Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status

Abstract

Purpose: To compare gefitinib with placebo in chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status.

Patients and methods: NSCLC patients (chemotherapy naïve, WHO performance status 2 or 3; unfit for chemotherapy; stage IIIB/IV) were randomly assigned to gefitinib (250 mg/d) plus best supportive care (BSC; n = 100) or placebo plus BSC (n = 101). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and safety. Correlation of gefitinib efficacy with EGFR gene copy number (fluorescent in situ hybridization [FISH]) was explored.

Results: Hazard ratios (HRs; gefitinib:placebo) were 0.82 (95% CI, 0.60 to 1.12; P = .217) for PFS and 0.84 (95% CI, 0.62 to 1.15; P = .272) for OS. As expected for this patient population, OS for both arms was poor, at about 3 months. ORRs were 6.0% (gefitinib) and 1.0% (placebo). QOL and PSI rates were 21.1% and 28.3% (gefitinib) and 20.0% and 28.3% (placebo), respectively. In EGFR FISH-positive patients (n = 32), HRs were 0.29 (95% CI, 0.11 to 0.73) for PFS and 0.44 (95% CI, 0.17 to 1.12) for OS. No unexpected adverse events occurred.

Conclusion: There was no statistically significant difference in PFS, OS, and ORRs after treatment with gefitinib or placebo, in the overall population; improvements in QOL and symptoms were similar in both groups. Tolerability profile of gefitinib was consistent with previous studies. PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors.

Fig 1.

Patient disposition.

Fig 2.

Kaplan-Meier curves for (A) progression-free survival and (B) overall survival. HR, hazard ratio.

Fig 3.

Improvement rates for quality of life (Functional Assessment of Cancer Therapy – Lung [FACT-L] total score and trial outcome index [TOI]) and symptom improvement (Lung Cancer Subscale [LCS] and pulmonary symptom improvement [PSI]). OR, odds ratio.

Fig 4.

Kaplan-Meier curves for (A) progression-free survival and (B) overall survival by epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) status (exploratory analyses). HR, hazard ratio.