The Role of Treatment Sequencing with Immune-Checkpoint Inhibitors and BRAF/MEK Inhibitors for Response and Survival of Patients with BRAFV600-Mutant Metastatic Melanoma-A Retrospective, Real-World Cohort Study.

The advent of immune-checkpoint inhibitors (CPI) and BRAF/MEK-directed targeted therapy (TT) has improved the treatment landscape of patients with BRAFV600-mutant metastatic melanoma. While TT allows for rapid disease control, the development of secondary TT resistance limits the duration of responses. Responses to CPI have a slower onset but can be durable in a subset of patients. To date, little prospective data is available for the optimal sequencing of these agents in melanoma patients. In this retrospective, single-center, real-world analysis, we identified 135 patients with BRAF-mutated, metastatic melanoma who received consecutive treatment with TT followed by CPI, or vice versa, as first and second-line therapy, respectively. We collected data on clinical-pathological factors, treatment duration, best overall response, progression-free survival and overall survival (OS). Our data revealed that front-line treatment with CPI, followed by TT, showed a non-significant trend towards better OS compared to front-line TT (median OS: 35.0 vs. 18.0 months,