Pembrolizumab versus bevacizumab plus modified FOLFOX6 in metastatic MSI-H/dMMR colorectal cancer: a multicenter retrospective study with CT evaluation

• DOI: 10.3389/fonc.2025.1570457
• Publication Date: 2025-04-04T10:20:17Z
• Authors: Jiaqi Chen; Weiguang Yu; Xiaobo Xia; Yang Zhao; Qiang Tang; Yunxiang Zhang; Yijie Zhang; Haoyu Zhang; Zhong Zhang; Xiaoyan Zhang; Jianghua Lou
• Keywords: Clinical endpoint; Progression-free survival

Objective The optimal therapeutic strategy for metastatic microsatellite instability-high/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 MSI-H/dMMR CRC treated or plus mFOLFOX6 at two tertiary centers (2017–2024) were analyzed. Dual primary endpoints included overall survival (OS) progression-free (PFS); secondary encompassed incidence grade ≥3 treatment-emergent adverse events (AEs). Results Among 58 eligible (PE: n=30; BF: n=28), PE cohort demonstrated a significantly higher objective response rate (ORR) to BF (XX% vs XX%, p=0.030) after median follow-up 18.0 months (IQR: 1.0–24.0). Survival analyses revealed superior outcomes cohort, OS 12.0 (95% CI: 10.2–14.1) 8.8 7.1–9.6) (HR=0.55, 95% 0.29–0.56; p=0.02). Similarly, PFS was prolonged (7.0 months, 5.3–9.3) relative (3.7 2.2–5.4; HR=0.46, 0.24–0.89; p<0.001). No statistically significant intergroup differences observed AE rates. Conclusion Pembrolizumab improved over bevacizumab-based chemotherapy CRC, manageable profile. These results reinforce PD-1 inhibitors as first-line therapy population, while highlighting tumor mutation burden (TMB) critical biomarkers personalized strategies.