Outcomes of ipilimumab plus nivolumab in metastatic merkel cell carcinoma: A systematic review and meta-analysis.

Abstract

e21586 Background: Merkel Cell Carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer characterized by high recurrence rates and poor survival outcomes. Conventional treatments often fail to provide durable responses, prompting the need for novel therapeutic approaches. Immune checkpoint inhibitors have emerged as promising options. This meta-analysis aimed to explore the outcomes of ipilimumab plus nivolumab (ipi/nivo) in metastatic MCC patients. Methods: A systematic search was conducted on PubMed, Medline, and Embase following PRISMA guidelines and four studies reporting outcomes of ipi/nivo in metastatic MCC were included after screening of 71 studies. Inter-study variance was assessed using the Der Simonian-Laird Estimator, and pooled analysis was conducted with 95% confidence intervals using the ‘meta’ package in R (version 4.16-2). Results: A total of 80 patients with metastatic MCC from 4 studies (2022-2024) were included for analysis. The median age was 65.5 (39-90) years and majority were male (76%). One of the included studies was phase III trial while three were retrospective studies. ECOG performance status was 0 (41%), 1 (45%), and 2 (14%). 56 patients (70%) had prior ICI exposure with avelumab and pembrolizumab while 24 patients (30%) were ICI naive. Median number of cycles of ipi/nivo was 3.7 (1-4). Median follow-up time was 17 (6.5-37.1) months. The pooled rates of overall response (OR), complete response (CR), and partial response (PR) were 46.8% (95% CI 0.35-0.59, I2= 88%, p < 0.01, n = 78), 14.9% (95% CI 0.06-0.25, I2= 67%, p = 0.03, n = 78), and 26.7% (95% CI 0.16-0.38, I2= 76%, p < 0.01, n = 78), respectively. The pooled rates of stable disease (SD) and progressive disease (PD) were 0% (95% CI 0.00-0.04, I2= 12%, p = 0.33, n = 78) and 49.9% (95% CI 0.38-0.62, I2= 90%, p < 0.01, n = 78), respectively. At 24-months, pooled progression-free survival (PFS) and overall survival (OS) were 27.9% (95% CI 0.18-0.39, I2= 83%, p < 0.01, n = 80) and 57.9% (95% CI 0.45-0.71, I2= 45%, p = 0.16, n = 67), respectively. Pooled mortality rate was 49.1% (95% CI 0.30-0.69, I2= 77%, p = 0.01, n = 30). The pooled rate of grade ≥ 3 adverse events was 32.6% (95% CI 0.22-0.45, I2= 0%, p = 0.97, n = 80) and 13% (n = 10) discontinued treatment due to adverse events. Conclusions: The results of this meta-analysis suggest favorable efficacy of ipi/nivo in metastatic MCC patients with acceptable toxicity profile. However, these results should be interpreted cautiously due to small sample size and retrospective nature of majority of included studies. Future randomized controlled trials are needed to consolidate these findings.