Efficacy and safety of atezolizumab plus bevacizumab in MSI-like metastatic colorectal cancer: a multicenter, single-arm, phase II, open-label clinical trial

ESMO Open. 2025 Dec 2;10(12):105892. doi: 10.1016/j.esmoop.2025.105892. Online ahead of print.

ABSTRACT

BACKGROUND: The use of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC) remains limited to tumors harboring microsatellite instability (MSI); however, a subset of microsatellite stable (MSS) tumors features an MSI-like phenotype that could predict responses to ICIs combined with anti-angiogenesis agents.

PATIENTS AND METHODS: In this single-arm phase II trial, 45 mCRC patients with a positive tumoral MSI-like gene expression signature (GES) progressing to at least one chemotherapy regimen were recruited from seven European sites within the MoTriColor framework. Of these, 24 and 21 were MSI and MSS, respectively, by standard assays. Patients received intravenous atezolizumab (1200 mg) plus bevacizumab (7.5 mg/kg) infusions in 21-day cycles until progression, unacceptable toxicity, or consent withdrawal. The main outcome measure was the objective response rate (ORR, RECIST 1.1).

RESULTS: The median (interquartile range) age of participants was 63 (58-73) years, 51.1% were male, 60.0% had right-sided tumors, and 31.1% had liver metastases. The ORR in the whole (MSI-like) sample was 38.6% [95% confidence interval (CI) 24.4% to 54.5%]. Among patients with MSI and MSS tumors, the ORR was 65.2% (95% CI 42.7% to 83.6%) and 9.5% (95% CI 1.2% to 30.4%), respectively. In the MSS subgroup without liver metastasis, the ORR was 15.4% (95% CI 1.9% to 45.4%). Overall median progression-free survival was 6.4 (95% CI 4.1-21.2) months (23.2 and 4.0 months in patients with MSI and MSS tumors, respectively). Grade ≥3 adverse events related to atezolizumab and bevacizumab occurred in 5 (11.1%) and 10 patients (22.2%), respectively. There were two grade 5 adverse events, of which one (colonic hemorrhage) was related to bevacizumab.

CONCLUSIONS: MSI-like GES does not identify a population with higher sensitivity to immune checkpoint plus angiogenesis inhibition. However, responses are promising in patients with MSI tumors and, to a lesser extent, in patients without liver metastasis regardless of MSI status.

PMID:41337858 | DOI:10.1016/j.esmoop.2025.105892