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Alectinib Efficacy Post-Brigatinib Against Advanced ALK+ Non-Small Cell Lung Cancer (BrigALK2-GFPC 02-2019 Study)
Renaud Descourt1, Florian Guisier2, Maurice Pérol3
1Hopital La Cavale Blanche, CHU Brest, Brest, France.
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.
Insights
Alectinib showed limited efficacy after brigatinib treatment in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer patients. However, it may be a viable option, particularly if brigatinib was stopped due to toxicity.
Area of Science:
- Oncology
- Pharmacology
Background:
- Brigatinib and alectinib are effective anaplastic lymphoma kinase inhibitors (ALKi) for advanced ALK-positive non-small-cell lung cancer (NSCLC).
- Limited real-world data exists on alectinib's efficacy following brigatinib treatment failure.
Purpose of the Study:
- To assess the real-world efficacy of alectinib in patients with advanced ALK-positive NSCLC who previously received brigatinib.
Main Methods:
- Retrospective analysis of patients treated with alectinib after brigatinib within an early-access program (EAP).
- Primary endpoint: alectinib median progression-free survival (mPFS) assessed by local investigators.
Main Results:
- Of 30 patients who received alectinib post-brigatinib, mPFS was 4.8 months when given immediately after brigatinib.
- Median overall survival (mOS) was 27 months for patients receiving alectinib immediately post-brigatinib.
- Alectinib showed limited activity, especially when other treatments were administered between brigatinib and alectinib.
Conclusions:
- Alectinib demonstrates limited overall activity after brigatinib failure in advanced ALK-positive NSCLC.
- Alectinib remains a potential treatment option, particularly when brigatinib discontinuation was due to toxicity.
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