New Protocol: Atezolizumab with FOLFOX and Bevacizumab for Metastatic MSI-H Colorectal Cancer

In this randomized phase 3 study, mFOLFOX6/bevacizumab/atezolizumab significantly improved progression-free survival compared with atezolizumab alone in patients with deficient DNA mismatch repair metastatic colorectal cancer. The combination therapy achieved a higher objective response rate and disease control rate at 12 months, although there was no difference in overall survival. The safety profile of the combination was consistent with the known toxicities of chemotherapy and anti-VEGF therapy, with a higher incidence of Grade 3 or higher adverse events compared to monotherapy.

Study

Randomized, open-label, multicenter, phase 3 study [COMMIT, NCT02997228]

First-line dMMR/MSI-H metastatic colorectal cancer

mFOLFOX6/bevacizumab/atezolizumab (n=41) vs atezolizumab (n=41)

Efficacy

ORR: 86.1% vs 46.0% (FOLFOX/bev/atezo vs. atezo)

CR: 36.1% vs. 18.9%

mPFS: 24.5 mos vs 5.3 mos (HR 0.42 [0.22-0.80])

12-month PFS: 66.7% vs 35.1%

24-month PFS: 53.7% vs 31.6%

12-month DCR: 64.7% vs 32.4%

mOS: Not reached vs Not reached (HR 1.04 [0.47-2.28])

Safety

Grade >=3 AE: overall (82.9% vs 43.9%), neutropenia (26.8% vs None), hypertension (19.5% vs 2.4%), sepsis (9.7% vs None), mucositis oral (9.8% vs 2.4%), fatigue (4.9% vs 2.4%), maculopapular rash (2.4% vs 4.9%), colonic perforation (2.4% vs None), cardiac arrest (2.4% vs None)

Grade 5 AE: 4 vs 1