A Study of Tarceva (Erlotinib) Following Platinum-Based Chemotherapy in Patients With Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This 2 arm study will evaluate the efficacy, safety, and pharmacokinetics of Tarceva, compared with placebo, following platinum-based chemotherapy in patients with advanced, recurrent, or metastatic NSCLC who have not had disease progression or unacceptable toxicity during chemotherapy. Following 4 cycles of platinum-based chemotherapy, eligible patients will be randomized to receive either Tarceva 150mg po daily, or placebo daily. The anticipated time on study treatment is until disease progression; the target sample size is 500+ individuals.

Official Title
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A Randomized, Double-blind Study to Evaluate the Effect of Tarceva or Placebo Following Platinum-based CT on Overall Survival and Disease Progression in Patients With Advanced, Recurrent or Metastatic NSCLS Who Have Not Experienced Disease Progression or Unacceptable Toxicity During Chemotherapy

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: erlotinib [Tarceva]
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >=18 years of age; histologically documented, locally advanced , recurrent or metastatic NSCLC; measurable disease; no disease progression after 4 cycles of platinum-based chemotherapy. Exclusion Criteria: unstable systemic disease; any other malignancies in the last 5 years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib<br>Participants received erlotinib, 150 milligrams (mg), orally (PO), daily from randomization until progressive disease (PD), death, or unacceptable toxicity. | Drug: erlotinib [Tarceva]<br>* 150mg po daily<br>|
| Placebo Comparator: Placebo<br>Participants received a placebo, PO, daily, from randomization until PD, death, or unacceptable toxicity. | Drug: Placebo<br>* po daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With PD According to Response Evaluation Criteria in Solid Tumors (RECIST) or Death (Data Cutoff 17 May 2008) | Progression-free survival (PFS) was defined as the time from randomization to PD or death, whichever occurred first. For target lesions (TLs), PD was defined at least a 20 percent (%) increase in the sum of the largest diameter (SLD), taking as reference the smallest SLD recorded from baseline (BL) more the appearance of one or more new lesions. For non-target lesions (NTLs), PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. | Screening, BL [≤21 days after randomization], every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| PFS in All Participants (Data Cutoff 17 May 2008) | The median time, in weeks, from randomization to PFS event. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% confidence interval (CI) was estimated using Kaplan-Meier methodology. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Probable Percentage of Participants Remaining Alive and Free of Disease Progression at 6 Months (Data Cutoff 17 May 2008) | PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL more the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology. | 6 months | 
| Percentage of Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry (IHC) Positive Participants With PD or Death (Data Cutoff 17 May 2008) | PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| PFS in EGFR IHC Positive Population (Data Cutoff 17 May 2008) | The median time, in weeks, from randomization to PFS event. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology. | Screening, BL (≤ 21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Probable Percentage of Participants in the EGFR IHC Positive Population Remaining Alive and Progression Free at 6 Months (Data Cutoff 17 May 2008) | PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of All Participants Who Died (Data Cutoff 12 January 2012) |  | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 12 January 2012 (up to 71 months). | 
| Overall Survival (OS) in All Participants (Data Cutoff 12 January 2012) | OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology. | Screening, BL (≤ 21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 12 January 2012 (up to 71 months) | 
| Probable Percentage of Participants Remaining Alive at 1 Year (Data Cutoff 12 January 2012) | OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology. | 1 year | 
| Percentage of EGFR IHC Positive Participants Who Died (Data Cutoff 12 January 2012) |  | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 12 January 2012 (up to 71 months) | 
| OS in EGFR IHC Positive Population (Data Cutoff 12 January 2012) | OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 12 January 2012 (up to 71 months) | 
| Probable Percentage of Participants in the EGFR IHC Positive Population Remaining Alive at 1 Year (Data Cutoff 12 January 2012) | OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology. | 1 year | 
| Percentage of EGFR IHC Negative Participants With PD or Death (Data Cutoff 17 May 2008) | PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 71 months) | 
| PFS in EGFR IHC Negative Participants (Data Cutoff 17 May 2008) | The median time, in weeks, from randomization to PFS event. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Probable Percentage of Participants in the EGFR IHC Negative Population Remaining Alive and Free of Disease Progression at 6 Months (Data Cutoff 17 May 2008) | PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology. | 6 months | 
| Percentage of EGFR IHC Negative Participants Who Died (Data Cutoff 17 May 2008) |  | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| OS in EGFR IHC Negative Participants (Data Cutoff 17 May 2008) | OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Probable Percentage of Participants in the EGFR IHC Negative Population Remaining Alive at 1 Year (Data Cutoff 17 May 2008) | OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology. | 1 year | 
| Time to Progression (Data Cutoff 17 May 2008) | The median time, in weeks, between randomization and TTP event. Participants without PD were censored at the date of last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of PD, the participant was censored at the date of last tumor assessment before starting new chemotherapy. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Probable Percentage of Participants Remaining Progression-Free in the TTP Analysis at 6 Months (Data Cutoff 17 May 2008) | TTP was defined as the time from the date of randomization to the first date PD was recorded. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD were censored at the date of last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of PD, the participant was censored at the date of last tumor assessment before starting new chemotherapy. The 95% CI was estimated using Kaplan-Meier methodology. | 6 months | 
| Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST (Data Cutoff 17 May 2008) | BOR was defined as CR or PR confirmed by repeat assessments performed no less than 4 weeks after the criteria for response was first met. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline (BL) SLD. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% CI for one sample binomial was determined using the Pearson-Clopper method. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Percentage of Participants With a CR, PR, Stable Disease (SD), or PD According to RECIST (Data Cutoff 17 May 2008) | For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD/incomplete response was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. The 95% CI for one sample binomial was determined using the Pearson-Clopper method. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Percentage of Participants With a Response Upgrade From BL According to RECIST (Data Cutoff 17 May 2008) | Response upgrade was defined by a change of PR to CR or of SD to PR or CR from BL to the end of treatment. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD/incomplete response was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. The 95% CI for one sample binomial was determined using the Pearson-Clopper method. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Percentage of Participants With a Change of PR to CR or SD to PR or CR From BL to End of Treatment According to RECIST (Data Cutoff 17 May 2008) | For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD/incomplete response was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. The 95% CI for one sample binomial was determined using the Pearson-Clopper method. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Percentage of Participants With CR, PR, or SD or With SD [Maintained For Greater Than (>) 12 Weeks] or CR or PR (Data Cutoff 17 May 2008) | Disease control was defined as a best response of CR or PR or SD or a best response of SD for more than 12 weeks, or CR or PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD/incomplete response was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits. The 95% CI for one sample binomial was determined using the Pearson-Clopper method. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Percentage of Participants With Symptom Progression Assessed Using the Lung Cancer Subscale (LCS) (Data Cutoff 17 May 2008) | LCS scores were obtained from a 7-item questionnaire from the Functional Assessment of Cancer Therapy - Lung (FACT-L) version (V) 4. Participants responded to questions assessing symptoms commonly reported by lung cancer patients; such as shortness of breath, loss of weight, and tightness in chest; on a scale from 0-4, where 0 equaled (=) not at all and 4 = very much. The participants' responses were summed to result in an overall score, where a higher score indicated more severe symptoms. A change of 2 to 3 points in score was determined to be a clinically meaningful decline. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Time to Symptom Progression (Data Cutoff 17 May 2008) | The median time, in weeks, from the date of randomization to the date of documented clinically meaningful decline in LCS from BL or death, whichever occurred first. LCS scores were obtained from a 7-item questionnaire from the FACT-L V 4. Participants responded to questions assessing symptoms commonly reported by lung cancer patients; such as shortness of breath, loss of weight, and tightness in chest; on a scale from 0-4, where 0 = not at all and 4 = very much. The participants' responses were summed to result in an overall score, where a higher score indicated more severe symptoms. A change of 2 to 3 points in score was determined to be a clinically meaningful decline. The 95% CI was determined using Kaplan-Meier methodology. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Probable Percentage of Participants Remaining Without Symptom Progression at 6 Months (Data Cutoff 17 May 2008) | LCS scores were obtained from a 7-item questionnaire from the FACT-L V 4. Participants responded to questions assessing symptoms commonly reported by lung cancer patients; such as shortness of breath, loss of weight, and tightness in chest; on a scale from 0-4, where 0 = not at all and 4 = very much. The participants' responses were summed to result in an overall score, where a higher score indicated more severe symptoms. A change of 2 to 3 points in score was determined to be a clinically meaningful decline. The 95% CI was estimated using Kaplan-Meier methodology. | 6 months | 
| Percentage of Participants With Deterioration Assessed Using the Trial Outcome Index (Data Cutoff 17 May 2008) | The Trial Outcome Index (TOI) was defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = not at all and 4 = very much. Higher score indicated more severe symptoms. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L assessment. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Time to Deterioration in TOI (Data Cutoff 17 May 2008) | The median time, in weeks, from the date of randomization until a clinically meaningful decline from BL in TOI or death, whichever occurred first. TOI was defined as the sum of PWB, FWB, and LCS scores, which were obtained from 7-item questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = not at all and 4 = very much. Higher score indicated more severe symptoms. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from BL Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L assessment. The 95% CI was determined using Kaplan-Meier methodology. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Probable Percentage of Participants Remaining Without Deterioration in TOI at 6 Months (Data Cutoff 17 May 2008) | TOI was defined as the sum of the scores of the PWB, FWB, and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = not at all and 4 = very much. Higher score indicated more severe symptoms. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L assessment. The 95% CI was estimated using Kaplan-Meier methodology. | 6 months | 
| Percentage of Participants With Deterioration in Quality of Life Assessed Using TOI, SWB, and EWB (Data Cutoff 17 May 2008) | Deterioration in quality of life (QoL) was defined as a clinically meaningful decline in the total FACT-L score, the sum of the TOI, Social/Family Well-Being (SWB) and Emotional Well-Being (EWB) of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = not at all and 4 = very much. Higher score indicated more severe symptoms. A clinically meaningful decline in FACT-L score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Time to Deterioration in QoL (Data Cutoff 17 May 2008) | The median time, in weeks, from the date of randomization until a clinically meaningful decline from BL in total FACT-L or death, whichever occurred first. Total FACT-L score was defined as the sum of the TOI, SWB and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = not at all and 4 = very much. Higher score indicated more severe symptoms. A clinically meaningful decline in FACT-L score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L assessment. The 95% CI was determined using Kaplan-Meier methodology. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Probable Percentage of Participants Remaining Without Deterioration in QoL at 6 Months (Data Cutoff 17 May 2008) | Deterioration in QoL was defined as a clinically meaningful decline in the total FACT-L score, the sum of the TOI, SWB and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = not at all and 4 = very much. Higher score indicated more severe symptoms. A clinically meaningful decline in FACT-L score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L. The 95% CI was estimated using Kaplan-Meier methodology. | 6 months | 
| Functional Assessment of Chronic Illness Therapy - Lung (FACT-L) Scores (Data Cutoff 17 May 2008) | Total FACT-L score=sum of TOI, SWB, and EWB of FACT-L questionnaires. TOI (PWB+FWB+LCS), SWB, and EWB scores obtained from 7-item (6-item for EWB) questionnaires from FACT-L V4. Participants responded to questions assessing symptoms (scale 0-4; 0=not at all and 4=very much). Higher score=more severe symptoms. The 7-item LCS assessed symptoms such as shortness of breath, loss of weight, tightness in chest. Participants responded to questions assessing symptoms (scale: 0-4; 0=not at all and 4=very much). Scores from 0-35; higher score=more severe symptoms. The 27 items of FACT-G were scored in the following domains: PWB (7 items, total score 0-28), SWB (7 items; total score 0-28), EWB (6 items, total score 0-24), and FWB (7 items; total score 0-28), higher scores=better QoL. Participants responded to items on 5-point Likert scale (0=Not at all to 4=Very much; total score: 0-108). Higher score=better QOL. TOI score=PWB+FWB+LCS; Total TOI score: 0-92; higher scores=better QOL. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) | 
| Change From BL in FACT-L Scores (Data Cutoff 17 May 2008) | Total FACT-L score=sum of TOI, SWB, and EWB of FACT-L questionnaires. TOI (PWB+FWB+LCS), SWB, and EWB scores obtained from 7-item (6-item for EWB) questionnaires from FACT-L V4. Participants responded to questions assessing symptoms (scale 0-4; 0=not at all and 4=very much). Higher score=more severe symptoms. The 7-item LCS assessed symptoms such as shortness of breath, loss of weight, tightness in chest. Participants responded to questions assessing symptoms (scale: 0-4; 0=not at all and 4=very much). Scores from 0-35; higher score=more severe symptoms. The 27 items of FACT-G were scored in the following domains: PWB (7 items, total score 0-28), SWB (7 items; total score 0-28), EWB (6 items, total score 0-24), and FWB (7 items; total score 0-28), higher scores=better QoL. Participants responded to items on 5-point Likert scale (0=Not at all to 4=Very much; total score: 0-108). Higher score=better QOL. TOI score=PWB+FWB+LCS; Total TOI score: 0-92; higher scores=better QOL. | Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months) |