Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non–Small Cell Lung Cancer

Abstract

Introduction: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first‐line chemotherapy in prolonging progression‐free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)‐positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population. Methods: In this open‐label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3‐week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration–time curve of 5–6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point. Results: Crizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286–0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6–93.2%) with crizotinib versus 45.6% (95% CI: 35.8–55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient‐reported outcomes were seen in crizotinib‐treated versus chemotherapy‐treated patients. Conclusions: First‐line crizotinib significantly improved PFS, objective response rate, and patient‐reported outcomes compared with standard platinum‐based chemotherapy in East Asian patients with ALK‐positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.