Long-Term Outcomes and Persistent Toxicities Following BRAF/MEK Inhibitor Therapy for Advanced Melanoma
Menée à partir de données portant sur 146 patients atteints d'un mélanome de stade avancé (durée médiane de suivi : 7,8 ans), cette étude de cohorte rétrospective évalue l'efficacité, du point de vue de la survie sans progression et du taux de réponse, et la toxicité des inhibiteurs de BRAF/MEK
Background: Recent studies have shown that approximately 20% of patients have 4-5 year 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 8 institutions in 4 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). 13 (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). 24 (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-favorable outcomes in patients with extended benefit from BRAF/MEK inhibitors.