Dr. Ahn on the Role of Checkpoint Inhibitors in NTRK Fusion+ MSI-H CRC

Daniel H. Ahn, DO, an oncologist, internist, and assistant professor of medicine at Mayo Clinic, discusses the role of checkpoint inhibitor therapy in patients with microsatellite instability–high (MSI-H) colorectal cancer (CRC) who harbor an NTRK fusion.

The utility of dual checkpoint inhibitor therapy with an anti–CTLA-4 monoclonal antibody is not well defined in patients with MSI-H CRC who harbor an NTRK fusion, explains Ahn. Ongoing phase 3 trials are attempting to parse out the role of this combination in this patient population.

Currently, Ahn’s recommends checkpoint inhibitor monotherapy with pembrolizumab (Keytruda) or nivolumab (Opdivo) for these patients. Pembrolizumab demonstrated a median progression-free survivals of 16.5 months as up-front therapy in patients with MSI-H metastatic CRC in the phase 3 KEYNOTE-177 study. and median overall survival that has not been reached, Ahn explains. 

Although chemotherapy can be an effective option in this setting, checkpoint inhibitors are associated with a higher response rate of approximately 50%, says Ahn.

If a patient progresses on a checkpoint inhibitor, the addition of a CTLA-4 inhibitor may be considered, Ahn explains. Additionally, NTRK inhibitors, such as larotrectinib (Vitrakvi) or entrectinib (Rozlytrek), may be utilized to target NTRK fusion proteins, concludes Ahn.