‘Second Adjuvant’ Therapy With a BRAF/MEK Inhibitor Delayed Recurrence, Increased Toxicity Among Patients With BRAF-Mutated Melanoma

Study results demonstrated that ‘second adjuvant’ therapy with a BRAF/MEK inhibitor improved recurrence-free survival (RFS) at the cost of toxicity among patients with BRAFV600 (BRAF)-mutated melanoma who experienced disease recurrence after treatment with an adjuvant PD-1–based immunotherapy.

“Anti-PD-1 antibodies and BRAK/MEK inhibitors reduce the risk of recurrence for patients with resected stage III melanoma,” stated Amelia M. Taylor, MD, Melanoma Institute Australia, The University of Sydney, Australia, and coauthors. “[BRAF-]mutated melanoma patients who recur with isolated disease following adjuvant therapy may be suitable for ‘second adjuvant' treatment after local therapy.”

In this study, researchers collected and compared patient characteristics and outcome data from 73 patients with BRAF-mutated melanoma who either failed on PD-1–based immunotherapy and underwent definitive local therapy followed by adjuvant treatment with dabrafenib or trametinib (n = 61) or failed PD-1–based immunotherapy and underwent definitive local therapy, which was not followed by ‘second adjuvant’ treatment (n = 12). 

After a median follow-up of 26.1 months, analysis found that 66% of patients recurred on PD-1–based therapy. Median duration of therapy was 11.8 months and 72% of patients required dose adjustments. Median RFS was 30.8 months in the ‘second adjuvant’ arm and 4 months in the control arm (hazard ratio [HR] 0.35; P = .014), largely driven by a delay in early recurrence with no difference in overall survival (P = .59). Grade ≥ 3 treatment toxicity was experienced by 23% of patients and 38% of patients permanently discontinued treatment due to toxicity.

“This is the first study examining outcomes of ‘second adjuvant’ targeted therapy for melanoma, after failure of adjuvant PD-1 based immunotherapy [and] data suggest a short-term improvement in RFS, but at the cost of toxicity,” concluded Dr Taylor and coauthors. “Alternative strategies and more data on sequencing adjuvant therapies are required to improve outcomes.”

Source: 

Taylor AM, McKeown J, Dimitriou F, et al. Efficacy and safety of ‘second adjuvant’ therapy with BRAF/MEK inhibitors after local therapy for recurrent melanoma following adjuvant PD-1 based immunotherapy. Eur J Cancer. Published online: January 19, 2024. doi:10.1016/j.ejca.2024.113561