Efficacy and safety of PD-1/PD-L1 inhibitors in patients with Merkel Cell Carcinoma: a systematic review and Meta-analysis

Abstract

Abstract Background Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer characterized by high rates of metastasis. Emerging evidence suggests that PD-L1/PD1 blockade holds promise as a therapeutic option for MCC. However, the efficacy and safety of this approach in treating MCC remain incompletely understood. This systematic review and meta-analysis aims to analyze the efficacy and safety of PD-1/PD-L1 blockade for patients with MCC. Methods PubMed, Cochrane, and Embase were searched for studies evaluating patients with MCC undergoing PD-1/PD-L1 treatment. The estimated outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). We performed the meta-analysis using RStudio v4.4.2 software. Results A total of 14 reports of 13 different studies encompassing 615 patients were included. The median age ranged from 64 to 77 years. Median follow-up ranged from 7.9 months to 59.3 months. Pooled OS rates at 24 and 36 months were 65.05% (95% CI 44.04–81.49) and 59.58% (95% CI 39.62–76.81), respectively, while pooled PFS rates at 6, 12, and 36 months were 51.78% (95% CI 37.83–65.45), 46.12% (95% CI 29.44–63.72), and 28.73% (95% CI 16.57–45.02), in the same order. DCR proportion was 61.65% (95% CI 54.85–68.03) and ORR was 53.79% (95% CI 47.80-59.68). The frequency of TRAEs of any grade was 61.72% (95% CI 45.75–75.51) and for TRAEs of grade ≥ 3 was 17.60% (95% CI 12.28 to 24.57). Conclusions This systematic review and meta-analysis revealed that patients with MCC undergoing treatment with PD-1/PDL-1 showed durable responses with continuous and clinically meaningful survival outcomes. Graphical Abstract

Keywords

• Merkel cell carcinoma
• Skin cancer
• PD-1/PD-L1 inhibitors
• Meta-analysis