Efficacy and safety of immune checkpoint inhibitors in patients with unresectable metastatic colon cancer with microsatellite instability high or mismatch repair deficiency: A systematic review and meta-analysis.

Abstract

e15543 Background: Metastatic colon cancer (mCRC) characterized by microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) status in shows high mutational burdens making it highly responsive and susceptible to immune checkpoint blockade. We conducted a proportional systematic review and meta-analysis to evaluate the clinical efficacy and safety profile of ICIs in patients with MSI-H/dMMR mCRC based on data from previous clinical trials. Methods: A systematic literature review was conducted by searching PubMed, EMBASE, Cochrane Library for RCTs and single arm studies investigating ICIs in patients with unresectable MSI-H/dMMR mCRC published till January 2025.The intervention was either pembrolizumab or combination Ipilimumab plus Nivolumab. The primary endpoints were progression-free survival (PFS) at 12 and 24 months. Secondary endpoints included the incidence of adverse events and a subgroup analysis for combination therapy with Ipilimumab and Nivolumab. Proportions with corresponding 95% confidence intervals (CIs) were calculated using a random-effects model.Heterogeneity was assessed using the I² statistic. Results: A total of 3 studies were included in our analysis encompassing a total of 655 patients.55% of the patients had PFS at 12 months [0.55 (0.46;0.63), p = 0.08]. 40% of the patients had progression free survival(PFS) at 24 months [0.40 (0.30;0.50) P0.02]. 44% of the patients experienced adverse events[ 0.44 (0.21;0.69) p < 0.01].53% of the patients in the Ipilimumab plus Nivolumab Subgroup had PFS at 12 months [0.53 (0.39;0.67), p = 0.08]. 43% of the patients in the Ipilimumab plus Nivolumab subgroup had PFS at 24 months [0.43 (0.24;0.65), p < 0.01]. Conclusions: This SRMA shows significant improvement in (PFS) at 12 and 24 months, particularly with combination therapy of Ipilimumab and Nivolumab. Additionally,adverse events were reduced highlighting a manageable safety profile. Further studies with longer follow up are needed to validate these findings and optimize treatment strategies. Baseline characteristics of included studies. References Year of study Trial phase Cancer type Study design Intervention Dose Number of patients Median Age (years) Andre et al. 2024 III Metastatic MSI-H _dMMR Colorectal cancer RCT Ipilimumab plus Nivolumab 240mg Nivoluman and 1mg/kg ipilimumab 303 62 Lenz et al. 2021 II Metastatic MSI-H _dMMR Colorectal cancer Single arm trial Nivolumab plus low dose ipilimumab 3mg/kg Nivolumab and 1mg/kg ipilimumab 45 66 Andre et al. 2020 III Metastatic MSI-H _dMMR Colorectal cancer RCT Pembrolizumab 200mg 307 63 MSI-H : Microsatellite instability High. dMMR : Mismatch repair deficient. RCT : Randomised controlled trial. ICI : Immune checkpoint inhibitors. SRMA: Systematic Review and meta-analysis.