Comparative Efficacy of Ceritinib and Crizotinib as Initial ALK-Targeted Therapies in Previously Treated Advanced NSCLC: An Adjusted Comparison with External Controls

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ALK; NSCLC; ceritinib; crizotinib; indirect comparison.