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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1570457
This article is part of the Research Topic Immune Checkpoints Regulatory Mechanisms and Immunotherapy Strategies in Gastrointestinal Tumors View all 4 articles
Pembrolizumab versus Bevacizumab Plus Modified FOLFOX6 in Metastatic MSI-H/dMMR Colorectal Cancer: A Multicenter Retrospective Study
Provisionally accepted
Jiaqi Chen 1
Weiguang Yu 2* Xiaobo Xia 1 Yang Zhao 1 Qiang Tang 1 Yunxiang Zhang 1 Yijie Zhang 1 Haoyu Zhang 1 Zhong Zhang 1 Xiaoyan Zhang 1
Jiang Hua Lou 1*- 1 Henan Provincial People's Hospital, Zhengzhou, Henan Province, China
- 2 Sun Yat-sen University, Guangzhou, China
Objective: The optimal therapeutic strategy for metastatic microsatellite instabilityhigh/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC) remains uncertain. This multicenter retrospective study compared the efficacy and safety of pembrolizumab monotherapy versus bevacizumab combined with modified FOLFOX6 (mFOLFOX6) in this molecularly defined population.Methods: Consecutive patients with metastatic MSI-H/dMMR CRC treated with pembrolizumab or bevacizumab plus mFOLFOX6 at two tertiary centers (2017)(2018)(2019)(2020)(2021)(2022)(2023)(2024) were analyzed. Dual primary endpoints included overall survival (OS) and progressionfree survival (PFS); secondary endpoints encompassed incidence of grade ≥3 treatmentemergent adverse events (AEs).Results: Among 58 eligible patients (PE: n=30; BF: n=28), the PE cohort demonstrated a significantly higher objective response rate (ORR) compared to the BF cohort (XX% vs XX%, p=0.030) after a median follow-up of 18.0 months (IQR: 1.0-24.0). Survival analyses revealed superior outcomes in the PE cohort, with a median OS of 12.0 months (95% CI: 10.2-14.1) versus 8.8 months (95% CI: 7.1-9.6) in the BF cohort (HR=0.55, 95% CI: 0.29-0.56; p=0.02). Similarly, median PFS was prolonged in the PE cohort (7.0 months, 95% CI: 5.3-9.3) relative to the BF cohort (3.7 months, 95% CI: 2.2-5.4; HR=0.46, 95% CI: 0.24-0.89; p<0.001). No statistically significant intergroup differences were observed in grade ≥3 treatment-emergent AE rates.Pembrolizumab monotherapy significantly improved survival over bevacizumab-based chemotherapy in metastatic MSI-H/dMMR CRC, with a manageable safety profile. These results reinforce PD-1 inhibitors as first-line therapy for this 4 population, while highlighting tumor mutation burden (TMB) and tumor burden as critical biomarkers for personalized strategies.
Keywords: Pembrolizumab, bevacizumab, colorectal cancer, FOLFOX6, overall survival
Received: 03 Feb 2025; Accepted: 19 Mar 2025.
Copyright: © 2025 Chen, Yu, Xia, Zhao, Tang, Zhang, Zhang, Zhang, Zhang, Zhang and Lou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Weiguang Yu, Sun Yat-sen University, Guangzhou, China
Jiang Hua Lou, Henan Provincial People's Hospital, Zhengzhou, 450000, Henan Province, China
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