Atezolizumab Combo Improves Survival in Metastatic CRC

"AtezoTRIBE provided preliminary evidence of efficacy of an upfront first-generation [immune checkpoint inhibitor]–based therapeutic strategy in pMMR [metastatic] CRC, and translational analyses identified a subgroup of interest for the further development of this treatment approach,” according to the authors of the study.

Overall survival (OS) was improved when patients with metastatic colorectal cancer (CRC) were treated with atezolizumab (Tecentriq) plus bevacizumab (Avastin) and fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI), according to results from the phase 2 AtezoTRIBE trial (NCT03721653) published in the Journal of Clinical Oncology.

The comparator arm assessed bevacizumab plus FOLFOXIRI. The OS in the triplet arm across the intent-to-treat (ITT) population was 33.0 months vs 27.2 months in the control arm (HR, 0.78; 80% CI, 0.61-0.98; P = .084). Patients with mismatch repair proficient (pMMR) tumors were also assessed and showed a median OS of 30.8 months vs 29.2 months (HR, 0.80; 80% CI, 0.63-1.02; P = .117).

In the pMMR cohort subgroup analyses, the tumor mutational burden (TMB; P = .043) and Immunoscore immune checkpoint (IC) status (P = .092) were associated with a differential OS benefit from adding atezolizumab.

“AtezoTRIBE provided preliminary evidence of efficacy of an upfront first-generation [immune checkpoint inhibitor]–based therapeutic strategy in pMMR [metastatic] CRC, and translational analyses identified a subgroup of interest for the further development of this treatment approach,” the authors of the study stated.

The prospective, open-label, investigator-driven, randomized trial was opened at 22 centers in Italy. A total of 218 patients were randomly assigned to either the control group (n = 73) or the experimental group (n = 145). Of those enrolled, 99% were assessed for mismatch repair status, 72% for Immunoscore IC, and 63% for TMB.

Patients were given treatment in eight 14-day cycles followed by fluorouracil and leucovorin plus bevacizumab with or without atezolizumab. This occurred until disease progression.

At the August 31, 2023 data cutoff, the median follow-up was 45.2 months, with 128 deaths and 177 progression-free survival (PFS) events reported.

The median PFS in the ITT population was 13.1 months in the triplet arm and 11.5 months in the doublet arm (HR, 0.72; 80% CI, 0.59-0.88; P = .018). The median PFS for the pMMR group was 13.0 months vs 11.5 months (HR, 0.80; 80% CI, 0.65-0.99; P = .088).

Subgroup analyses for PFS in the ITT population found an interaction between the treatment group and MMR (P = .010), TMB (P = .008), and Immunoscore IC (P = .055). Similar results were observed in the pMMR cohort with TMB (P = .016) and Immunoscore IC (P = .072).

Following previously reported results from this trial, investigators found no differences in the objective response rate (ORR) or safety. Additionally, there were no new fatal treatment-related AEs in either group.

At first disease progression, 170 patients were alive with 53 in the control group and 88 in the experimental group receiving second-line treatment. Additionally, 132 further PFS events occurred, and 27 patients in the control arm and 55 in the experimental arm were given suggested treatment after random assignment.

Patients aged 18 to 75 years old with unresectable previously treated metastatic CRC were eligible for enrollment. Patients 70 years or younger or with an ECOG performance status of 0 to 2 and those aged 71 to 75 with a performance status of 0 were also eligible. Patient stratification occurred by center, ECOG performance score, primary tumor location, and previous adjuvant treatment. Patients were randomly assigned 1:2 to either the control or experimental groups.

The primary end point was PFS. Secondary end points included OS, second PFS, safety, and ORR.

“At an extended follow-up of approximately 4 years, the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab significantly prolongs PFS and OS in patients with mCRC, with no difference in response rate and a manageable safety profile,” the authors concluded.

Reference

Antoniotti C, Rossini D, Pietrantonio F, et al. 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;42(22):2637-2644. doi:10.1200/JCO.23.02728