Brigatinib in pretreated patients with ALK-positive advanced NSCLC.

Abstract

9045 Background: Brigatinib is a next-generation ALK inhibitor initially developed in pre-treated ALK+ NSCLC. Data on the efficacy of brigatinib in real world remain rare. Methods: This retrospective multicentric study analyzed ALK-+ advanced NSCLC patients pretreated with at least two tyrosine-kinase inhibitors, including crizotinib, and enrolled in the brigatinib French early access program. The primary endpoint was investigator-assessed progression-free survival (PFS). Results: 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 in 93% patients. 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 (0.06–20.7) months. Median PFS was 6.6 (95% CI, 4.8–9.9) months for the entire population. In the 91 evaluable patients, disease control rate was 78.2% (stable, 28.2%; partial response, 45.7%; complete response, 4.3%). From brigatinib start, median overall survival was 17.2 (95% CI:11.0–not reached) months. Among the 68 patients with progressive disease after brigatinib, CNS was involved in 29.4% of cases. Ten (9.6%) patients had treatment discontinuation due to intolerance or patient request. Median OS from the diagnostic of NSCLC was 75,3 (95% CI, 38,2-174,6) months. Conclusions: This study confirms the efficacy of brigatinib in a cohort of patients heavily pretreated for ALK-+advanced NSCLC. These real-world results are consistent with clinical data reported in clinical trials.