian	4	0	4
	Native Hawaiian or Other Pacific Islander	0	0	0
	Black or African American	11	20	31
	White	165	157	322
	More than one race	2	0	2
	Unknown or Not Reported	0	0	0
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	182 participants	179 participants	361 participants
United States		182	179	361

Outcome Measures

1.Primary Outcome


Title	Progression Free Survival Without Grade 4 Toxicity (G4PFS) as Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Description	G4PFS was defined as the duration from the date of randomization to th...
Description	G4PFS was defined as the duration from the date of randomization to the earliest occurrence date of one of the following three events: Common Terminology Criteria (CTC) grade 4 adverse events (G4AEs), or progressive disease (PD) or death from any cause, whichever occurred earlier. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no G4AEs, or PD, or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy.
Time Frame	Randomization to measured progressive disease or treatment discontinuation up to 39.49 months

Outcome Measure Data

Analysis Population Description

All randomized participants. The number of participants censored was 30 for pemetrexed + carboplatin group and 35 for paclitaxel + carboplatin + bevacizumab group.


Arm/Group Title	Pemetrexed + Carboplatin	Paclitaxel + Carboplatin + Bevacizumab
Arm/Group Description:	Induction therapy: pemetrexed 500 m...	Induction therapy: paclitaxel 200 m...
Arm/Group Description:	Induction therapy: pemetrexed 500 milligrams/square meter (mg/m²) given intravenously plus carboplatin area under the curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes for four 21-day cycles. Maintenance therapy: pemetrexed 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.	Induction therapy: paclitaxel 200 mg/m² intravenously infused over 3 hours plus carboplatin AUC 6 (maximum possible dose of 900 mg) intravenously infused over 30 minutes plus bevacizumab 15 milligrams/kilogram (mg/kg) given intravenously for four 21-day cycles. Maintenance therapy: bevacizumab 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.
Overall Number of Participants Analyzed	182	179
Median (90% Confidence Interval) Unit of Measure: months
	3.91 (2.73 to 4.37)	2.86 (2.20 to 4.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed + Carboplatin, Paclitaxel + Carboplatin + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.176
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

2.Secondary Outcome


Title	Progression Free Survival (PFS)
Description	PFS was defined as the duration from the date of randomization to the ...
Description	PFS was defined as the duration from the date of randomization to the date of progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD was ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy.
Time Frame	Randomization to measured progressive disease up to 39.49 months

Outcome Measure Data

Analysis Population Description

All randomized participants. The number of participants censored was 35 for pemetrexed + carboplatin group and 49 for paclitaxel + carboplatin + bevacizumab group.


Arm/Group Title	Pemetrexed + Carboplatin	Paclitaxel + Carboplatin + Bevacizumab
Arm/Group Description:	Induction therapy: pemetrexed 500 m...	Induction therapy: paclitaxel 200 m...
Arm/Group Description:	Induction therapy: pemetrexed 500 milligrams/square meter (mg/m²) given intravenously plus carboplatin area under the curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes for four 21-day cycles. Maintenance therapy: pemetrexed 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.	Induction therapy: paclitaxel 200 mg/m² intravenously infused over 3 hours plus carboplatin AUC 6 (maximum possible dose of 900 mg) intravenously infused over 30 minutes plus bevacizumab 15 milligrams/kilogram (mg/kg) given intravenously for four 21-day cycles. Maintenance therapy: bevacizumab 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.
Overall Number of Participants Analyzed	182	179
Median (90% Confidence Interval) Unit of Measure: months
	4.44 (4.21 to 5.32)	5.45 (5.03 to 5.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed + Carboplatin, Paclitaxel + Carboplatin + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.610
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

3.Secondary Outcome


Title	Overall Survival (OS)
Description	OS was defined as the duration from the date of randomization to the d...
Description	OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the last date the participant was known to be alive.
Time Frame	Randomization to date of death from any cause up to 39.49 months

Outcome Measure Data

Analysis Population Description

All randomized participants. The number of participants censored was 52 for pemetrexed + carboplatin group and 56 for paclitaxel + carboplatin + bevacizumab group.


Arm/Group Title	Pemetrexed + Carboplatin	Paclitaxel + Carboplatin + Bevacizumab
Arm/Group Description:	Induction therapy: pemetrexed 500 m...	Induction therapy: paclitaxel 200 m...
Arm/Group Description:	Induction therapy: pemetrexed 500 milligrams/square meter (mg/m²) given intravenously plus carboplatin area under the curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes for four 21-day cycles. Maintenance therapy: pemetrexed 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.	Induction therapy: paclitaxel 200 mg/m² intravenously infused over 3 hours plus carboplatin AUC 6 (maximum possible dose of 900 mg) intravenously infused over 30 minutes plus bevacizumab 15 milligrams/kilogram (mg/kg) given intravenously for four 21-day cycles. Maintenance therapy: bevacizumab 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.
Overall Number of Participants Analyzed	182	179
Median (90% Confidence Interval) Unit of Measure: months
	10.51 (9.26 to 11.96)	11.66 (9.17 to 14.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed + Carboplatin, Paclitaxel + Carboplatin + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.615
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

4.Secondary Outcome


Title	Percentage of Participants With Complete Response or Partial Response (Overall Tumor Response Rate)
Description	Overall Response rate (ORR) was the percentage of participants with a ...
Description	Overall Response rate (ORR) was the percentage of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR was the disappearance of all target and non-target lesions; PR was a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR was calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.
Time Frame	Baseline to date of objective progressive disease up to 39.49 months

Outcome Measure Data

Analysis Population Description

All randomized participants.


Arm/Group Title	Pemetrexed + Carboplatin	Paclitaxel + Carboplatin + Bevacizumab
Arm/Group Description:	Induction therapy: pemetrexed 500 m...	Induction therapy: paclitaxel 200 m...
Arm/Group Description:	Induction therapy: pemetrexed 500 milligrams/square meter (mg/m²) given intravenously plus carboplatin area under the curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes for four 21-day cycles. Maintenance therapy: pemetrexed 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.	Induction therapy: paclitaxel 200 mg/m² intravenously infused over 3 hours plus carboplatin AUC 6 (maximum possible dose of 900 mg) intravenously infused over 30 minutes plus bevacizumab 15 milligrams/kilogram (mg/kg) given intravenously for four 21-day cycles. Maintenance therapy: bevacizumab 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.
Overall Number of Participants Analyzed	182	179
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	23.6 (17.7 to 30.5)	27.4 (21.0 to 34.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed + Carboplatin, Paclitaxel + Carboplatin + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.414
	Comments	[Not Specified]
	Method	Pearson Chi-square Test
	Comments	[Not Specified]

5.Secondary Outcome


Title	Disease Control Rates Defined as Complete Response (CR), Partial Response (PR), and Stable Disease (SD)
Description	Disease control rate was the percentage of participants with a confirm...
Description	Disease control rate was the percentage of participants with a confirmed CR, PR or SD, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR was the disappearance of all target and non-target lesions; PR was a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion; SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Disease control rate was calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100.
Time Frame	Baseline to date of objective progressive disease up to 39.49 months

Outcome Measure Data

Analysis Population Description

All randomized participants.


Arm/Group Title	Pemetrexed + Carboplatin	Paclitaxel + Carboplatin + Bevacizumab
Arm/Group Description:	Induction therapy: pemetrexed 500 m...	Induction therapy: paclitaxel 200 m...
Arm/Group Description:	Induction therapy: pemetrexed 500 milligrams/square meter (mg/m²) given intravenously plus carboplatin area under the curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes for four 21-day cycles. Maintenance therapy: pemetrexed 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.	Induction therapy: paclitaxel 200 mg/m² intravenously infused over 3 hours plus carboplatin AUC 6 (maximum possible dose of 900 mg) intravenously infused over 30 minutes plus bevacizumab 15 milligrams/kilogram (mg/kg) given intravenously for four 21-day cycles. Maintenance therapy: bevacizumab 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.
Overall Number of Participants Analyzed	182	179
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	59.9 (52.4 to 67.1)	57.0 (49.4 to 64.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed + Carboplatin, Paclitaxel + Carboplatin + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.575
	Comments	[Not Specified]
	Method	Pearson Chi-square Test
	Comments	[Not Specified]

Adverse Events

Time Frame	Baseline to Follow-up (up to 9 years)
Adverse Event Reporting Description	Only those participants who received any amount of study drug were included in the safety analysis.

Arm/Group Title	Pemetrexed + Carboplatin		Paclitaxel + Carboplatin + Bevacizumab
Arm/Group Description	Induction therapy: pemetrexed 500 m...		Induction therapy: paclitaxel 200 m...
Arm/Group Description	Induction therapy: pemetrexed 500 milligrams/square meter (mg/m²) given intravenously plus carboplatin area under the curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes for four 21-day cycles. Maintenance therapy: pemetrexed 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.		Induction therapy: paclitaxel 200 mg/m² intravenously infused over 3 hours plus carboplatin AUC 6 (maximum possible dose of 900 mg) intravenously infused over 30 minutes plus bevacizumab 15 milligrams/kilogram (mg/ kg) given intravenously for four 21-day cycles. Maintenance therapy: bevacizumab 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.
All-Cause Mortality
	Pemetrexed + Carboplatin		Paclitaxel + Carboplatin + Bevacizumab
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Pemetrexed + Carboplatin		Paclitaxel + Carboplatin + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/171 (44.44%)		64/166 (38.55%)
Blood and lymphatic system disorders
Anaemia ^† 1	12/171 (7.02%)	33	2/166 (1.20%)	2
Febrile neutropenia ^† 1	0/171 (0.00%)	0	4/166 (2.41%)	4
Haemorrhagic anaemia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Leukopenia ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Neutropenia ^† 1	5/171 (2.92%)	5	5/166 (3.01%)	7
Thrombocytopenia ^† 1	4/171 (2.34%)	8	2/166 (1.20%)	2
Cardiac disorders
Angina unstable ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Atrial fibrillation ^† 1	2/171 (1.17%)	2	0/166 (0.00%)	0
Atrial flutter ^† 1	3/171 (1.75%)	4	1/166 (0.60%)	1
Bradycardia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Cardiac failure congestive ^† 1	1/171 (0.58%)	3	3/166 (1.81%)	13
Cardio-respiratory arrest ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Cardiomyopathy acute ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Coronary artery disease ^† 1	2/171 (1.17%)	11	0/166 (0.00%)	0
Myocardial infarction ^† 1	1/171 (0.58%)	1	1/166 (0.60%)	1
Nodal arrhythmia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Pericardial effusion ^† 1	2/171 (1.17%)	4	0/166 (0.00%)	0
Pericarditis ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Supraventricular tachycardia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Ventricular tachycardia ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Eye disorders
Blindness ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Gastrointestinal disorders
Abdominal pain ^† 1	2/171 (1.17%)	3	1/166 (0.60%)	2
Colitis ^† 1	1/171 (0.58%)	4	0/166 (0.00%)	0
Constipation ^† 1	1/171 (0.58%)	3	2/166 (1.20%)	3
Diarrhoea ^† 1	3/171 (1.75%)	4	6/166 (3.61%)	12
Diverticulum intestinal haemorrhagic ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Haematemesis ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Haematochezia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Large intestine perforation ^† 1	0/171 (0.00%)	0	2/166 (1.20%)	3
Nausea ^† 1	5/171 (2.92%)	7	9/166 (5.42%)	10
Oesophagitis ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Pancreatitis ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Rectal obstruction ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Small intestinal obstruction ^† 1	3/171 (1.75%)	4	1/166 (0.60%)	1
Vomiting ^† 1	3/171 (1.75%)	4	10/166 (6.02%)	12
General disorders
Asthenia ^† 1	4/171 (2.34%)	5	3/166 (1.81%)	5
Catheter site pain ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Chest pain ^† 1	5/171 (2.92%)	8	1/166 (0.60%)	1
Disease progression ^† 1	3/171 (1.75%)	4	0/166 (0.00%)	0
Mucosal inflammation ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Pain ^† 1	0/171 (0.00%)	0	3/166 (1.81%)	5
Pyrexia ^† 1	2/171 (1.17%)	2	2/166 (1.20%)	2
Hepatobiliary disorders
Hyperbilirubinaemia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Immune system disorders
Hypersensitivity ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Infections and infestations
Cellulitis ^† 1	2/171 (1.17%)	5	1/166 (0.60%)	3
Clostridium difficile colitis ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Device related infection ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Device related sepsis ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Diverticulitis ^† 1	0/171 (0.00%)	0	2/166 (1.20%)	6
Osteomyelitis ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	15
Pneumonia ^† 1	14/171 (8.19%)	18	6/166 (3.61%)	13
Pneumonia mycoplasmal ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Psoas abscess ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	15
Sepsis ^† 1	1/171 (0.58%)	1	1/166 (0.60%)	1
Urinary tract infection ^† 1	1/171 (0.58%)	4	3/166 (1.81%)	3
Injury, poisoning and procedural complications
Cervical vertebral fracture ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Clavicle fracture ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Fall ^† 1	1/171 (0.58%)	1	1/166 (0.60%)	1
Femur fracture ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Overdose ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Pelvic fracture ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	3
Spinal compression fracture ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Toxicity to various agents ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Investigations
Blood creatinine increased ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Haemoglobin decreased ^† 1	3/171 (1.75%)	5	0/166 (0.00%)	0
Platelet count decreased ^† 1	2/171 (1.17%)	3	0/166 (0.00%)	0
Troponin increased ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Weight decreased ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Metabolism and nutrition disorders
Dehydration ^† 1	9/171 (5.26%)	11	11/166 (6.63%)	15
Failure to thrive ^† 1	1/171 (0.58%)	1	1/166 (0.60%)	2
Hypercalcaemia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Hyperglycaemia ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Hypoalbuminaemia ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Hypocalcaemia ^† 1	1/171 (0.58%)	1	2/166 (1.20%)	4
Hypokalaemia ^† 1	2/171 (1.17%)	2	2/166 (1.20%)	5
Hyponatraemia ^† 1	1/171 (0.58%)	1	1/166 (0.60%)	1
Hypovolaemia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Lactic acidosis ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Back pain ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	3
Bone lesion ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Bone pain ^† 1	1/171 (0.58%)	7	0/166 (0.00%)	0
Groin pain ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Hypertrophic osteoarthropathy ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Muscular weakness ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Musculoskeletal chest pain ^† 1	1/171 (0.58%)	2	2/166 (1.20%)	3
Neck pain ^† 1	1/171 (0.58%)	2	1/166 (0.60%)	1
Pathological fracture ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant ^† 1	1/171 (0.58%)	7	0/166 (0.00%)	0
Malignant pleural effusion ^† 1	2/171 (1.17%)	3	0/166 (0.00%)	0
Metastases to meninges ^† 1	0/171 (0.00%)	0	2/166 (1.20%)	4
Metastatic neoplasm ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Neoplasm ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Tumour pain ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Nervous system disorders
Autonomic nervous system imbalance ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	4
Cerebral ischaemia ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Cerebrovascular accident ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Depressed level of consciousness ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Dizziness ^† 1	1/171 (0.58%)	1	1/166 (0.60%)	3
Embolic stroke ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Headache ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Lacunar infarction ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	4
Neuropathy peripheral ^† 1	0/171 (0.00%)	0	2/166 (1.20%)	5
Spinal cord compression ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Syncope ^† 1	3/171 (1.75%)	3	2/166 (1.20%)	3
Transient ischaemic attack ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Psychiatric disorders
Confusional state ^† 1	2/171 (1.17%)	3	0/166 (0.00%)	0
Emotional distress ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Mental status changes ^† 1	0/171 (0.00%)	0	3/166 (1.81%)	4
Psychotic disorder ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	1
Suicidal ideation ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Renal and urinary disorders
Haematuria ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Nephrotic syndrome ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Renal failure ^† 1	2/171 (1.17%)	3	1/166 (0.60%)	1
Renal failure acute ^† 1	4/171 (2.34%)	4	1/166 (0.60%)	2
Urinary retention ^† 1	1/171 (0.58%)	2	1/166 (0.60%)	3
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^† 1	2/171 (1.17%)	2	0/166 (0.00%)	0
Aspiration ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Chronic obstructive pulmonary disease ^† 1	4/171 (2.34%)	40	2/166 (1.20%)	8
Dyspnoea ^† 1	6/171 (3.51%)	13	4/166 (2.41%)	10
Dyspnoea exertional ^† 1	1/171 (0.58%)	5	0/166 (0.00%)	0
Epistaxis ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Haemoptysis ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	3
Hydropneumothorax ^† 1	1/171 (0.58%)	2	0/166 (0.00%)	0
Hypoxia ^† 1	0/171 (0.00%)	0	3/166 (1.81%)	3
Pleural effusion ^† 1	3/171 (1.75%)	4	3/166 (1.81%)	10
Pneumothorax ^† 1	1/171 (0.58%)	1	1/166 (0.60%)	1
Pulmonary embolism ^† 1	8/171 (4.68%)	22	5/166 (3.01%)	7
Respiratory failure ^† 1	3/171 (1.75%)	4	4/166 (2.41%)	5
Stridor ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Vascular disorders
Deep vein thrombosis ^† 1	3/171 (1.75%)	15	3/166 (1.81%)	3
Embolism ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Haematoma ^† 1	1/171 (0.58%)	1	1/166 (0.60%)	2
Haemorrhage ^† 1	1/171 (0.58%)	1	0/166 (0.00%)	0
Hypertension ^† 1	0/171 (0.00%)	0	1/166 (0.60%)	2
Hypotension ^† 1	4/171 (2.34%)	5	4/166 (2.41%)	7
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 15.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pemetrexed + Carboplatin		Paclitaxel + Carboplatin + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	167/171 (97.66%)		160/166 (96.39%)
Blood and lymphatic system disorders
Anaemia ^† 1	92/171 (53.80%)	599	59/166 (35.54%)	380
Leukopenia ^† 1	39/171 (22.81%)	152	32/166 (19.28%)	89
Neutropenia ^† 1	57/171 (33.33%)	204	80/166 (48.19%)	270
Thrombocytopenia ^† 1	68/171 (39.77%)	329	47/166 (28.31%)	154
Eye disorders
Lacrimation increased ^† 1	14/171 (8.19%)	107	1/166 (0.60%)	4
Gastrointestinal disorders
Abdominal pain ^† 1	14/171 (8.19%)	49	14/166 (8.43%)	29
Constipation ^† 1	74/171 (43.27%)	481	68/166 (40.96%)	428
Diarrhoea ^† 1	30/171 (17.54%)	108	49/166 (29.52%)	263
Dyspepsia ^† 1	19/171 (11.11%)	157	15/166 (9.04%)	75
Dysphagia ^† 1	4/171 (2.34%)	25	10/166 (6.02%)	24
Gastrooesophageal reflux disease ^† 1	5/171 (2.92%)	51	10/166 (6.02%)	121
Nausea ^† 1	102/171 (59.65%)	610	69/166 (41.57%)	268
Stomatitis ^† 1	14/171 (8.19%)	72	15/166 (9.04%)	46
Vomiting ^† 1	49/171 (28.65%)	162	32/166 (19.28%)	83
General disorders
Asthenia ^† 1	9/171 (5.26%)	30	20/166 (12.05%)	147
Chest pain ^† 1	17/171 (9.94%)	62	12/166 (7.23%)	37
Chills ^† 1	12/171 (7.02%)	21	8/166 (4.82%)	18
Fatigue ^† 1	107/171 (62.57%)	1045	87/166 (52.41%)	827
Mucosal inflammation ^† 1	11/171 (6.43%)	39	17/166 (10.24%)	95
Oedema peripheral ^† 1	34/171 (19.88%)	481	12/166 (7.23%)	71
Pain ^† 1	8/171 (4.68%)	28	9/166 (5.42%)	64
Pyrexia ^† 1	15/171 (8.77%)	17	11/166 (6.63%)	15
Infections and infestations
Bronchitis ^† 1	5/171 (2.92%)	19	12/166 (7.23%)	21
Pneumonia ^† 1	10/171 (5.85%)	17	6/166 (3.61%)	20
Sinusitis ^† 1	12/171 (7.02%)	38	12/166 (7.23%)	31
Upper respiratory tract infection ^† 1	9/171 (5.26%)	18	5/166 (3.01%)	9
Urinary tract infection ^† 1	20/171 (11.70%)	34	10/166 (6.02%)	14
Investigations
Alanine aminotransferase increased ^† 1	14/171 (8.19%)	58	7/166 (4.22%)	29
Aspartate aminotransferase increased ^† 1	14/171 (8.19%)	51	7/166 (4.22%)	15
Blood creatinine increased ^† 1	14/171 (8.19%)	56	4/166 (2.41%)	5
Haemoglobin decreased ^† 1	23/171 (13.45%)	120	8/166 (4.82%)	51
Neutrophil count decreased ^† 1	12/171 (7.02%)	43	20/166 (12.05%)	53
Platelet count decreased ^† 1	20/171 (11.70%)	66	8/166 (4.82%)	43
Weight decreased ^† 1	15/171 (8.77%)	88	30/166 (18.07%)	155
White blood cell count decreased ^† 1	8/171 (4.68%)	20	12/166 (7.23%)	25
Metabolism and nutrition disorders
Decreased appetite ^† 1	52/171 (30.41%)	281	53/166 (31.93%)	310
Dehydration ^† 1	22/171 (12.87%)	48	20/166 (12.05%)	66
Hyperglycaemia ^† 1	33/171 (19.30%)	356	22/166 (13.25%)	104
Hypokalaemia ^† 1	24/171 (14.04%)	61	15/166 (9.04%)	41
Hypomagnesaemia ^† 1	21/171 (12.28%)	142	24/166 (14.46%)	86
Hyponatraemia ^† 1	17/171 (9.94%)	79	17/166 (10.24%)	85
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	21/171 (12.28%)	149	38/166 (22.89%)	285
Back pain ^† 1	19/171 (11.11%)	164	15/166 (9.04%)	90
Bone pain ^† 1	5/171 (2.92%)	38	17/166 (10.24%)	114
Musculoskeletal chest pain ^† 1	12/171 (7.02%)	68	6/166 (3.61%)	19
Musculoskeletal pain ^† 1	10/171 (5.85%)	46	11/166 (6.63%)	95
Myalgia ^† 1	10/171 (5.85%)	70	22/166 (13.25%)	134
Pain in extremity ^† 1	13/171 (7.60%)	95	19/166 (11.45%)	88
Nervous system disorders
Dizziness ^† 1	27/171 (15.79%)	148	20/166 (12.05%)	64
Dysgeusia ^† 1	20/171 (11.70%)	142	25/166 (15.06%)	128
Headache ^† 1	23/171 (13.45%)	170	25/166 (15.06%)	213
Neuropathy peripheral ^† 1	9/171 (5.26%)	33	36/166 (21.69%)	329
Peripheral sensory neuropathy ^† 1	9/171 (5.26%)	83	28/166 (16.87%)	251
Psychiatric disorders
Anxiety ^† 1	17/171 (9.94%)	117	13/166 (7.83%)	108
Depression ^† 1	12/171 (7.02%)	160	9/166 (5.42%)	63
Insomnia ^† 1	35/171 (20.47%)	330	31/166 (18.67%)	251
Renal and urinary disorders
Proteinuria ^† 1	11/171 (6.43%)	59	18/166 (10.84%)	136
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	36/171 (21.05%)	214	24/166 (14.46%)	235
Dysphonia ^† 1	4/171 (2.34%)	17	16/166 (9.64%)	109
Dyspnoea ^† 1	38/171 (22.22%)	165	33/166 (19.88%)	255
Epistaxis ^† 1	17/171 (9.94%)	49	43/166 (25.90%)	174
Oropharyngeal pain ^† 1	8/171 (4.68%)	21	10/166 (6.02%)	19
Skin and subcutaneous tissue disorders
Alopecia ^† 1	14/171 (8.19%)	103	56/166 (33.73%)	441
Dry skin ^† 1	11/171 (6.43%)	112	3/166 (1.81%)	9
Rash ^† 1	21/171 (12.28%)	83	15/166 (9.04%)	65
Vascular disorders
Flushing ^† 1	9/171 (5.26%)	45	4/166 (2.41%)	13
Hypertension ^† 1	3/171 (1.75%)	12	26/166 (15.66%)	293
Hypotension ^† 1	12/171 (7.02%)	24	11/166 (6.63%)	30
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 15.1

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

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Name/Title:	Chief Medical Officer
Organization:	Eli Lilly and Company
Phone:	800-545-5979
EMail:	ClinicalTrials.gov@lilly.com

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

Zinner RG, Obasaju CK, Spigel DR, Weaver RW, Beck JT, Waterhouse DM, Modiano MR, Hrinczenko B, Nikolinakos PG, Liu J, Koustenis AG, Winfree KB, Melemed SA, Guba SC, Ortuzar WI, Desaiah D, Treat JA, Govindan R, Ross HJ. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2015 Jan;10(1):134-42. doi: 10.1097/JTO.0000000000000366.

Layout table for additonal information

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00948675
Other Study ID Numbers:	13258 H3E-US-S130 ( Other Identifier: Eli Lilly and Company )
First Submitted:	July 28, 2009
First Posted:	July 29, 2009
Results First Submitted:	January 14, 2014
Results First Posted:	April 2, 2014
Last Update Posted:	October 29, 2021

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