Comparative efficacy of brigatinib versus ceritinib and alectinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell lung cancer

Abstract

Objective: Brigatinib, ceritinib, and alectinib are approved to treat crizotinib-refractory anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC), but no trial has compared them head-to-head. A matching-adjusted indirect comparison (MAIC) was conducted to estimate the relative efficacy of these agents in the crizotinib-refractory setting.Methods: MAIC is a propensity score-type method that adjusts for differences in baseline characteristics between trials to estimate relative efficacy. Analyses were based on patient-level data from the ALTA trial for brigatinib and published summary-level trial data from ASCEND-1 and ASCEND-2 for ceritinib and NP28761 and NP28673 for alectinib. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared.Results: After matching, all key baseline characteristics were balanced between trials. Compared with ceritinib, brigatinib was associated with longer PFS (ASCEND-1: median 15.7 vs 6.9 months, hazard ratio (HR) [95% confidence interval] = 0.38 [0.26–0.57]; ASCEND-2: median = 18.3 vs 7.2 months, HR = 0.33 [0.20–0.56]) and OS (ASCEND-1: not available; ASCEND-2: median 27.6 vs 14.9 months, HR = 0.33 [0.17–0.63]). Versus alectinib, brigatinib was associated with longer PFS (NP28761: median = 17.6 vs 8.2 months, HR = 0.56 [0.36–0.86]; NP28673: median = 17.6 vs 8.9 months, HR = 0.61 [0.40–0.93]); results for OS were inconclusive (NP28761: median = 27.6 vs 22.7 months, HR = 0.70 [0.42–1.16]; NP28673: median = 27.6 vs 26.0 months, HR = 0.66 [0.39–1.09]). ORR was similar.Conclusion: In crizotinib-refractory ALK + NSCLC patients, relative efficacy estimates suggest brigatinib may have prolonged PFS and OS vs ceritinib and prolonged PFS vs alectinib.Trial registration: ClinicalTrials.gov identifier: NCT02094573.Trial registration: ClinicalTrials.gov identifier: NCT01283516.Trial registration: ClinicalTrials.gov identifier: NCT01685060.Trial registration: ClinicalTrials.gov identifier: NCT01871805.Trial registration: ClinicalTrials.gov identifier: NCT01801111.