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

Merkelcell.org Summary

Immunotherapy is a type of drug that helps the immune system fight cancers like Merkel cell carcinoma (MCC). Multiple studies and clinical trials have shown that immunotherapy can work well for treating MCC that has spread to other parts of the body (metastatic MCC). This large-scale analysis, known as a meta-analysis, combines data from many trials to give stronger and more reliable results. By bringing together information from multiple studies, it provides a clearer understanding of the benefits and risks of immunotherapy. This paper reviewed the results of 13 different prior studies involving 615 patients with metastatic MCC who received immunotherapy. Overall, 54% of patients responded well to the treatment. Three years after starting immunotherapy, 60% of patients were still alive, and 29% had no return of their cancer. However, 18% of patients experienced serious side effects, and 13% had to stop treatment because of these side effects. This meta-analysis confirms that immunotherapy not only helps patients with metastatic MCC live longer but also reduces the risk of their cancer returning, while also noting the potential for serious side effects.

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.