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Alectinib Efficacy Post-Brigatinib Against Advanced ALK+ Non-Small Cell Lung Cancer (BrigALK2-GFPC 02-2019 Study)

Year: 2025

Type: article

Abstract: Background: Brigatinib and alectinib are next-generation anaplastic lymphoma kinase inhibitors (ALKis) showing efficacy against naïve and post-crizotinib-treated advanced ALK + non-small-cell lung cancers (NSCLCs). Real-world data on alectinib efficacy after brigatinib failure are lacking. Methods: Alectinib efficacy was retrospectively assessed in patients previously treated with brigatinib during an early-access program (EAP) from 1 August 2016 to 21 January 2019. The primary endpoint was alectinib median progression-free survival (mPFS) according to local investigators. Results: Among the 183 patients included in the brigatinib EAP, 92 (50.3%) received ≥ 1 agent(s) post-brigatinib; 30 (16.4%) received alectinib, 19 (10.4%) immediately post-brigatinib; 11 (6%) after ≥ 1 other treatment line(s). With median follow-up at 25.5 (95% CI: 10.6– 30.5) months, mPFS on brigatinib for the study population (n = 30) was 13.6 (95% CI: 6.3– 17.7) months. For patients given alectinib immediately post-brigatinib, mPFS and median overall survival (mOS) were 4.8 (95% CI: 2.0– 12.5) and 27 (95% CI: 12.5–not reached (NR)) months, respectively. In this subgroup, brigatinib was discontinued for toxicity or progression for 5/19 (26%) or 14/19 (74%) patients, with mPFS lasting 12.5 (95% CI: 3.3– 17.9 and 3.4 (95% CI: 0.9– 9.2) months, respectively. For patients receiving ≥ 1 agent(s) between brigatinib and alectinib, with median follow-up at 13.3 (95% CI: 2.3– 31.5) months, mPFS and mOS were 5.0 (95% CI: 0.5– 18.8) and 19 (95% CI: 2.3–NR) months, respectively. Conclusion: According to the results of this retrospective real-world study, alectinib post-brigatinib showed limited overall activity but remains an option for patients with advanced ALK + NSCLCs, especially when brigatinib was discontinued because of toxicity. Keywords: alectinib, brigatinib, management, ALK+ non-small cell lung cancer

Source: Lung Cancer Targets and Therapy

DOI: 10.2147/lctt.s522038