Upfront Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Bevacizumab With or Without Atezolizumab for Patients With Metastatic Colorectal Cancer: Updated and Overall Survival Results of the ATEZOTRIBE Study

J Clin Oncol. 2024 Aug 1;42(22):2637-2644. doi: 10.1200/JCO.23.02728. Epub 2024 Jun 12.

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 4-year results of the phase II randomized AtezoTRIBE study. Eligible patients with metastatic colorectal cancer (mCRC) received first-line fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (control group, n = 73) or FOLFOXIRI/bevacizumab plus atezolizumab (experimental group, n = 145). We present overall survival (OS) and updated outcomes according to tumor immune-related biomarkers, both in the intention-to-treat (ITT) population and the cohort of patients with proficient mismatch repair (pMMR) tumors. Median follow-up was 45.2 months (IQR, 42.6-49.2). In the ITT population, median OS was 33.0 and 27.2 months for experimental and control groups, respectively (hazard ratio [HR], 0.78 [80% CI, 0.61 to 0.98]; P = .084). An interaction effect between Immunoscore Immune-Checkpoint (IC) and treatment arm was observed (Pint, .089), with higher benefit from atezolizumab in the Immunoscore IC-high group. In the pMMR cohort (N = 202), median OS was 30.8 and 29.2 months for experimental and control groups, respectively (HR, 0.80 [80% CI, 0.63 to 1.02]; P = .117). Interactions between treatment group and tumor mutational burden (TMB) and Immunoscore IC were reported (Pint, .043 and .092, respectively), with patients bearing TMB-high and Immunoscore IC-high tumors deriving higher benefit from the addition of atezolizumab. First-line FOLFOXIRI/bevacizumab plus atezolizumab improves OS in patients with mCRC. 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.

Trial registration: ClinicalTrials.gov NCT03721653.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / therapeutic use
  • Camptothecin / analogs & derivatives
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / mortality
  • Colorectal Neoplasms* / pathology
  • Female
  • Fluorouracil* / administration & dosage
  • Fluorouracil* / therapeutic use
  • Humans
  • Irinotecan* / administration & dosage
  • Irinotecan* / therapeutic use
  • Leucovorin* / administration & dosage
  • Leucovorin* / therapeutic use
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / therapeutic use

Substances

  • atezolizumab
  • Leucovorin
  • Bevacizumab
  • Fluorouracil
  • Antibodies, Monoclonal, Humanized
  • Irinotecan
  • Oxaliplatin
  • Organoplatinum Compounds
  • Camptothecin

Supplementary concepts

  • FOLFOXIRI protocol

Associated data

  • ClinicalTrials.gov/NCT03721653