Phase II trial on nivolumab plus hypofractionated radiotherapy in patients with metastatic mucosal melanoma: PORTER-M3 trial.

Background: The response rate of nivolumab monotherapy for mucosal melanoma is only ∼20%. The objective of this phase II trial was to evaluate the efficacy and safety of nivolumab in combination with radiotherapy for metastatic mucosal melanoma. Patients and methods: The eligibility criteria were: histological diagnosis of metastatic mucosal melanoma, Eastern Cooperative Oncology Group performance status of 0 or 1, and presence of measurable lesions. Patients received nivolumab with concurrent radiotherapy for measurable lesions, for a total dose of 25 Gy in five fractions per week. The primary endpoint was the response rate of all lesions (overall response rate, ORR). The study was considered to have met its primary endpoint if at least 6 of the 17 patients had a response (ORR ≥35.3%). The secondary endpoints were the disease control rate, progression-free survival, overall survival, and toxicity. Results: Eighteen patients were enrolled, and 17 were evaluable for efficacy. The ORR was 41.2%, with two patients showing complete response, five partial response, and four stable disease. The median progression-free and overall survival were 4.9 months [95% confidence interval (CI) 2.2-15.1 months] and 20.1 months (95% CI 7.5-31.5 months), respectively. Immune-related adverse events of grades 3 or 4 occurred in 35.2% (6/17) of the patients. The radiation-related adverse events were grade 3 radiation dermatitis in one patient and grade 3 radiation pneumonitis in one patient. Conclusions: Concurrent radioimmunotherapy consisting of nivolumab and radiotherapy showed promising efficacy with a manageable safety profile in patients with metastatic mucosal melanoma, warranting further evaluation in large studies.