RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether erlotinib is more effective than a placebo in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying erlotinib to see how well it works compared to a placebo in treating patients with stage III or stage IV non-small cell lung cancer.

OBJECTIVES:

Primary

• Compare survival of patients with stage IIIB or IV non-small cell lung cancer that is not suitable for first-line chemotherapy treated with erlotinib vs placebo.

Secondary

• Compare progression-free survival and response rate.
• Compare toxicity.
• Compare the quality of life.
• Compare cost-effectiveness.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral erlotinib once daily for up to 24 months.
• Arm II: Patients receive oral placebo once daily for up to 24 months. Quality of life is assessed periodically.

After completion of study treatment, patients are followed periodically for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 664 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer

  • Advanced disease (stage IIIB or IV)
  • Diagnosis within 62 days prior to randomization

• Not suitable for first-line chemotherapy, as defined by the following criteria*:

  • ECOG performance status 2-3
  • ECOG performance status 0-1 AND creatinine clearance < 60 mL/min

• NOTE: *These criteria do not imply that all such patients are unsuitable for chemotherapy; patients are considered unsuitable on a case by case basis

• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

• Estimated life expectancy of at least 8 weeks
• Able to take oral medication
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No severe uncontrolled infection
• No unstable angina
• No myocardial infarction within the past month
• No uncontrolled inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)
• No acute renal failure
• Bilirubin < 2 times upper limit of normal (ULN)
• Transaminases < 2 times ULN (5 times ULN if liver metastases are present)
• Creatinine < 5 times ULN
• No evidence of other significant laboratory finding or uncontrolled medical illness that would interfere with study treatment or results comparison or render the patient at high risk from treatment complications
• No other prior or current malignant disease likely to interfere with study treatment or comparisons

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy

• No prior biological anticancer therapy (e.g., gefitinib, thalidomide, or cetuximab)

• No prior palliative radiotherapy

  • Prior palliative radiotherapy to bone metastases allowed within the past 2 weeks

• No concurrent cyclooxygenase-2 inhibitors