Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor for the treatment of advanced ALK+ non-small cell lung cancer (NSCLC). In June 2016, the international EAP was opened to enable access to brigatinib prior to commercial launch for patients with unmet medical need, including those who had exhausted available therapies or were unable to participate in a clinical study. This retrospective analysis evaluated real-world treatment duration using brigatinib EAP shipment and discontinuation data.
This analysis included data from patients with locally advanced or metastatic ALK+ NSCLC who were resistant or intolerant to at least one ALK inhibitor and had received brigatinib across multiple lines of therapy through the EAP between July 2016 and Nov 7, 2018; most patients were European. Treatment duration was recorded for patients with confirmed discontinuation, as stated on their discontinuation forms. Discontinuation was assumed for patients without confirmed discontinuation if there was a gap of > 120 days between data cutoff and last medication shipment date. Time to treatment discontinuation was estimated from Kaplan-Meier curves. Subgroup analyses were conducted based on whether patients had received prior alectinib, ceritinib, or lorlatinib.
A total of 604 patients (42.4% male; median age, 58.0 years) received brigatinib, with the majority receiving brigatinib as a 3+ line agent. Across all lines of therapy, median time to brigatinib discontinuation was 10.95 months (95% CI 8.65 − 13.88). Median time to discontinuation (95% CI) was 8.72 months (7.50 − 14.93) after alectinib (N = 111), 10.33 months (8.13 − 13.62) after ceritinib (N = 249) and 7.5 months (4.47−NE) after lorlatinib (N = 37). Few patients reported discontinuation due to adverse events (N = 4, 0.7%).
In the real world, despite a heterogeneous patient population treated with multiple prior ALK inhibitors, time to discontinuation of brigatinib (from all lines) was almost one year. Although complete disease progression status of the patients was absent, this time-to-discontinuation analysis indicates encouraging benefit with a manageable safety profile for brigatinib.
Jane Kondejewski, PhD, SNELL Medical Communicaiton, Inc.
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
M.M. Lin, X. Pan, P. Hou, S. Allen, P. Baumann: Employee: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited which funded this study. M.J. Hochmair: Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche; Consulting, advisory roles: Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche.