KEY TAKEAWAYS
- The AtezoTRIBE trial is a phase 3 multicentre, open-label, randomized, controlled study in patients with unresectable, previously untreated metastatic colorectal cancer.
- The trial evaluated the benefit of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab regarding progression-free survival.
- Patients were randomly assigned to either the control group, which received FOLFOXIRI plus bevacizumab, or the atezolizumab group.
- At the data cutoff, the median follow-up was 19.9 months, and the median PFS was 13.1 months in the atezolizumab group compared to 11.5 months in the control group.
- The most frequent all-cause grade 3-4 adverse events were neutropenia, diarrhea, and febrile neutropenia.
- Adding atezolizumab to first-line FOLFOXIRI plus bevacizumab was safe and improved PFS in patients with previously untreated mCC.
Previous studies have found no clinical benefit from immune checkpoint inhibitors for patients with metastatic colorectal cancer with either pMMR or microsatellite stable (MSS) tumors. Increasing the immunogenicity of pMMR or MSS tumors appears possible with both bevacizumab and active combination chemotherapy (FOLFOXIRI; fluorouracil, leucovorin, oxaliplatin, and irinotecan). Our study’s primary objective was to collect preliminary data on the efficacy of adding the anti-PD-L1 agent atezolizumab to first-line FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer.
Patients with histologically confirmed, unresectable, previously untreated metastatic colorectal cancer and adequate organ function were recruited from 22 oncology centers in Italy. They participated in the AtezoTRIBE, a multicenter, open-label, randomized, controlled phase 2 study. Center, Eastern Cooperative Oncology Group performance status, primary tumor site, and prior adjuvant therapy were used to divide patients into groups. Patients were randomly assigned (1:2) using a masked web-based allocation procedure to one of two treatment groups: the control group received first-line FOLFOXIRI (intravenous 165 mg/m2 irinotecan, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, and 3200 mg/m2 fluorouracil as a 48 h infusion) plus bevacizumab (5 mg/kg intravenous (840 mg intravenously). Maintenance treatment consisted of fluorouracil and leucovorin plus bevacizumab with or without atezolizumab, based on the randomized group, until disease progression, unacceptable adverse events, or withdrawal of consent. Each cycle lasted 14 days. Analysis was performed according to the intention-to-treat principle, and progression-free survival (PFS) was the primary endpoint. Patients who participated in the study and received at least one treatment dose were monitored for safety.
A total of 218 patients were randomly assigned and treated between November 30, 2018, and February 26, 2020. (73 in the control group and 145 in the atezolizumab group). The median follow-up time was 19.9 months (IQR 17.3-23.9) as of the data cutoff date of August 1, 2021. The atezolizumab group had a median PFS of 13.1 months (80% CI 12.5-23.8) compared to 11.5 months (10.0-12.6) in the control group (hazard ratio [HR] 0.69% [80% CI 0.56-0.85]; p=0.012; adjusted HR 0.69% [80% CI 0.56-0.87]; log-rank test p=0.018). Neutropenia (59 [42%] of 142 patients in the atezolizumab group vs. 26 [36%] of 72 patients in the control group), diarrhea (21 [15%] vs. nine [13%]), and febrile neutropenia (14 [10%] vs. seven [10%]) were the most common all-cause grade 3-4 adverse events. In the atezolizumab group, 27 percent of patients experienced serious adverse events; in the control group, 26 percent experienced serious adverse events. Two deaths in the atezolizumab group (1%) were attributed to the treatment (acute myocardial infarction and bronchopulmonary hemorrhage), while no such deaths were reported in the placebo group. Patients with untreated metastatic colorectal cancer benefited from adding atezolizumab to first-line FOLFOXIRI plus bevacizumab.
Source: https://pubmed.ncbi.nlm.nih.gov/35636444/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03721653
Antoniotti C, Rossini D, Pietrantonio F, Catteau A, Salvatore L, Lonardi S, Boquet I, Tamberi S, Marmorino F, Moretto R, Ambrosini M, Tamburini E, Tortora G, Passardi A, Bergamo F, Kassambara A, Sbarrato T, Morano F, Ritorto G, Borelli B, Boccaccino A, Conca V, Giordano M, Ugolini C, Fieschi J, Papadopulos A, Massoué C, Aprile G, Antonuzzo L, Gelsomino F, Martinelli E, Pella N, Masi G, Fontanini G, Boni L, Galon J, Cremolini C; GONO Foundation Investigators. Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomized, controlled, phase 2 trial. Lancet Oncol. 2022 Jul;23(7):876-887. doi: 10.1016/S1470-2045(22)00274-1. Epub 2022 May 27. PMID: 35636444.
