Comparative Efficacy of First-Line Ceritinib and Alectinib in Advanced ALK+ NSCLC: A Cross-Study Indirect Comparison

Background: The second-generation ALK inhibitors, ceritinib and alectinib have demonstrated improved efficacy compared with crizotinib among patients with untreated, advanced ALK+ non-small cell lung cancer (NSCLC). In a phase 3 randomized clinical trial (ALEX), alectinib has shown longer progression-free survival (PFS); in a matching-adjusted indirect comparison (MAIC) analysis, ceritinib was associated with lower hazard of progression or death. In the absence of head-to-head trials, this study indirectly compared efficacy outcomes between ceritinib and alectinib as the first-line treatments for advanced ALK+ NSCLC. Methods: An anchor-based indirect comparison was conducted to compare PFS between ceritinib and alectinib using crizotinib as the common anchor (Bucher et al., 1997). Data on relative efficacy of alectinib vs. crizotinib from the published data of the ALEX trial (Peters et al., 2017) and results from an MAIC of ceritinib vs. crizotinib were used. Using patient level data from ASCEND-4 (NCT01828099) and published aggregate data from PROFILE 1014 (Solomon et al., 2014), the MAIC analysis compared PFS between ceritinib and crizotinib, while adjusting for cross-trial difference in patient baseline characteristics. In the MAIC, ceritinib was associated with improved PFS compared to crizotinib (hazard ratio [HR] 0.64, 95% confidence interval [95% CI] 0.47 to 0.87). Results: In the three studied clinical trials, similar number of patients from each treatment arm were included - 189 patients received ceritinib in ASCEND-4, 323 patients received crizotinib across two separate trials (172 from PROFILE 1014 and 151 from ALEX), and 152 patients received alectinib in ALEX. In the anchor-based comparison, alectinib showed a 22% lower hazard of progression or death compared to ceritinib (HR 0.78, 95% CI 0.50 to 1.23). Conclusions: In this cross-study indirect comparison, the second-generation ALK inhibitor ceritinib had superior PFS compared with crizotinib in patients with untreated, advanced ALK+ NSCLC. Between the two second-generation treatments of ceritinib and alectinib, the PFS was comparable with alectinib having numerically lower hazard of progression or death. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation. Funding: Novartis Pharmaceuticals Corporation. Disclosure: C.P.K. Chan: Employee: Novartis Pharmaceuticals Corporation, Hong Kong, China. J. Li, W. Tang, I. Bocharova, J. Signorovitch: Employee: Analysis Group, Inc., a company that has received consulting fees from Novartis Pharmaceuticals Corporation. S. Knoll: Employee: Novartis Pharmaceuticals Corporation; Stock, other ownership interest: Novartis, GSK, Roche, Merck KGA, Gilead, Incyte.