CTLA-4 Blockade in the Treatment of Colorectal Cancer with Microsatellite Instability

Colorectal cancer is one of the most common tumors worldwide, with around 10-15% of cases being related to microsatellite instability, which is in turn responsible for a high neoantigen load and tumor mutational burden. These characteristics are responsible for the poor response of these tumors to chemotherapy, highlighting the need for a different approach in the treatment of patients with microsatellite-unstable colorectal cancer. Immunotherapy was proven important in the treatment of these patients, with immune checkpoint inhibition such as CTLA-4 blockade being one of the most promising targets so far. Evidence Acquisition: A PubMed search was done on February 2021 where the used query obtained a total of 33 articles. After implementing the inclusion and exclusion criteria, a total of 21 articles were filtered and used in this narrative review. Results: Several studies with microsatellite-unstable colorectal tumors have been done in order to evaluate the advantages and adverse events of CTLA-4 blockade in these patients. Studies show a benefit regarding the progression-free survival, overall survival, and overall response rates in patients receiving ipilimumab (anti-CTLA-4) when compared to those who weren’t. Besides, the main adverse events were manageable and were more tolerable than those observed with chemotherapy. Nonetheless, unlike PD-1 blockade, anti-CTLA-4 drugs are currently only approved for use as part of combination therapy in microsatellite-unstable colorectal cancer, still awaiting approval as monotherapy. Conclusion: Microsatellite-unstable colorectal tumors deserve a different treatment path as their characteristics make them poor responders to chemotherapy. At the same time, these tumors are excellent candidates for immunotherapy, particularly with CTLA-4 inhibitors.