A Single Center Real-world Observational Study of Response to Dacarbazine or Dacarbazine Combinations in Metastatic Melanoma Refractory to Immunotherapy

BACKGROUND/AIM: Outcomes in cutaneous melanoma have improved significantly with the introduction of immune checkpoint inhibitors (ICIs). However, a subset of patients remains refractory to ICIs. Dacarbazine is a well-established chemotherapy option for melanoma, and National Institute for Health and Clinical Excellence (NICE) guidelines continue to recommend it as a systemic anticancer treatment for unresectable stage III and IV melanoma. With the introduction of ICI and targeted treatments, BRAF/MEK inhibitors, the role of conventional chemotherapy has become less clear. This study aimed to determine real-world outcomes with dacarbazine, alone or in combination chemotherapy, in patients with advanced melanoma treated in this setting. PATIENTS AND METHODS: We conducted a retrospective single-centre observational study of patients with unresectable stage IV melanoma treated with dacarbazine alone or in combination with cisplatin between January 2014 and June 2023. Outcomes included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and time-to-treatment failure (TTF), assessed using RECIST 1.1 criteria where available. RESULTS: Forty patients were included. Median age was 64 years (range=28-82 years). Median OS was 7.6 months, median PFS was 2.9 months, and median TTF was 3.5 months. DCR was 37.8%, with partial response in 27% and stable disease in 10.8%. No complete responses were observed and 30% of patients survived ≥12 months. CONCLUSION: Dacarbazine-based chemotherapy retains modest activity in selected patients with advanced melanoma in the immunotherapy-refractory setting. Further multicenter studies are required to define predictive biomarkers and optimize patient selection.