First-Line Treatment of Advanced or Metastatic Mucosal Melanoma Without BRAF, KIT, or NRAS Mutation
Patients with mucosal melanoma that is advanced, unresectable, or metastatic — and whose tumour tests negative for BRAF, KIT, and NRAS mutations — represent a distinct clinical subgroup with limited targeted-therapy options. Selecting an appropriate first-line regimen in this setting requires careful consideration of the available evidence.
Clinical scenario
Advanced, unresectable, or metastatic mucosal melanoma confirmed to lack BRAF, KIT, and NRAS mutations. Evidence supports the use of chemotherapy combined with antiangiogenic agents as a viable option in this population.
First-line approach
The evidence-based first-line approach centres on antiangiogenic-based combination strategies, incorporating agents that target angiogenic pathways alongside immunotherapy or cytotoxic chemotherapy — with several distinct regimen options available depending on the clinical context.
Full regimen options, sequencing, and dosing guidance are in the complete protocol →
References
DOI: 10.1200/EDBK-25-473858
- These findings suggest that chemotherapy combined with antiangiogenic agents may be viable for unresectable or advanced MM.
- A phase Ib study evaluated toripalimab, a humanized anti–PD-1 monoclonal antibody, in combination with the VEGF receptor inhibitor axitinib for advanced melanoma.
- A phase II trial evaluated atezolizumab (anti–PD-1 monoclonal antibody) combined with bevacizumab (VEGF monoclonal antibody) in advanced MM, enrolling 22 patients.
- Zhao et al evaluated the efficacy and safety of camrelizumab (humanized anti–PD-1 antibody), in combination with apatinib (a VEGFR tyrosine kinase inhibitor), for advanced MM.
- Combined anti–CTLA-4 and anti–PD-1 checkpoint inhibition achieves the highest 5-year OS rate among therapies for advanced melanoma but is also associated with the highest incidence of immune-related adverse events.
- A Chinese retrospective study presented at the 2018 European Society for Medical Oncology Congress reported a PFS of 4 months for first-line therapy (dacarbazine + cisplatin + endostar) and 2 months for second-line treatment (paclitaxel + carboplatin + bevacizumab).
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