医学
不利影响
内科学
黑色素瘤
回顾性队列研究
无进展生存期
毒性
肿瘤进展
外科
肿瘤科
队列
癌症
放射治疗
化疗
癌症研究
作者
Rachel S. Goodman,Lorenza Di Guardo,Andrea Maurichi,Brendan Kirwin,Adnan Khattak,Vito Vanella,Joanna Lee,Aleigha Lawless,J. Czapla,Andrea Spagnoletti,Margherita Ambrosini,Elisabeth Livingstone,Georgina V. Long,Ryan J. Sullivan,Matteo S. Carlino,Victoria Atkinson,Claudia Trojanello,Paolo A. Ascierto,Dirk Schadendorf,Lydia Warburton,Alexander M. Menzies,Mario Santinami,Douglas B. Johnson
标识
DOI:10.1016/j.ejca.2023.113354
摘要
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.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.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.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.
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