- This review summarizes data on anti-programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) monoclonal antibodies in patients with metastatic colorectal cancer (mCRC).
- Immune checkpoint inhibitors have shown efficacy in deficient mismatch repair (dMMR) or highly microsatellite instable (MSI-H) CRC; but not in those with proficient MMR (pMMR) or microsatellite stable (MSS) tumors.
- The prevalence of dMMR is higher in stage II-III vs IV mCRC.
- In dMMR tumors, high PD-1/PD-L1 expression is associated with superior recurrence-free survival.
- CRC is a genetically heterogeneous disease; 4 Consensus Molecular Subtypes (CMSs) are characterized by relevant differences in tumor microenvironment.
- CMS 1/4 show intense immune infiltration, whereas CMS 2/3 lack immune activation.
- US Food and Drug Administration approved pembrolizumab, nivolumab, and nivolumab+ipilimumab in patients with MSI-H mCRC who progressed on fluoropyrimidines+irinotecan or oxaliplatin, based on data from KEYNOTE-016 and CheckMate-142 trials.
- The relevant clinical benefit is, however, limited to only approximately 4% of mCRC cases.
- Anti-PD-1 therapy has shown no benefit in patients with pMMR mCRC; therefore, novel therapeutic strategies are urgently needed in these tumors.
- Combining chemotherapy, molecular targeted therapies, and radiotherapy with immune checkpoint inhibitors may overcome the primary resistance to immunotherapy of MSS CRC.