Abstract 1392P
Background
Brigatinib is a next-generation ALK inhibitor developed in ALK+ NSCLC initially pretreated with crizotinib and now in first line setting. The objective of this study was to assess efficacy and tolerance of brigatinib administrated in the French early access program (EAP).
Methods
This retrospective multicentric study included ALK+ advanced NSCLC patients pretreated with at least one anti-ALK tyrosine-kinase inhibitor (TKI), enrolled in the brigatinib French EAP. Primary endpoint was investigator-assessed progression-free survival (PFS). The results cover the entire EAP period and are an update of the first data presented at ASCO 2019 (abstract #9045).
Results
184 patients were included by 66 centers in France: median age: 60 ±12.7 years; never smokers: 78.3%; adenocarcinoma: 97.8%; median number of previous lines: 3±1.3 and of ALK inhibitors : 2±0.5 (crizotinib: 91.8%, ceritinib: 85.3%, alectinib: 9.2%). 50.0% of patients had performance status 0-1 and 67.6% more than 3 metastatic sites (brain metastases (BM): 71%, carcinomatous meningitis 7.1%). Overall response rate was 43.2%. With a median follow up of 27.5 months (95%CI 25-4-29.4), median duration of brigatinib treatment was 4.9 months (95%CI 4.1-5.9) with 42.4% and 23.4% patients on treatment at 6 and 12 months. Median PFS was 4.8 months (95%CI: 3.8-5.6). OS from brigatinib initiation was 19.4 months (95%CI: 15.6-24.5) while 79.1% and 18.2% of patients received 1 and 2 post-brigatinib treatment, respectively. In patients with and without BM, OS was 21.8 (95%CI 15.6-35.4) and 18 (95%CI 12.4-24) months, respectively. For patients who received 1 (n=23), 2 (n=146) or 3 (n= 15) TKI before brigatinib start, OS from brigatinib initiation was 15.6 (95%CI 9.7-NR), 19.4 (95%CI 15.7-28.7) and 21.8 (3.3-39) months, respectively. 10.3% of patients had permanent treatment discontinuation due to treatment-related adverse events and 9.7% underwent dose adjustments without definitive interruption.
Conclusions
The analysis of the EAP confirms the efficacy of brigatinib in a cohort of heavily pretreated for ALK-positive advanced NSCLC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Groupe Français de Pneumo-Cancérologie.
Funding
Takeda.
Disclosure
R. Descourt: Advisory/Consultancy, Travel/Accommodation/Expenses, symposium and lectures: Takeda; Advisory/Consultancy, Travel/Accommodation/Expenses, symposium and lectures: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses, symposium and lectures: Pfizer; Advisory/Consultancy, symposium and lectures: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses, symposium and lectures: MSD; Advisory/Consultancy, symposium and lectures: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses, symposium and lectures: AstraZeneca. M. Pérol: Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: Roche genentech , Pierre Fabre, AstraZeneca, Takeda; Advisory/Consultancy, symposium and lectures: Eli Lilly; Advisory/Consultancy, symposium and lectures: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: Boehringer Ingelheim; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy, symposium and lectures: MSD; Advisory/Consultancy, symposium and lectures: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: Takeda; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: Chugaï. D. Planchard: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses, clinical trial research: AstraZeneca; Honoraria (institution), Advisory/Consultancy, clinical trial research: BMS; Honoraria (institution), Advisory/Consultancy, clinical trial research: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Celgene; Advisory/Consultancy, clinical trial research: Daïchi Sankyo; Honoraria (institution), Advisory/Consultancy, clinical trial research: Lilly; Honoraria (institution), Advisory/Consultancy, clinical trial research: Merck; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses, clinical trial research: Novartis; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses, clinical trial research: Pfizer; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: prIME oncology; Honoraria (institution), Advisory/Consultancy: Peer CME; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses, clinical trial research: Roche; Advisory/Consultancy: Samsung. G. Rousseau-Bussac: Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Boehringer Ingelheim; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: Janssen Cilag; Non-remunerated activity/ies: Lilly; Non-remunerated activity/ies: Mundipharma; Non-remunerated activity/ies: MSD; Non-remunerated activity/ies: Novartis; Non-remunerated activity/ies: Pfizer. B. Mennecier: Advisory/Consultancy, symposium and lectures: Roche; Advisory/Consultancy, symposium and lectures: AstraZeneca; Advisory/Consultancy, symposium and lectures: Pfizer; Advisory/Consultancy, symposium and lectures: Boehringer Ingelheim; Advisory/Consultancy, symposium and lectures: MSD; Advisory/Consultancy, symposium and lectures: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy, symposium and lectures: Takeda; Advisory/Consultancy, symposium and lectures: Amgen. M. Wislez: Non-remunerated activity/ies, personnal fees: Roche; Non-remunerated activity/ies, personnal fees: AstraZeneca; Non-remunerated activity/ies, personnal fees: Boehringer Ingelheim; Non-remunerated activity/ies, personnal fees: BMS; Non-remunerated activity/ies, personnal fees: MSD; Non-remunerated activity/ies, personnal fees: Pfizer. J. Cadranel: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda; Advisory/Consultancy: Roche. F. Guisier: Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD. R. Schott: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Ipsen. J. Arrondeau: Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Travel/Accommodation/Expenses: Takeda. J.B. Auliac: Non-remunerated activity/ies, personnal fees: AstraZeneca; Non-remunerated activity/ies, personnal fees: MSD; Non-remunerated activity/ies, personnal fees: BMS; Non-remunerated activity/ies: Roche; Non-remunerated activity/ies: Boehringer Ingelheim. C. Chouaid: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, symposium and lectures: Lilly; Advisory/Consultancy, symposium and lectures: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: Boehringer Ingelheim; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: MSD; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), symposium and lectures: Takeda; Advisory/Consultancy: Janssen Cilag; Advisory/Consultancy: Bayer. All other authors have declared no conflicts of interest.