Systematic review of efficacy of immune checkpoint inhibitors in microsatellite stable colorectal cancer

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflated tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. Systematic review of 53 published studies found that ICI monotherapy or ICI-ICI combinations for MSS CRC resulted in ORRs below 10% in most studies. ICIs in combination with tyrosine kinase inhibitors resulted in ORRs ranging from 10% to 40% and indicated higher benefits, particularly among patients without active liver metastases. The combinations of ICIs with anti-VEGF agents showed modest ORRs. Well-definied biomarkers to identify patients with probability of benefit are yet to be delineated. Combinations of ICIs with BRAF inhibitors showed promising responses in molecularly defined subgroups. The authors conclude that while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes.