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

作者：Elena Élez, Salvatore Siena, A. Sartore-Bianchi, Javier Ros, Fortunato Ciardello, Erika Martinelli, Neeltje Steeghs, Sanne C.F.A. Huijberts, Andrés Cervantes, Susana Roselló, Sabine Tejpar, B Wilmsen, Ramón Salazar, Cristina Santos, Gaetan de Schaetzen, Susana Muñoz, René Bernards, Vı́ctor Moreno, E García-Galera, Ramón Alemany, Alena Gros, A. Bardelli, Sabrina Arena, Adriano Piris, Édison Francisco Viveros Chavarría, Rodrigo Dienstmann, Josep Tabernero · 发表于：ESMO Open · 年份：2025 · DOI：10.1016/j.esmoop.2025.105892 · 被引用次数：2 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Immunotherapy and Biomarkers、Gastric Cancer Management and Outcomes

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 w...