Atezolizumab Plus FOLFIRINOX and Bevacizumab Improves PFS Over Atezolizumab Alone for dMMR/MSI-H Metastatic Colorectal Cancer
Key Clinical Summary
- Population and Design: The phase 3 COMMIT trial enrolled 102 treatment-naive patients with dMMR/MSI-H metastatic colorectal cancer (mCRC), randomized to atezolizumab monotherapy (n = 41) or atezolizumab + modified FOLFIRINOX/bevacizumab (FFX/bev; n = 41) after early closure of the FFX/bev-only arm; median follow-up 3.5 years.
- Efficacy: Median PFS 30.0 vs 4.3 months with combination vs monotherapy (HR 0.439; 95% CI, 0.23 to 0.84; P = 0.0103); ORR 80.6% vs 46% and 12-month DCR 62.9% vs 32.4%, favoring the combination.
- Safety: Grade ≥ 3 adverse events occurred in 34 (combo) vs 18 (mono) patients, including 6 grade 5 events (5 in combo arm), consistent with expected chemotherapy-related toxicity.
- Clinical Relevance: Atezolizumab plus FFX/bev significantly improved PFS and response rates versus immunotherapy alone in first-line dMMR/MSI-H mCRC, supporting combination chemoimmunotherapy as a potential new frontline standard for this biomarker-defined population.
According to results from the phase 3 COMMIT trial, the combination of atezolizumab with FOLFIRINOX and bevacizumab (FFX/bev) significantly prolonged progression-free survival (PFS) compared to atezolizumab monotherapy among patients with treatment-naive mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC).
These results were presented at the ASCO Gastrointestinal Cancers Symposium by Caio Max Sao Pedro Rocha Lima, MD, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.
Researchers conducted a multicenter, randomized, open-label study to determine the safety and efficacy of atezolizumab monotherapy compared with FFX/bev plus atezolizumab. Participants were randomized 1:1:1 to receive atezolizumab alone, FFX/bev alone, or the combination of atezolizumab plus FFX/bev. The primary end point was progression-free survival (PFS) by intent-to-treat. Secondary end points included safety, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS).
Overall, 102 patients with previously untreated dMMR/MSI-H mCRC were included. Following the results of the KEYNOTE-177 trial, the FFX/bev monotherapy arm was closed, and the study continued as a 2-arm comparison between atezolizumab monotherapy (n = 41) and atezolizumab plus FFX/bev (n = 41). The median age was 62 years and 48% were female, and 23% had BRAF V600E mutations.
At a median follow-up of 3.5 years, the median PFS was 30.0 months in the combination arm versus 4.3 months in the monotherapy arm. The combination of atezolizumab plus FFX/bev significantly improved PFS compared to atezolizumab monotherapy, with a hazard ratio (HR) of 0.439 (95% confidence interval [CI], 0.23 to 0.84; P = 0.0103). The ORR was 80.6% among patients treated with atezolizumab plus FFX/bev vs 46% among those treated with atezolizumab monotherapy, and the 12-month DCR was 62.9% vs 32.4%, respectively.
In terms of safety, grade ≥ 3 adverse events occurred among 34 patients in the combination arm compared with 18 in the atezolizumab monotherapy arm. There were 6 grade 5 events in total, 5 of which occurred in the combination arm.
The researchers concluded, “The combination of FFX/bev+atezo led to significantly longer PFS than atezo monotherapy in the first-line setting for dMMR mCRC.”
Source:
Rocha Lima CM, Yothers G, George TJ, et al. Colorectal Cancer Metastatic dMMR Immunotherapy (COMMIT) study: A randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo (FFX/bev) in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC)— NRG-GI004/SWOG-S1610. Presented at 2026 ASCO Genitourinary Cancers Symposium. January 8-10, 2026; San Francisco, CA. Abstract 14.
