Metastatic Colorectal Cancer: Addition of Atezolizumab to First-Line FOLFOXIRI/Bevacizumab

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As reported in the Journal of Clinical Oncology by Antoniotti et al, 4-year follow-up of the Italian phase II ATEZOTRIBE trial showed a numeric benefit in overall survival with the addition of atezolizumab to first-line FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) and bevacizumab in patients with metastatic colorectal cancer. In addition, patient subgroups benefitting from atezolizumab were identified.

Study Details

In the multicenter open-label trial, 218 patients were randomly assigned 2:1 to receive atezolizumab plus FOLFOXIRI/bevacizumab (n = 145) or FOLFOXIRI/bevacizumab (n = 73). Overall, 215 patients (99%), 157 patients (72%), and 138 patients (63%) were assessed for mismatch repair (MMR), Immunoscore Immune Checkpoint (IC), and tumor mutational burden (TMB) status, respectively. For the atezolizumab group and the control group, proficient MMR (pMMR) status was present in 134 patients (94.4%) and 68 patients (93.2%), respectively; Immunoscore-IC score was high in 32 (32.0%) and 18 (31.6%), and TMB was high in 11 (12.2%) and 5 (10.4%).

Key Findings

Median follow-up was 45.2 months (interquartile range = 42.6–49.2 months). Median overall survival in the intention-to-treat population was 33.0 months in the atezolizumab group vs 27.2 months in the control group (hazard ratio [HR] = 0.78, 80% CI = 0.61–0.98, P = .084). An interaction between treatment group and Immunoscore-IC was observed (P for interaction = .089), with greater benefit from atezolizumab found in the Immunoscore IC–high group (HR = 0.41, 95% CI = 0.18–0.95).

Among 202 patients with pMMR status, median overall survival was 30.8 months vs 29.2 months (HR = 0.80, 80% CI = 0.63–1.02, P = .117). Interactions between treatment group and TMB (P for interaction = .043) and Immunoscore-IC (P for interaction = .092) were identified, with greater benefit of atezolizumab found in patients with TMB-high (HR = 0.03, 95% CI = 0.00–0.34) and Immunoscore IC–high tumors (HR = 0.42, 95% CI = 0.18–0.99).

The investigators concluded, “First-line FOLFOXIRI/bevacizumab plus atezolizumab improves overall survival in patients with metastatic colorectal cancer. In the pMMR group, patients with Immunoscore IC–high and/or TMB-high tumors are identified as a subgroup of interest to further develop this treatment.”

Chiara Cremolini, MD, PhD, of the Department of Medical Oncology, University Hospital of Pisa, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the GONO Foundation, ARCO Foundation, F. Hoffmann-La Roche, and Roche. For full disclosures of the study authors, visit

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