Comparative efficacy of first-line ceritinib and crizotinib in advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer: an adjusted indirect comparison with external controls

Abstract

Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.

Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI]) = 0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value = 0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.

Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC.

Keywords:

• ALK-positive NSCLC
• Ceritinib
• Crizotinib
• Matching-adjusted indirect comparison

Transparency

Declaration of funding

This work was supported by Novartis Pharmaceuticals Corporation.

Declaration of financial/other relationships

J.L., I.B., W.T., and J.S. are employees of Analysis Group, Inc., which has received consultancy fees from Novartis Pharmaceuticals Corporation. S.K. is an employee of Novartis Pharmaceuticals Corporation and may own stock/stock options. A CMRO peer reviewer on this manuscript is an employee of Foundation Medicine, a wholly owned subsidiary of Roche Pharmaceuticals, which makes and distributes alectinib, an ALK inhibitor. Other CMRO reviewers have no relevant financial or other relationships to disclose.

Acknowledgments

The authors gratefully acknowledge Gero Struebbe, an employee of Novartis, for his technical assistance during the design of this study. Medical writing assistance was provided by Gloria DeWalt, PhD, an employee of Analysis Group, Inc.