Brigatinib in patients with ALK-positive advanced non-small-cell lung cancer pretreated with sequential ALK inhibitors: A multicentric real-world study (BRIGALK study)

•Brigatinib is efficient in ALK + NSCLC pretreated with crizotinib or other ALK TKIs.•Real-world data on the efficacy of brigatinib remain rare.•Brigatinib is efficient after progression with ALK TKIs in early access program.•Dose reduction rate in real-world setting was 8.8%. Brigatinib is a next-generation ALK inhibitor initially developed in ALK-positive NSCLC pretreated with crizotinib. This retrospective multicentric study analyzed ALK-positive advanced NSCLC patients pretreated with at least one tyrosine-kinase inhibitor, including crizotinib, and enrolled in the brigatinib French early access program. The primary endpoint was investigator-assessed progression-free survival (PFS). 104 patients were included (mean age, 56.6 years; never smokers, 61.5%; adenocarcinoma, 98.1%). Patients had received a median of 3 previous treatment lines, including at least 2 ALK inhibitors (mainly crizotinib then ceritinib). At brigatinib initiation, 59.1% had performance status 0–1, 51.9% had ≥ 3 metastatic sites, 74.5% had central nervous system metastases (CNS) and 8.8% had carcinomatous meningitis. Median duration of brigatinib treatment was 6.7 (95% CI, 0.06–20.7) months. Median PFS was 6.6 (4.8–9.9) months for the entire population. For patients who received 2, 3–4 and >4 lines of treatment before brigatinib, PFS was 4.3 (2.5–8.9), 10.4 (5.9–13.9) and 3.8 (0.8–7.4) months, respectively. In the 91 evaluable patients, disease control rate was 78.2%. From brigatinib start, median overall survival was 17.2 (11.0–not reached) months. Among the 68 patients with progressive disease after brigatinib, CNS was involved in 29.4% of cases. Median OS from the diagnosis of NSCLC was 75.3 (38.2–174.6) months. These real-world results confirm the efficacy of brigatinib in a cohort of patients heavily pretreated for ALK-positive advanced NSCLC.