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.

Keywords:

• ALK + NSCLC
• Brigatinib
• Ceritinib
• Alectinib
• Indirect comparison

Transparency

Declaration of funding

This work was supported by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of financial/other relationships

K. Reckamp has received consulting fees from Takeda Pharmaceutical Company Limited. H. M. Lin, J. Huang, H. Huang, W. Reichmann, and D. Kerstein are employees of Takeda Pharmaceutical Company Limited and own stock/stock options. I. Proskorovsky, S. Krotneva, and J. Lee are current employees of Evidera, Inc., which has received consultancy fees from Takeda. A CMRO peer reviewer on this manuscript declares lectureship honoraria paid to their institution by Novartis and F.Hoffman-La Roche. Other CMRO peer reviewers on this manuscript have no financial/other relationships to disclose.

Acknowledgments

Editorial support was provided by Peloton Advantage, LLC, Parsippany, NJ, and funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.