Long-term outcomes and persistent toxicities following BRAF/MEK inhibitor therapy for advanced melanoma
Abstract
Background: Recent studies have shown that approximately 20% of patients have 4–5 year progression free survival (PFS) on BRAF/MEK inhibitors. The long-term safety and efficacy in these patients with more durable responses have not been studied. Methods: This retrospective multicenter cohort study assessed response, progression, and adverse events in patients from eight institutions in four countries with > 4-year PFS following BRAF/MEK inhibitors. Results: Among 146 patients, 112 (76.7%) remained progression-free at median follow-up of 7.8 years from treatment start; 131 (89.7%) were alive. Among progressors (n = 34), 21 (62%) were on treatment at progression. Among those who discontinued treatment for reasons other than progression (toxicity, preference, etc.) (n = 68, with median 49 months treatment duration), 13 (19%) progressed (median 15.3 months from treatment cessation to progression). Surgery or radiation for single-organ progression resulted in durable benefit in 11 of 22 patients (50%). Subsequent systemic therapy included immune therapy (24% responded) and BRAF/MEK rechallenge (56% responded). Thirteen (8.9%) patients had ongoing toxicities at last follow-up, 10 (77%) of which remained on active treatment; all cardiac adverse events had resolved (n = 9). Twenty-four (16.4%) patients developed any new primary cancer, and 28 (19%) patients experienced other major health events. Conclusions: Over 75% of patients with 4-year PFS from BRAF/MEK inhibitors had continued durable antitumor responses after nearly 8-year median follow-up, with similar results in patients who discontinued therapy for reasons other than progression. Long-term toxicities were uncommon and low-grade. These findings highlight the often-favourable outcomes in patients with extended benefit from BRAF/MEK inhibitors.
Document Type
Journal Article
Date of Publication
11-1-2023
Volume
194
Publication Title
European Journal of Cancer
Publisher
Elsevier
School
School of Medical and Health Sciences
RAS ID
60690
Funders
National Health and Medical Research Council / Funding information: https://doi.org/10.1016/j.ejca.2023.113354
Copyright
subscription content
Comments
Goodman, R. S., Di Guardo, L., Maurichi, A., Kirwin, B., Khattak, A., Vanella, V., . . . Johnson, D. B. (2023). Long-term outcomes and persistent toxicities following BRAF/MEK inhibitor therapy for advanced melanoma. European Journal of Cancer, 194, article 113354. https://doi.org/10.1016/j.ejca.2023.113354