The role of radiotherapy in patients with advanced melanoma failing targeted therapy.

Abstract

Background and purpose: Approximately 50% of patients with metastatic melanoma harbor mutations in the BRAF gene, making them eligible for targeted therapy (TT). However, treatment options become limited once resistance develops. The role of radiotherapy (RT) in this context remains uncertain, and concerns exist regarding toxicity when RT is delivered concurrently with TT. Patient/material and methods: This retrospective study included metastatic melanoma patients treated with RT after experiencing disease progressing on TT between 2015 and 2023. Patients were grouped by subsequent systemic therapy: RT-STOP (discontinued TT), RT-TT (continued TT), and RT-ICI (switched to immune checkpoint inhibitors (ICI)). Study endpoints were progression-free survival (PFS), overall survival (OS), efficacy, and toxicity.

Results: Sixty-three patients were analyzed. Median PFS and OS were 1.9 and 3.1 months. The median OS in RT-STOP, RT-TT, and RT-ICI was 1.7, 4.7, and 3.0 months, while the 1-year OS rate was 4.9, 7.6, and 33.4%, respectively (p = 0.001). RT was well tolerated, with no grade ≥3 adverse events observed and 50.9% of patients derived a local benefit.

Interpretation: In advanced melanoma patients with disease progression on TT, RT was safe and provided a local effect. Although survival outcomes remained suboptimal, continuation of TT beyond progression or transition to ICI following RT was associated with improved OS compared with discontinuation of TT. These results support the role of RT as a safe bridging modality, suggest benefit from treatment beyond progression with TT, and warrant confirmation in prospective trials.