COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer
Mené sur 102 patients atteints d'un cancer colorectal de stade métastatique et présentant une haute instabilité des microsatellites ou une déficience du système de réparation MMR (durée médiane de suivi : 46 mois), cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement de première ligne par atézolizumab, seul ou avec une chimiothérapie de type mFOLFOX6 et du bévacizumab
PURPOSE: Immunotherapy for frontline mismatch repair–deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective; however, nearly half of the patients treated with single-agent PD-1 therapy will progress within 12 months. Preclinical studies in CRC and clinical data from other cancers suggest that vascular endothelial growth factor inhibition and chemotherapy can synergize with PD-L1 inhibition.
METHODS: The NRG-GI004/SWOG-S1610 (COMMIT) three-arm prospective phase III open-label trial randomly assigned first-line dMMR/MSI-H mCRC patients (1:1:1) to either: mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m², and 46-hour infusional 5-FU 2,400 mg/m²)/bevacizumab (FFX/bev), or atezolizumab (atezo) monotherapy (840 mg IV once every 2 weeks), or the combination of FFX/bev/atezo. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Because of KEYNOTE 177 results, the FFX/bev arm was closed after 20 patients were enrolled. The study continued with atezo alone versus FFX/bev/atezo, with a revised sample size of 100 patients in the two remaining arms (120 patients across all three arms).
RESULTS: From November 2017 to March 2025, a total of 102 patients were enrolled in the three arms: FFX/bev: n = 20, atezo: n = 41, and FFX/bev/atezo: n = 41. At a median follow-up of 46 months for the two arms (median age: 63.3 years; 47.6% female; 23.2% BRAF V600E mutated), PFS of FFX/bev/atezo was superior to that of atezo (hazard ratio [HR], 0.439 [95% CI, 0.23 to 0.84]; P = .0103) and below the critical value of 0.0152. The objective response rate was 86.1% versus 46%, and the disease control rate at 12 months was 64.7% versus 32.4% in the FFX/bev/atezo arm compared with the atezo-only arm, respectively. Grade 3 or higher adverse events of any attribution occurred in 52 patients (atezo: 18; combination arm: 34).
CONCLUSION: 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.
Journal of Clinical Oncology , résumé, 2026