Efficacy and safety of nivolumab and ipilimumab in treating metastatic colorectal cancer (mCRC): A systematic review and meta-analysis.

Abstract

e15560 Background: Colorectal cancer is among the top three cancers in the world with approximately a million new cases each year globally. Immunotherapies, such as the combination of nivolumab and ipilimumab, has become a viable treatment option for metastatic colorectal cancer, with efforts being made to broaden the scope of this drug combination on more than one type of population Our study primarily aims to address the efficacy and safety in treating patients with both mismatch repair-deficient, high microsatellite instability (dMMR-MSI-H), mismatch repair-proficient, microsatellite stable (pMMR-MSS) mCRC and various key parameters. Methods: Our systematic review and meta-analysis included 14 clinical studies with 801 participants receiving the dual treatment (PROSPERO ID: CRD42024569856). A comprehensive search was done to include clinical trials that evaluated overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs), as well as studies published between January 2017 and July 2024. Subgroup analysis and meta-regression, which emphasized variations in response across genetic profiles and treatment contexts, were used to address substantial heterogeneity. Quality assessment was done using Cochrane Collaboration RoB v2 tool for RCTs and GRADE assessment for both RCTs and non-RCTs. Results: In a landmark finding, individuals with MSI-H/dMMR demonstrated statistically significant benefit in ORR and PFS over the MSS/pMMR subgroup. In the MSI subgroup for PFS, 0.25 (95% CI: 0.15-0.41, p = 0.006), indicated a remarkable survival of patients using nivolumab and ipilimumab. As a secondary treatment, the combined regimen showed desirable results. The safety profile was incredible and the incidence of major adverse events was lower. A notable improvement in the non-first-line subgroup was seen. Patients who were not RAS+ also exhibited better outcomes in comparison to RAS+. Conclusions: Nivolumab and Ipilimumab as a combination continues to demonstrate success in MSI-H and dMMR populations, our study expands its potential application to MSS mCRC, a subgroup with limited effective treatment options. The favorable safety profile further supports its feasibility as a standard therapeutic option. These results provide a strong rationale for further research to confirm these findings and inform updates to clinical guidelines, potentially broadening the indications for immunotherapy in the treatment of mCRC. This drug combination still remains a concrete treatment for patients with MSI. These findings highlight the potential for expanding immunotherapy applications in diverse mCRC patient populations.