Trial Outcomes & Findings for Docetaxel or Pemetrexed With or Without Cetuximab in Patients With Recurrent or Progressive Non-Small Cell Lung Cancer (NCT NCT00095199)

Last Updated: 2012-10-15

Results Overview

PFS was defined as the time from randomization until the date of progressive disease (PD) or death from any cause. Participants who were alive and without progression were censored at the date of their last tumor assessment. PFS was assessed by the independent review committee (IRC) in the Pemetrexed group (Cetuximab \& Pemetrexed versus Pemetrexed) and by the investigator in the Docetaxel group (Cetuximab \& Docetaxel versus Docetaxel).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

939 participants

Primary outcome timeframe

Randomization to progression of disease or death due to any cause up to 59.6 months

Results posted on

2012-10-15

Participant Flow

Although 939 participants were initially randomized, 1 participant's data was inadvertently lost by a site prior to being entered into the database. As a result, we are reporting 938 as randomized.

Participant milestones

Participant milestones
Measure	Cetuximab & Pemetrexed Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles, until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 week cycle for up to six (3-week) cycles.	Cetuximab and Docetaxel Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.
Overall Study STARTED	302	304	167	166
Overall Study COMPLETED	6	62	7	23
Overall Study NOT COMPLETED	296	242	160	143

Reasons for withdrawal

Reasons for withdrawal
Measure	Cetuximab & Pemetrexed Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles, until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 week cycle for up to six (3-week) cycles.	Cetuximab and Docetaxel Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.
Overall Study Adverse Event	40	22	26	11
Overall Study Progressive disease	213	179	105	98
Overall Study Death	10	6	11	9
Overall Study Withdrawal by Subject	21	16	13	22
Overall Study Protocol Violation	4	4	2	0
Overall Study Liver function test results elevated	0	0	1	1
Overall Study Surgery needed could not start in 7 days	0	0	1	0
Overall Study Physician Decision	5	6	1	1
Overall Study Not eligible	1	7	0	1
Overall Study Started Palliative Radiotherapy	1	0	0	0
Overall Study Started radiotherapy regimen	0	1	0	0
Overall Study Primary tumor removed in other surgery	0	1	0	0
Overall Study Data inadvertently lost by site	1	0	0	0

Baseline Characteristics

Docetaxel or Pemetrexed With or Without Cetuximab in Patients With Recurrent or Progressive Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cetuximab & Pemetrexed n=301 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=304 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Cetuximab & Docetaxel n=167 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=166 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Total n=938 Participants Total of all reporting groups
Age Continuous	62.8 years STANDARD_DEVIATION 10.0 • n=5 Participants	64.0 years STANDARD_DEVIATION 9.4 • n=7 Participants	63.6 years STANDARD_DEVIATION 9.4 • n=5 Participants	63.9 years STANDARD_DEVIATION 9.2 • n=4 Participants	63.5 years STANDARD_DEVIATION 9.5 • n=21 Participants
Sex: Female, Male Female	128 Participants n=5 Participants	116 Participants n=7 Participants	75 Participants n=5 Participants	73 Participants n=4 Participants	392 Participants n=21 Participants
Sex: Female, Male Male	173 Participants n=5 Participants	188 Participants n=7 Participants	92 Participants n=5 Participants	93 Participants n=4 Participants	546 Participants n=21 Participants
Race/Ethnicity, Customized White	268 participants n=5 Participants	265 participants n=7 Participants	146 participants n=5 Participants	141 participants n=4 Participants	820 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	25 participants n=5 Participants	24 participants n=7 Participants	13 participants n=5 Participants	20 participants n=4 Participants	82 participants n=21 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	2 participants n=4 Participants	16 participants n=21 Participants
Race/Ethnicity, Customized Hispanic	4 participants n=5 Participants	8 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	16 participants n=21 Participants
Race/Ethnicity, Customized Unknown or Not Reported	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants
Region of Enrollment United States	265 participants n=5 Participants	270 participants n=7 Participants	152 participants n=5 Participants	151 participants n=4 Participants	838 participants n=21 Participants
Region of Enrollment Canada	36 participants n=5 Participants	34 participants n=7 Participants	15 participants n=5 Participants	15 participants n=4 Participants	100 participants n=21 Participants
Epidermal growth factor receptor (EGFR) by immunohistochemistry +1	36 participants n=5 Participants	35 participants n=7 Participants	13 participants n=5 Participants	19 participants n=4 Participants	103 participants n=21 Participants
Epidermal growth factor receptor (EGFR) by immunohistochemistry +2	46 participants n=5 Participants	53 participants n=7 Participants	26 participants n=5 Participants	34 participants n=4 Participants	159 participants n=21 Participants
Epidermal growth factor receptor (EGFR) by immunohistochemistry +3	118 participants n=5 Participants	108 participants n=7 Participants	72 participants n=5 Participants	58 participants n=4 Participants	356 participants n=21 Participants
Epidermal growth factor receptor (EGFR) by immunohistochemistry 0	21 participants n=5 Participants	32 participants n=7 Participants	12 participants n=5 Participants	10 participants n=4 Participants	75 participants n=21 Participants
Epidermal growth factor receptor (EGFR) by immunohistochemistry Missing	80 participants n=5 Participants	76 participants n=7 Participants	44 participants n=5 Participants	45 participants n=4 Participants	245 participants n=21 Participants
Karnofsky Performance Status 60	12 participants n=5 Participants	14 participants n=7 Participants	2 participants n=5 Participants	11 participants n=4 Participants	39 participants n=21 Participants
Karnofsky Performance Status 70	35 participants n=5 Participants	35 participants n=7 Participants	21 participants n=5 Participants	14 participants n=4 Participants	105 participants n=21 Participants
Karnofsky Performance Status 80	103 participants n=5 Participants	91 participants n=7 Participants	55 participants n=5 Participants	57 participants n=4 Participants	306 participants n=21 Participants
Karnofsky Performance Status 90	101 participants n=5 Participants	116 participants n=7 Participants	74 participants n=5 Participants	64 participants n=4 Participants	355 participants n=21 Participants
Karnofsky Performance Status 100	48 participants n=5 Participants	47 participants n=7 Participants	14 participants n=5 Participants	18 participants n=4 Participants	127 participants n=21 Participants
Karnofsky Performance Status Missing/unknown	2 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants	6 participants n=21 Participants
Pathological Diagnosis Adenocarcinoma	161 participants n=5 Participants	185 participants n=7 Participants	99 participants n=5 Participants	83 participants n=4 Participants	528 participants n=21 Participants
Pathological Diagnosis Large cell carcinoma	19 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	3 participants n=4 Participants	36 participants n=21 Participants
Pathological Diagnosis All other non-squamous diagnoses	45 participants n=5 Participants	41 participants n=7 Participants	20 participants n=5 Participants	29 participants n=4 Participants	135 participants n=21 Participants
Pathological Diagnosis Squamous cell carcinoma	76 participants n=5 Participants	71 participants n=7 Participants	41 participants n=5 Participants	51 participants n=4 Participants	239 participants n=21 Participants

PRIMARY outcome

Timeframe: Randomization to progression of disease or death due to any cause up to 59.6 months

Population: The intent-to-treat population (ITT) included all participants classified according to the treatment arms into which they were randomized, regardless of the actual treatment received. Censored participants: 10 in Cetuximab + Pemetrexed arm; 25 in Pemetrexed arm; 6 in Cetuximab + Docetaxel arm; 16 in Docetaxel arm.

Outcome measures

Outcome measures
Measure	Cetuximab & Docetaxel n=167 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously every 3 weeks cycle for up to six (3-week) cycles, after 6 cycles participants on the chemotherapy/cetuximab combination may continue cetuximab alone. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=166 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Cetuximab & Pemetrexed n=301 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=304 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.
Progression Free Survival (PFS)	2.37 months Interval 1.61 to 2.89	1.54 months Interval 1.45 to 2.5	2.89 months Interval 2.69 to 3.22	2.76 months Interval 2.53 to 3.29

SECONDARY outcome

Timeframe: Randomization to the date of death from any cause up to 72.8 months

Population: The intent-to-treat population (ITT) included all participants classified according to the treatment arms into which they were randomized, regardless of the actual treatment received. Censored participants: 24 in Cetuximab + Pemetrexed arm; 43 in Pemetrexed arm; 12 in Cetuximab + Docetaxel arm; 22 in Docetaxel arm.

OS was defined as the time from randomization to death. Participants without a date of death were censored on the last date participants were known to be alive, or lost to follow-up.

Outcome measures

Outcome measures
Measure	Cetuximab & Docetaxel n=167 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously every 3 weeks cycle for up to six (3-week) cycles, after 6 cycles participants on the chemotherapy/cetuximab combination may continue cetuximab alone. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=166 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Cetuximab & Pemetrexed n=301 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=304 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.
Overall Survival (OS)	5.75 months Interval 4.73 to 8.31	8.15 months Interval 6.11 to 9.2	6.93 months Interval 6.28 to 7.85	7.79 months Interval 6.77 to 8.41

SECONDARY outcome

Timeframe: Randomization until progression of disease or death from any cause up to 59.6 months

Population: The intent-to-treat population (ITT) included all participants classified according to the treatment arms into which they were randomized, regardless of the actual treatment received.

The best overall response rate (ORR) was the proportion of randomized participants with a best OR of CR or PR, according to modified World Health Organization (WHO) guidelines. It was calculated as the total number of participants with CR or PR divided by the total number of participants treated in that arm. Participants with no post-baseline evaluation were considered as non-responders. The tumor response was assessed by the independent review committee (IRC) in the Pemetrexed group and by the investigator in the Docetaxel group.

Outcome measures

Outcome measures
Measure	Cetuximab & Docetaxel n=167 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously every 3 weeks cycle for up to six (3-week) cycles, after 6 cycles participants on the chemotherapy/cetuximab combination may continue cetuximab alone. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=166 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Cetuximab & Pemetrexed n=301 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=304 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.
Proportion of Randomized Participants With the Best Overall Response (OR) of Partial Response (PR) or Complete Response (CR) (Overall Response Rate [ORR])	0.078 proportion of participants Interval 0.037 to 0.118	0.066 proportion of participants Interval 0.028 to 0.104	0.066 proportion of participants Interval 0.038 to 0.095	0.043 proportion of participants Interval 0.02 to 0.066

SECONDARY outcome

Timeframe: Randomization to progression of disease or death due to any cause up to 59.6 months

Population: The intent-to-treat population (ITT) included all participants classified according to the treatment arms into which they were randomized, regardless of the actual treatment received.

The disease control rate (DCR) was the proportion of randomized participants with a best OR of CR, PR or SD according to modified World Health Organization (WHO) guidelines. It was calculated as the total number of participants with CR, PR or SD divided by the total number of participants randomized in that arm. The tumor response was assessed by the independent review committee (IRC) in the Pemetrexed group and by the investigator in the Docetaxel group.

Outcome measures

Outcome measures
Measure	Cetuximab & Docetaxel n=167 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously every 3 weeks cycle for up to six (3-week) cycles, after 6 cycles participants on the chemotherapy/cetuximab combination may continue cetuximab alone. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=166 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Cetuximab & Pemetrexed n=301 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=304 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.
Proportion of Randomized Participants With Best Overall Response (OR) of Partial Response (PR), Complete Response (CR), or Stable Disease (SD)	0.335 proportion of participants Interval 0.264 to 0.407	0.253 proportion of participants Interval 0.187 to 0.319	0.522 proportion of participants Interval 0.465 to 0.578	0.480 proportion of participants Interval 0.424 to 0.536

SECONDARY outcome

Timeframe: At baseline, every 3 weeks and 30 days after end of therapy up to 50 months

Population: The randomized participants with baseline LCS scores less than or equal to 26.

The FACT-LCS is a set of 7 questions to inventory problems specific to lung cancer symptoms. Participants rate each item on a 5-point Likert-type scale from 0 (not at all) to 4 (very much). Scores range from 0-28 and higher score indicates fewer symptoms. Symptom response (improvement) was defined as ≥2 point increase from baseline in the 7-item LCS score that was maintained for 2 consecutive assessments at least 3 weeks, and not \>5 weeks apart for participants, whose baseline LCS score was ≤26. Symptom response rate was the percentage of participants with symptomatic response.

Outcome measures

Outcome measures
Measure	Cetuximab & Docetaxel n=150 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously every 3 weeks cycle for up to six (3-week) cycles, after 6 cycles participants on the chemotherapy/cetuximab combination may continue cetuximab alone. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=155 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Cetuximab & Pemetrexed n=280 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=280 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.
Percentage of Participants With Symptomatic Response (Symptom Response Rates) Using the Lung Cancer Subscale (LCS) Scores of Functional Assessment of Cancer Therapy for Participants With Lung Cancer (FACT-L)	17.3 percentage of participants Interval 11.3 to 23.4	13.5 percentage of participants Interval 8.2 to 18.9	17.1 percentage of participants Interval 12.7 to 21.6	22.9 percentage of participants Interval 17.9 to 27.8

SECONDARY outcome

Timeframe: Randomization until symptomatic progression up to 48.3 months

Population: All randomized participants with a baseline LCS \>= 2 were included. Censored participants: 237 in Cetuximab plus Pemetrexed arm; 244 in Pemetrexed arm; 126 in Cetuximab plus Docetaxel arm; 131 in Docetaxel arm.

The FACT-LCS (see description in Outcome measure 5) inventories problems specific to lung cancer symptoms. Using this Scale, Symptom progression = a ≥ 2 point decrease from baseline in LCS score maintained for 2 consecutive assessments ≥3 weeks, and \<5 weeks, apart. The symptom progression date = the first of 2 consecutive assessments with a ≥2 point decline. Time to symptomatic progression = the time from randomization to the symptom progression date. For participants with no symptom progression, time to symptomatic progression was censored the date of last symptom assessment.

Outcome measures

Outcome measures
Measure	Cetuximab & Docetaxel n=152 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously every 3 weeks cycle for up to six (3-week) cycles, after 6 cycles participants on the chemotherapy/cetuximab combination may continue cetuximab alone. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=158 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Cetuximab & Pemetrexed n=289 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=287 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.
Time to Symptomatic Progression	NA months Interval 7.0 to The median time to symptomatic progression is not estimable because the probability of symptomatic progression free never decreased to 0.5	NA months The median time to symptomatic progression is not estimable because the probability of symptomatic progression free never decreased to 0.5	NA months The median time to symptomatic progression is not estimable because the probability of symptomatic progression free never decreased to 0.5	NA months The median time to symptomatic progression is not estimable because the probability of symptomatic progression free never decreased to 0.5

SECONDARY outcome

Timeframe: Time of first occurrence of either (PR) or (CR) to the first date of progressive disease or death up to 32.5 months

Population: All randomized participants with a best overall response of CR or PR. Censored participants: 1 in Cetuximab plus Pemetrexed arm; 2 in Pemetrexed arm; 1 in Cetuximab plus Docetaxel arm; 0 in Docetaxel arm.

The duration of response, in participants with best OR of complete response (CR) or partial response (PR), was measured from the date criteria are met for CR/PR (not confirmation date, whichever was first recorded), until the first occurrence date that the criteria of progressive disease (PD) was met, or death. Participants who were alive and without progression were censored at the date of their last independent review committee (IRC) tumor assessment. The tumor response and progression were assessed by the IRC in the Pemetrexed group and by the investigator in the Docetaxel group.

Outcome measures

Outcome measures
Measure	Cetuximab & Docetaxel n=13 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously every 3 weeks cycle for up to six (3-week) cycles, after 6 cycles participants on the chemotherapy/cetuximab combination may continue cetuximab alone. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=11 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Cetuximab & Pemetrexed n=20 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=13 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.
Duration of Overall Response (OR)	5.36 months Interval 2.73 to 6.93	5.39 months Interval 3.12 to 7.16	4.17 months Interval 2.92 to 5.45	6.93 months Interval 3.98 to 16.36

SECONDARY outcome

Timeframe: Time from first dose to 30 days after last dose of study therapy up to 28.3 months for Cetuximab & Pemetrexed (versus Pemetrexed alone) and up to 54.3 months for Cetuximab + Docetaxel (versus Docetaxel alone)

Population: All randomized participants receiving at least 1 dose of study drug made up the safety population for this outcome measure. Investigators graded events using CTCAE v3.0. Mapping of investigator verbatim terms for toxicity to CTCAE terms was done by the sponsor/designee using CTCAE v4.0.

National Cancer Institutes-Common Toxicity Criteria version 3.0 was used by investigators to assess participant toxicities. Mapping of investigator verbatim terms to CTCAE terms was done by the sponsor/designee using CTCAE v4.0. Participants reported had grade 3 or 4 toxicities (or both potentially). Grade 3 AEs: severe or medically significant but not immediately life-threatening;hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 AEs: life-threatening consequences; urgent intervention indicated.

Outcome measures

Outcome measures
Measure	Cetuximab & Docetaxel n=159 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously every 3 weeks cycle for up to six (3-week) cycles, after 6 cycles participants on the chemotherapy/cetuximab combination may continue cetuximab alone. Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Docetaxel n=149 Participants Docetaxel 75 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.	Cetuximab & Pemetrexed n=292 Participants Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.	Pemetrexed n=289 Participants Pemetrexed 500 mg/m\^2 administered intravenously on Day 1 of 3 weeks cycle for up to six (3-week) cycles.
Number of Participants With Common Toxicity Criteria (CTC) Grade 3 or 4 Toxicities	112 participants	97 participants	179 participants	143 participants

Adverse Events

Cetuximab & Pemetrexed

Serious events: 119 serious events

Other events: 289 other events

Deaths: 0 deaths

Pemetrexed

Serious events: 86 serious events

Other events: 281 other events

Deaths: 0 deaths

Cetuximab and Docetaxel

Serious events: 84 serious events

Other events: 159 other events

Deaths: 0 deaths

Docetaxel

Serious events: 60 serious events

Other events: 147 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60