Immune Checkpoint Inhibitors for Metastatic Colorectal Cancer: A Systematic Review

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Colorectal cancer (CRC) presents a significant global health challenge.
• Immunotherapy, particularly checkpoint inhibitors, has emerged as a key therapeutic strategy for advanced CRC.
• Understanding the efficacy of these agents in different CRC subtypes is crucial.

Purpose of the Study:

• To systematically review the clinical evidence on checkpoint inhibitors in metastatic colorectal cancer (mCRC).
• To evaluate the efficacy and safety of immunotherapy in MSI and MSS mCRC subtypes.
• To assess the role of combination strategies in mCRC treatment.

Main Methods:

• A systematic review of clinical trials and randomized controlled trials (RCTs) published between January 2019 and January 2025.
• Searches were conducted across Medline, Web of Science, and Cochrane databases.
• Primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).

Main Results:

• Checkpoint inhibitors demonstrated significant efficacy in microsatellite instability (MSI) metastatic colorectal cancer (mCRC).
• Immunotherapy was less effective in microsatellite stability (MSS) mCRC, with combination strategies yielding mixed outcomes.
• Grade ≥ 3 treatment-related adverse events (TRAEs) were frequently observed with combination regimens.

Conclusions:

• Immunotherapy has transformed the treatment landscape for MSI mCRC.
• Current immunotherapy approaches for MSS CRC remain unconvincing.
• Combination strategies and novel agents show promise but require further investigation for efficacy and safety.