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SYSTEMATIC REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1439624
This article is part of the Research Topic Molecular Mechanisms and Targeted Therapies for Colorectal Cancer Vol II View all 5 articles

Evaluation of the Efficacy and Safety of First-and Second-Line Immunotherapy in Patients with Metastatic Colorectal Cancer: A Systematic Review and Network Meta-Analysis Based on Randomized Controlled Trials

Provisionally accepted
Kaiqi Chen Kaiqi Chen 1Wei Chen Wei Chen 2Rui Yue Rui Yue 3Danping Zhu Danping Zhu 4Shikui Cui Shikui Cui 4Xijian Zhang Xijian Zhang 4Zhao Jin Zhao Jin 1*Tong Xiao Tong Xiao 5
  • 1 Chengdu University of Traditional Chinese Medicine, Chengdu, China
  • 2 Department of Pharmacy, Emergency General Hospital, Beijing, China
  • 3 Changhang Hospital, Chongqing, China
  • 4 Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
  • 5 School of Basic Medical Sciences, Capital Medical University, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    Background: Multiple randomized controlled trials (RCTs) for metastatic colorectal cancer (mCRC) patients demonstrated immunotherapy's efficacy using immune checkpoint inhibitors (ICIs). The FDA has approved ICIs for specific mCRC subpopulations. However, direct comparisons of treatment options are limited, leaving the most effective ICI strategies undefined for microsatellite-stable (MSS) and microsatellite instability (MSI) subgroups in first- and second-line therapies. Our study used Bayesian network meta-analysis to identify optimal ICI strategies. Methods: We searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to August 2024, screening 875 studies and ultimately including seven. A systematic review and network meta-analysis were performed. Results: Our analysis of seven RCTs, involving 1,358 mCRC patients, compared first- and second-line immunotherapy regimens. Five initial treatments focused on MSS (three) and MSI (two) patients, and two secondary regimens targeted MSS patients. Among 1051 first-line and 307 second-line patients, ICIs showed varying clinical benefits compared to standard-of-care therapy. Nivolumab with ipilimumab notably improved progression-free survival (PFS) in MSI patients (HR=0.21; 95% CI, 0.13-0.34) with low adverse events (OR=0.33; 95% CI, 0.19-0.56). For MSS patients, Nivolumab plus standard-of-care (SOC) significantly improved PFS (HR=0.74; 95% CI, 0.53-1.02). In second-line MSS therapy, Atezolizumab plus SOC prolonged PFS (HR=0.66; 95% CI, 0.44-0.99). Conclusions: ICIs in first- and second-line mCRC treatments confer substantial benefits. Nivolumab with ipilimumab may be the most efficacious and well-tolerated first-line option for MSI patients, while Nivolumab plus SOC is preferable for MSS patients. For MSS second-line therapy, Atezolizumab plus SOC is effective in prolonging PFS. Other ICI regimens also show promise, informing future treatment guidelines and rationale for ICI selection in mCRC.

    Keywords: Metastatic colorectal cancer, First-and Second-Line, Immunotherapy, efficacy and safety, Network meta-analysis, Microsatellite status

    Received: 28 May 2024; Accepted: 30 Aug 2024.

    Copyright: © 2024 Chen, Chen, Yue, Zhu, Cui, Zhang, Jin and Xiao. 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: Zhao Jin, Chengdu University of Traditional Chinese Medicine, Chengdu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.