Phase 3 study of first-line crizotinib vs pemetrexed−cisplatin/carboplatin (PCC) in East Asian patients (pts) with ALK+ advanced non-squamous non-small cell lung cancer (NSCLC).

9058 Background: The phase 3 study PROFILE 1014 showed a superior outcome of crizotinib over PCC in ALK+ NSCLC. A phase 3 study of similar design (ongoing; NCT01639001) was conducted in an East Asian population in China, Hong Kong, Malaysia, Taiwan, and Thailand. Methods: The study was designed to detect an improvement in median PFS from 6.4 to 10 mo with 80% power and 1-sided type I error of 0.025. Between Sep 2012 and Jul 2014, 207 pts with previously untreated ALK+ advanced NSCLC were randomized 1:1 (stratification: ECOG PS 0/1 vs 2) to receive crizotinib 250 mg PO BID (n = 104) or pemetrexed 500 mg/m2 with either cisplatin 75 mg/m2 or carboplatin AUC 5–6, IV q3w for ≤ 6 cycles (n = 103). Continuation of/crossover to crizotinib after PD (per independent radiological review) was allowed. The primary endpoint was PFS; key secondary endpoints were ORR, OS, safety, and PROs. Results: In the crizotinib and PCC arms, respectively, 91% and 93% were Han Chinese, 95% and 95% had ECOG PS 0/1, and 20% and 31% had brain metastases. The study met its primary objective: crizotinib significantly prolonged PFS vs PCC (HR: 0.40; 95% CI: 0.29–0.57; 1-sided P < 0.0001; median 11.1 and 6.8 mo). The ORR was significantly higher with crizotinib (87.5% vs 45.6%; 2-sided P < 0.0001). At data cutoff, 82 pts (80%) on PCC had crossed over to crizotinib and 59% of pts (122/207) remained in follow-up. With only 35% of OS events, there was a numerical (not statistically significant) improvement in OS with crizotinib (HR: 0.90; 95% CI: 0.56–1.45; 1-sided P = 0.33). Crizotinib and PCC safety profiles were consistent with those previously published. The most common all-causality AEs with crizotinib were elevated transaminases (69%), diarrhea (59%), and vision disorder (56%); the most common grade 3/4 AEs were neutropenia (16%) and elevated transaminases (12%). Two grade 5 AEs (death of unknown cause, interstitial lung disease) were considered crizotinib-related. Conclusions: These results confirm the findings from PROFILE 1014 and demonstrate that first-line crizotinib significantly improves PFS and ORR vs PCC in an East Asian population with ALK+ advanced NSCLC with an acceptable safety profile. Clinical trial information: NCT01639001.