Dr. Andre on the Rationale for the KEYNOTE-177 Trial in mCRC

Thierry Andre, MD, professor of medical oncology, University Pierre et Marie Curie (UMPC), and Head of the Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris, discusses the rationale for the phase 3 KEYNOTE-177 trial in metastatic colorectal cancer (mCRC).

The standard treatment for patients with mCRC is chemotherapy plus cetuximab (Erbitux), panitumumab (Vectibix), or bevacizumab (Avastin), says Andre. However, patients with microsatellite instability—high (MSI-H) mCRC receive limited benefit from this regimen in terms of progression-free survival and response rates compared with patients with microsatellite stable disease.

As such, KEYNOTE-177 randomized patients with MSI-H/mismatch repair deficient mCRC to pembrolizumab (Keytruda) versus standard of care chemotherapy with or without bevacizumab or cetuximab as first-line therapy.

Phase 2 data suggested that previously treated patients with MSI-H tumors can derive survival benefit from pembrolizumab, explains Andre.

Additionally, MSI-H mCRC is associated with a high tumor burden and neoantigen load and therefore is thought to be responsive to immunotherapy, concludes Andre.