Multicenter phase 3 trial of first-line atezolizumab with or without mFOLFOX6-bevacizumab for dMMR/MSI-H mCRC

Prof. Caio Max Sao Pedro Rocha Lima

Nearly half of the patients with mismatch repair-deficient/ microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) receiving first-line single-agent PD-1 therapy will progress within 12 months. Preclinical studies in CRC and data from other cancers suggest that VEGF inhibition and chemotherapy can synergize with PD-L1 inhibition. The multicenter phase 3 COMMIT trial in the USA compared three first-line treatments for dMMR/MSI-H mCRC: mFOLFOX6-bevacizumab (FFX-bev), atezolizumab monotherapy (atezo), and FFX/bev/atezo. The primary endpoint was progression-free survival (PFS). Because of KEYNOTE-177 results, the FFX-bev arm was closed after 20 patients were enrolled. The atezo monotherapy and the FFX/bev/atezo arms enrolled 41 patients each. At a median follow-up of 46 months for the two arms, PFS of FFX/bev/atezo was superior to that of atezo (HR 0.349; p=0.0103); the objective response rate was 86.1% versus 46%, and the disease control rate at 12 months was 64.7% versus 32.4%, respectively. Grade 3 or higher adverse events of any attribution occurred in 34 patients in the combination arm and 18 patients in the atezo monotherapy arm. The authors conclude that the combination of FFX/bev plus atezo led to significantly longer PFS compared with atezo monotherapy in the first-line treatment of dMMR/MSI-H mCRC.