Long-term outcomes and persistent toxicities following BRAF/MEK inhibitor therapy for advanced melanoma
Document Type
Journal Article
Publication Title
European Journal of Cancer
Volume
194
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
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.
DOI
10.1016/j.ejca.2023.113354
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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