Combination of pembrolizumab plus temozolomide therapy in unresectable and advanced melanoma: a multicenter retrospective analysis in China

BACKGROUND: This study aimed to evaluate the effect of anti-PD-1 combined with temozolomide as front-line therapy in patients with unresectable advanced melanoma. METHODS: The records of patients with unresectable advanced melanoma first treated with pembrolizumab plus temozolomide, pembrolizumab alone, or temozolomide-based chemotherapy at three cancer centers from May 2018 to February 2020 were reviewed. Patients were followed up until death or October 30, 2020. Data were retrospectively reviewed and statistically analyzed for the best objective response rate (ORR) and progression-free survival (PFS), as well as toxicities. RESULTS: Sixty-nine individuals were identified, including 28 (40.6%) with acral melanoma, 18 (26.1%) with cutaneous melanoma, 21 (30.4%) with mucosal melanoma, and two (2.9%) with unknown primary melanoma. The ORR of pembrolizumab plus temozolomide (8/20, 40.0%) in advanced melanoma was higher than pembrolizumab (3/24, 12.5%) and chemotherapy (1/25, 4.0%) alone as front-line therapies. The median PFS of pembrolizumab plus temozolomide as front-line therapy for advanced melanoma was 9.8 months [95% confidence interval (CI): 1.7–17.9 months], which was a significant improvement on the chemotherapy PFS of 4.2 months (95% CI: 2.6–5.8 months) [hazard ratio (HR) 0.415, 95% CI: 0.185–0.931, P=0.033]. The median PFS of pembrolizumab was 6.2 months (95% CI: 2.5–9.9), with no significant difference compared with chemotherapy (HR 0.647, 95% CI: 0.334–1.252, P=0.196). CONCLUSIONS: Combining anti-PD-1 with temozolomide has better efficacy than temozolomide-based chemotherapy or anti-PD-1 alone for advanced melanoma treatment without increasing toxicity. Therefore, anti-PD-1 combined with temozolomide may be preferentially used as a front-line regimen for unresectable advanced melanoma.