Trial Outcomes & Findings for A Study of Tarceva (Erlotinib) and Standard of Care Chemotherapy in Patients With Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer (NSCLC) (NCT NCT00556322)

NCT ID: NCT00556322

Last Updated: 2015-02-23

Results Overview

Overall survival (OS) was determined from the date of randomization to the date of death irrespective of the cause of death.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 424 participants
• Primary outcome timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 or Death and Every 12 Weeks until Death or Data Cut off (07 September 2010) up to 52 months
• Results posted on: 2015-02-23

Participant Flow

Participant milestones

Measure	Comparator Participants received either pemetrexed 500 milligrams per square meter (mg/m\^2) every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Overall Study STARTED	221	203
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	221	203

Reasons for withdrawal

Measure	Comparator Participants received either pemetrexed 500 milligrams per square meter (mg/m\^2) every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Overall Study Insufficient therapeutic response	158	168
Overall Study Adverse Event	7	4
Overall Study Other	4	1
Overall Study Lost to Follow-up	5	3
Overall Study Withdrawal by Subject	19	7
Overall Study Protocol Violation	5	1
Overall Study Ongoing at data cutoff	3	5
Overall Study Death	20	14

Baseline Characteristics

A Study of Tarceva (Erlotinib) and Standard of Care Chemotherapy in Patients With Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.	Total n=424 Participants Total of all reporting groups
Age, Continuous	58.3 years STANDARD_DEVIATION 9.90 • n=5 Participants	58.6 years STANDARD_DEVIATION 9.64 • n=7 Participants	58.4 years STANDARD_DEVIATION 9.76 • n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	42 Participants n=7 Participants	103 Participants n=5 Participants
Sex: Female, Male Male	160 Participants n=5 Participants	161 Participants n=7 Participants	321 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 or Death and Every 12 Weeks until Death or Data Cut off (07 September 2010) up to 52 months

Population: FAS population

Overall survival (OS) was determined from the date of randomization to the date of death irrespective of the cause of death.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Percentage of Participants Who Died (All Participants; Data Cutoff: 07 September 2010)	81.0 percentage of participants	77.8 percentage of participants

PRIMARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months

Population: FAS population

OS was determined from the date of randomization to the date of death irrespective of the cause of death. Kaplan-Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Duration of Overall Survival in All Participants (Data Cutoff 07 September 2010)	5.5 months Interval 4.4 to 7.1	5.3 months Interval 4.0 to 6.0

PRIMARY outcome

Timeframe: 1 Year

Population: FAS population

OS was determined from the date of randomization to the date of death irrespective of the cause of death. Kaplan-Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Probable Percentage of Participants Remaining Alive at 1 Year	24.0 percentage of participants Interval 18.0 to 30.0	26.0 percentage of participants Interval 19.0 to 32.0

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months

Population: FAS population; Only participants with confirmed presence or absence of EGFR were included in the analysis. number (n) equals (=) number of participants who were EGFR positive or negative

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by immunohistochemistry (IHC). OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=188 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=175 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Percentage of Participants Who Died in Epidermal Growth Factor Receptor (EGFR) Positive and Negative Population EGFR Positive (n=149,143)	79.9 percentage of participants	76.9 percentage of participants
Percentage of Participants Who Died in Epidermal Growth Factor Receptor (EGFR) Positive and Negative Population EGFR Negative (n=39,32)	79.5 percentage of participants	75.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months

Population: FAS population; Only participants with confirmed presence or absence of EGFR were included in the analysis. n=number of participants who were EGFR positive or negative

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=188 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=175 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Duration of OS in EGFR Positive and Negative Population EGFR Positive (n=149,143)	5.5 months Interval 4.1 to 7.5	5.6 months Interval 4.0 to 7.6
Duration of OS in EGFR Positive and Negative Population EGFR Negative (n=39,32)	6.7 months Interval 3.1 to 11.5	5.4 months Interval 3.7 to 7.8

SECONDARY outcome

Timeframe: 1 Year

Population: FAS population; n=number of EGFR positive or negative participants remaining at risk

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Probable Percentage of Participants Remaining Alive at 1 Year in the EGFR Positive and Negative Population EGFR Positive (n=30,32)	27.0 percentage of participants Interval 19.0 to 34.0	30.0 percentage of participants Interval 22.0 to 38.0
Probable Percentage of Participants Remaining Alive at 1 Year in the EGFR Positive and Negative Population EGFR Negative (n=8,4)	28.0 percentage of participants Interval 12.0 to 43.0	20.0 percentage of participants Interval 4.0 to 36.0

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months

Population: FAS population

Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.0). Progressive Disease was defined as at least a 20 percent (%) increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The primary analysis of PFS used objective progression (RECIST) plus clinical progression (based on relevant clinical findings - if any). A further assessment of PFS was made on objective (radiological) progression. If clinical progression was diagnosed first, the participant was censored at the date of the last tumor assessment, where non-progression was documented.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Percentage of Participants With Disease Progression or Death (All Participants; Data Cut Off 07 September 2010)	83.3 percentage of participants	92.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months

Population: FAS population

Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Progression-Free Survival (PFS) in All Participants (Data Cutoff 07 September 2010)	8.6 weeks Interval 7.1 to 12.1	6.3 weeks Interval 6.1 to 6.9

SECONDARY outcome

Timeframe: 6 Months

Population: FAS population

Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Event free estimates were determined using Kaplan-Meier estimates.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months	17.0 percentage of participants Interval 12.0 to 22.0	13.0 percentage of participants Interval 8.0 to 18.0

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months

Population: FAS population; Only participants with confirmed presence or absence of EGFR were included in the analysis. n=number of participants who were EGFR positive or negative

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC.Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as At least a 20 % increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Measure	Comparator n=188 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=175 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Percentage of Participants With Disease Progression or Death in EGFR Positive and Negative Population (Data Cut Off 07 September 2010) EGFR Positive (n=149,143)	79.9 percentage of participants	93.7 percentage of participants
Percentage of Participants With Disease Progression or Death in EGFR Positive and Negative Population (Data Cut Off 07 September 2010) EGFR Negative (n=39,32)	89.7 percentage of participants	90.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months

Population: FAS population; Only Participants with confirmed status of EGFR were included in the analysis; number of participants who were EGFR positive or negative

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first in EGFR positive and negative populations. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Kaplan-Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=188 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=175 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
PFS in EGFR Positive and Negative Population (Data Cutoff 07 September 2010) EGFR Positive (n=149,143)	8.9 weeks Interval 7.1 to 12.6	6.3 weeks Interval 6.1 to 7.3
PFS in EGFR Positive and Negative Population (Data Cutoff 07 September 2010) EGFR Negative (n=39,32)	11.5 weeks Interval 6.7 to 14.7	6.7 weeks Interval 5.9 to 12.0

SECONDARY outcome

Timeframe: 6 Months

Population: FAS population; n=number of EGFR positive or negative participants who remained at risk

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. Tumor response was evaluated according to RECIST criteria (version 1.0). PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first in EGFR positive and negative populations. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Event free estimates were determined using Kaplan-Meier estimates.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months in EGFR Positive and Negative Population EGFR Positive (n=23,18)	20.0 percentage of participants Interval 13.0 to 28.0	13.0 percentage of participants Interval 7.0 to 19.0
Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months in EGFR Positive and Negative Population EGFR Negative (n=4,5)	11.0 percentage of participants Interval 1.0 to 21.0	16.0 percentage of participants Interval 3.0 to 29.0

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Death or up to 52 months

Population: FAS population

Best overall response was defined as the best response according to RECIST recorded from the date of randomization until disease progression or recurrence. CR: disappearance of all target lesions; PR: reduction by at least 30% of the sum of the longest diameters of each target lesion, taking the initial sum of the longest diameters as a reference; Stable disease (SD): insufficient tumor reduction to define partial response and/or tumor increase less than that necessary to define tumor progression, taking as a reference the smallest sum of the longest diameter since the start of treatment; Progressive Disease (PD): increase by at least 20% in the sum of LD of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. 95% Confidence Interval (CI) for one sample binomial using Pearson-Clopper method. Participants with a missing response were considered non-responders.

Outcome measures

Measure	Comparator n=221 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=203 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator Using RECIST	6.3 percentage of participants Interval 3.5 to 10.4	7.9 percentage of participants Interval 4.6 to 12.5

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the Functional Assessment of Cancer Treatment-General scale (FACT-G) and the lung cancer subscale (LCS). The FACT-L total score ranges from 0 to 136, higher scores represent better QOL.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=157 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Percentage of Participants With Deterioration in Quality of Life Determined Using Functional Assessment of Cancer Therapy - Lung (FACT-L)	66.1 percentage of participants	66.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the FACT-G and the LCS. The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Time to deterioration of QoL or symptom progression is defined as time from randomization until either a clinically meaningful decline from baseline in Total FACT-L or, death on study, whichever occurs first. The clinically meaningful decline that was used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment. Kaplan-Meier estimate was used to determine time to event.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=157 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Time to Deterioration in Quality of Life Using FACT-L	9.0 weeks Interval 7.1 to 11.6	6.3 weeks Interval 6.1 to 8.0

SECONDARY outcome

Timeframe: 6 Months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the FACT-G and the LCS. The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Kaplan Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=157 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Probable Percentage of Participants Remaining Without Deterioration in Quality of Life at 6 Months as Assessed by FACT-L	25.0 percentage of participants Interval 17.0 to 34.0	19.0 percentage of participants Interval 11.0 to 26.0

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

Participants' responses on the FACT-L were scored according to the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=158 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Percentage of Participants With Symptomatic Progression Using FACT-L	60.6 percentage of participants	62.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

Participants' responses on the FACT-L were scored according to FACIT measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline. Kaplan Meier estimated were used for analysis.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=158 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Time to Symptomatic Progression Using FACT-L	9.0 weeks Interval 7.0 to 12.1	7.1 weeks Interval 6.1 to 9.3

SECONDARY outcome

Timeframe: 6 Months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

Participants' responses on the FACT-L were scored according to FACIT measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline. Kaplan Meier estimated were used for analysis.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=158 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Probable Percentage of Participants With Symptomatic Progression at 6 Months as Assessed by FACT-L	27 percentage of participants Interval 18.0 to 36.0	27 percentage of participants Interval 18.0 to 35.0

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

TOI is defined as the sum of the scores of the Physical Well- Being (PWB), Functional Well-Being (FWB), and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=158 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Percentage of Participants With Deterioration in the Trial Outcome Index (TOI)	60.0 percentage of participants	63.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

TOI is defined as the sum of the scores of the PW, FWB, and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6- point decline from baseline. Kaplan-Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=158 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Time to Deterioration in the TOI	9.3 weeks Interval 7.6 to 13.0	6.7 weeks Interval 6.1 to 9.4

SECONDARY outcome

Timeframe: 6 Months

Population: FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

TOI is defined as the sum of the scores of the PW, FWB, and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline. Kaplan-Meier estimates were used for analysis.

Outcome measures

Measure	Comparator n=165 Participants Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=158 Participants Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.
Probable Percentage of Participants With Deterioration in the TOI at 6 Months as Assessed by FACT-L	28 percentage of participants Interval 19.0 to 37.0	21 percentage of participants Interval 13.0 to 29.0

Adverse Events

Comparator

Serious events: 31 serious events

Other events: 106 other events

Deaths: 0 deaths

Erlotinib

Serious events: 20 serious events

Other events: 125 other events

Deaths: 0 deaths

Serious adverse events

Measure	Comparator n=213 participants at risk Participants received either Alimta 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or Taxotere 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, Taxotere was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=196 participants at risk Participants received a single oral dose of erlotinib 150 mg/day until disease progression, unacceptable toxicity or death.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Respiratory, thoracic and mediastinal disorders Pulmonary effusion	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Musculoskeletal and connective tissue disorders Back pain	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Abdominal pain	0.94% 2/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Constipation	0.94% 2/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Enterocolitis	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Gastric perforation	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Oesophagitis	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Proctitis	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Subileus	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Blood and lymphatic system disorders Anaemia	1.9% 4/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Blood and lymphatic system disorders Febrile neutropenia	0.94% 2/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Blood and lymphatic system disorders Neutropenia	0.94% 2/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Blood and lymphatic system disorders Pancytopenia	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Blood and lymphatic system disorders Thrombocytopenia	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Infections and infestations Pneumonia	1.4% 3/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Infections and infestations Erysipelas	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Infections and infestations Gastroenteritis	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Infections and infestations Lower respiratory tract infection	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Infections and infestations Pharyngitis bacterial	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
General disorders Death	0.94% 2/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
General disorders Chest pain	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
General disorders Pyrexia	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Vascular disorders Venous thrombosis limb	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Vascular disorders Deep vein thrombosis	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Vascular disorders Vena cava thrombosis	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Cardiac disorders Supraventricular tachycardia	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Cardiac disorders Cardiac failure	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Renal and urinary disorders Renal failure	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Injury, poisoning and procedural complications Narcotic intoxication	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Injury, poisoning and procedural complications Vascular access complication	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Nervous system disorders Cerebrovascular accident	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Nervous system disorders Ischaemic stroke	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Nervous system disorders Spinal cord compression	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	2.0% 4/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.94% 2/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.51% 1/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).

Other adverse events

Measure	Comparator n=213 participants at risk Participants received either Alimta 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or Taxotere 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, Taxotere was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.	Erlotinib n=196 participants at risk Participants received a single oral dose of erlotinib 150 mg/day until disease progression, unacceptable toxicity or death.
Skin and subcutaneous tissue disorders Rash	3.3% 7/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	37.8% 74/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Skin and subcutaneous tissue disorders Alopecia	11.7% 25/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	0.00% 0/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.47% 1/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	6.1% 12/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Skin and subcutaneous tissue disorders Acne	0.00% 0/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	5.6% 11/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Diarrhoea	5.6% 12/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	18.9% 37/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Gastrointestinal disorders Nausea	13.6% 29/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	7.7% 15/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
General disorders Asthenia	10.3% 22/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	6.6% 13/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
General disorders Fatigue	8.5% 18/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	4.6% 9/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
General disorders Pyrexia	6.6% 14/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	5.1% 10/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
General disorders Chest pain	2.8% 6/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	5.1% 10/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
General disorders Oedema peripheral	5.2% 11/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	1.5% 3/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.7% 25/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	10.2% 20/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Respiratory, thoracic and mediastinal disorders Cough	8.9% 19/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	7.7% 15/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Metabolism and nutrition disorders Decreased appetite	10.3% 22/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	8.7% 17/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).
Blood and lymphatic system disorders Anaemia	7.5% 16/213 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).	2.0% 4/196 • All adverse events (related and unrelated) occurring during the study and for up to 28 days after the last dose of study medication were reported. All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).

Additional Information

Medical Communications

Hoffmann- LaRoche

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Email: genentech@druginfo.com

Results disclosure agreements

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

Restriction type: OTHER