Comparative Efficacy of Ceritinib and Crizotinib as Initial ALK-Targeted Therapies in Previously Treated Advanced...

Crizotinib and ceritinib have been developed to treat advanced or metastatic NSCLC by inhibiting anaplastic lymphoma receptor tyrosine kinase gene (ALK). No randomized trial has compared these treatments head-to-head. We compared efficacy outcomes between patients receiving ceritinib and an external control group receiving crizotinib, both as initial ALK-targeted therapies for previously treated advanced or metastatic ALK-positive NSCLC.

Individual patient data for the ceritinib-treated patients were drawn from two single-arm trials (ASCEND-1 and ASCEND-3); published summary data for the crizotinib-treated patients were extracted from three trials (PROFILE 1001, PROFILE 1005, and PROFILE 1007). To adjust for cross-trial differences, average baseline characteristics were matched using propensity score weighting. Overall survival (OS), progression-free survival (PFS), and overall response rate were then compared between treatment groups.

Before matching, the ceritinib-treated patients (n = 189) were significantly different from the crizotinib-treated patients (n = 557) in the distribution of race and number of prior regimens. After matching, all available baseline characteristics were balanced. Compared with crizotinib, ceritinib was associated with longer OS (hazard ratio = 0.59, 95% confidence interval: 0.46-0.75) and longer PFS (median 13.8 versus 8.3 months, hazard ratio = 0.52, 95% confidence interval: 0.44-0.62) in Cox proportional hazards models. The 12-month OS was 82.6% with ceritinib and 66.0% with crizotinib in a Kaplan-Meier analysis (log-rank p < 0.001). There was no significant difference in overall response rate between ceritinib and crizotinib.

In an adjusted comparison across separate clinical trials, ceritinib was associated with prolonged OS and PFS compared with crizotinib when used as initial ALK-targeted therapy for previously treated ALK-positive NSCLC.