1,653
Views
13
CrossRef citations to date
0
Altmetric
Respiratory

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

, , , , , , , & show all
Pages 569-576 | Received 24 May 2018, Accepted 04 Sep 2018, Published online: 05 Oct 2018
 

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.

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.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 681.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.