Solomon BJ, et al. - Researchers present the final overall survival (OS) results of the phase 3 PROFILE 1014 trial that compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) –positive advanced nonsquamous non–small-cell lung cancer. Crizotinib was found to be beneficial in prolonging survival in this patient population and the final analysis of the PROFILE 1014 study provides a new benchmark for OS in patients with ALK-rearranged non–small-cell lung cancer.

Methods

• Oral crizotinib 250 mg twice daily (n=172) or intravenous pemetrexed 500 mg/m² plus cisplatin 75 mg/m² or carboplatin (area under the concentration–time curve of 5 to 6 mg·mL/min) every 3 weeks for a maximum of six cycles (n=171) was randomly administered to patients.
• Following disease progression, crossover to crizotinib was permitted.
• Researchers analyzed OS using a stratified log-rank test and a prespecified rank-preserving structural failure time model to account for crossover.

Results

• For both arms, the median follow-up duration for OS was approximately 46 months.
• Data showed that, in the chemotherapy arm, crizotinib was received by 144 patients (84.2%) in subsequent lines.
• The observed hazard ratio for OS was 0.760 (95% CI, 0.548 to 1.053; two-sided P=.0978).
• Researchers found that median OS was not reached (NR) with crizotinib (95% CI, 45.8 months to NR) and 47.5 months with chemotherapy (95% CI, 32.2 months to NR).
• At 4 years, survival probability was 56.6% (95% CI, 48.3% to 64.1%) with crizotinib and 49.1% (95% CI, 40.5% to 57.1%) with chemotherapy.
• An improvement in OS was noted after crossover adjustment that favored crizotinib (hazard ratio, 0.346; 95% bootstrap CI, 0.081 to 0.718).
• Crizotinib-treated patients who received a subsequent ALK tyrosine kinase inhibitor had the longest OS.
• Researchers found no new safety signals.