This double-blind, placebo-controlled study will evaluate the benefit of first-line maintenance erlotinib (Tarceva) versus erlotinib at the time of disease progression in participants with advanced NSCLC who have not progressed following 4 cycles of platinum based-chemotherapy and whose tumor does not harbor an epidermal growth factor receptor (EGFR)-activating mutation. Participants will be randomized to receive either erlotinib 150 milligrams (mg) orally (PO) once daily or placebo. Participants who progress on placebo will receive erlotinib 150 mg PO once daily as second-line therapy, and those who progress on erlotinib may switch to a non-investigational, second-line chemotherapy. Treatments will continue until disease progression, death, or unacceptable toxicity. Participants may also be entered into a final Survival Follow-Up (SFU) period upon treatment discontinuation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
643
Placebo will be administered PO once daily as first-line maintenance until disease progression, death, or unacceptable toxicity.
Erlotinib will be administered as 150 mg PO once daily until disease progression, death, or unacceptable toxicity, as first-line maintenance or as second-line therapy for those who progress while receiving placebo.
Participants who progress on first-line maintenance erlotinib may receive an approved second-line therapy (but not EGFR targeted therapies) until disease progression, death, or unacceptable toxicity. The selected chemotherapy will be non-investigational and chosen at the discretion of the Investigator.
Unnamed facility
Gilroy, California, United States
Unnamed facility
Washington D.C., District of Columbia, United States
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Kansas City, Missouri, United States
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Missoula, Montana, United States
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Lebanon, New Hampshire, United States
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Percentage of Participants Who Died During the Overall Study
Participants were followed for survival until death or premature withdrawal. The percentage of participants who died during the Overall Study (BP, OLP, or SFU) was calculated.
Time frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death)
Overall Survival (OS) as Median Time to Event During the Overall Study
Participants were followed for survival until death or premature withdrawal. OS was defined as the interval between date of randomization and date of death from any cause. Median time to event during the Overall Study (BP, OLP, or SFU) was estimated using the Kaplan-Meier method and expressed in months.
Time frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death)
Percentage of Participants Event-Free (Alive) at 1 Year During the Overall Study
Participants were followed for survival until death or premature withdrawal. The percentage of participants event-free (i.e., still alive) at 1 year during the Overall Study was calculated.
Time frame: At 1 year
Percentage of Participants Who Died or Experienced Disease Progression During Blinded Treatment
Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Disease progression was defined as a greater than or equal to (≥) 20 percent (%) and ≥5-millimeter (mm) increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants who died or experienced disease progression during the BP was calculated.
Time frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)
Progression-Free Survival (PFS) as Median Time to Event During Blinded Treatment
Tumor response was evaluated using RECIST version 1.1. Disease progression was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. PFS was defined as the interval between date of randomization and date of first documented death or disease progression. Median time to event during the BP was estimated using the Kaplan-Meier method and expressed in weeks.
Time frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)
Percentage of Participants Event-Free (Alive and No Disease Progression) at 6 Months During Blinded Treatment
Tumor response was evaluated using RECIST version 1.1. Disease progression was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants event-free (i.e., still alive and without disease progression) at 6 months during the BP was calculated.
Time frame: At 6 months
Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to RECIST During Blinded Treatment
Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to less than (\<) 10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. The percentage of participants with a best overall response of either CR or PR (i.e., the objective response rate \[ORR\]) during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.
Time frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)
Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment
Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to \<10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. Stable disease (SD) was defined as neither sufficient shrinkage in target lesions to qualify for PR nor sufficient growth to qualify for disease progression. Disease progression (progressive disease/PD) was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants with each level of best tumor response during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.
Time frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)
Percentage of Participants With CR, PR, or SD According to RECIST During Blinded Treatment
Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to \<10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. SD was defined as neither sufficient shrinkage in target lesions to qualify for PR nor sufficient growth to qualify for disease progression. The percentage of participants with a best overall response of CR, PR, or SD (i.e., the disease control rate \[DCR\]) during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.
Time frame: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)
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Dayton, Ohio, United States
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Chattanooga, Tennessee, United States
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Spokane, Washington, United States
Unnamed facility
Tacoma, Washington, United States
Unnamed facility
Belo Horizonte, Minas Gerais, Brazil
...and 145 more locations