PD-1/PD-L1 抑制剂在 Merkel 细胞癌患者中的疗效和安全性：系统评价和 Meta 分析。

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

机构信息

Federal University of Pará, R. Augusto Corrêa, 01, PA, Belém, 66075-110, Brazil.

Lutheran University of Brazil, Canoas, Rio Grande Do Sul, 92425-020, Brazil.

出版信息

BMC Cancer. 2024 Nov 6;24(1):1357. doi: 10.1186/s12885-024-13129-1.

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.

背景

Merkel 细胞癌（MCC）是一种罕见且侵袭性的神经内分泌皮肤癌，其转移率很高。新出现的证据表明，PD-L1/PD1 阻断作为 MCC 的一种治疗选择具有前景。然而，这种方法治疗 MCC 的疗效和安全性仍不完全清楚。本系统评价和荟萃分析旨在分析 PD-1/PD-L1 阻断治疗 MCC 患者的疗效和安全性。

方法

检索 PubMed、Cochrane 和 Embase 以评估接受 PD-1/PD-L1 治疗的 MCC 患者的研究。估计的结果是总缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和治疗相关不良事件（TRAEs）。我们使用 RStudio v4.4.2 软件进行荟萃分析。

结果

共纳入 13 项不同研究的 14 项报告，共纳入 615 例患者。中位年龄为 64-77 岁。中位随访时间为 7.9-59.3 个月。24 个月和 36 个月时的汇总 OS 率分别为 65.05%（95%CI 44.04-81.49）和 59.58%（95%CI 39.62-76.81），而 6、12 和 36 个月时的汇总 PFS 率分别为 51.78%（95%CI 37.83-65.45）、46.12%（95%CI 29.44-63.72）和 28.73%（95%CI 16.57-45.02）。DCR 比例为 61.65%（95%CI 54.85-68.03），ORR 为 53.79%（95%CI 47.80-59.68）。任何等级 TRAEs 的频率为 61.72%（95%CI 45.75-75.51），等级≥3 的 TRAEs 频率为 17.60%（95%CI 12.28-24.57）。