Intrinsic resistance and efficacy of immunotherapy in microsatellite instability-high colorectal cancer: A systematic review and meta-analysis

Authors

  • Ren Wang Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
  • Jie Lian Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
  • Xin Wang Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
  • Xiangyi Pang Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
  • Benjie Xu Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
  • Shuli Tang Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
  • Jiayue Shao Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
  • Haibo Lu Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China

DOI:

https://doi.org/10.17305/bjbms.2022.8286

Keywords:

Colorectal cancer, MSI-H, intrinsic resistance, efficacy, immunotherapy

Abstract

Some patients with microsatellite instability-high colorectal cancer (MSI-H CRC) have shown a poor response to immunotherapy in clinical trials. We investigated the intrinsic resistance to and efficacy of immunotherapy in patients with MSI-H CRC. The PubMed and Web of Science databases were searched using keywords such as “colorectal cancer,” “immunotherapy,” and “clinical experiment.” Random-effects models were used to generate the combined complete response, partial response, stable disease, progressive disease, objective response rate (ORR), disease control rate (DCR), and incidence of adverse events. We then performed a subgroup analysis based on the ORR and incidence of intrinsic resistance. The meta-analysis included seven clinical trials. The incidences of complete response, partial response, stable disease, and progressive disease summarized by the random-effects model were 8%, 37%, 26%, and 25%, respectively. The ORR and DCR were 45% and 71%, respectively. The ORRs of programmed cell death protein 1 inhibitor (anti-PD-1), programmed death ligand 1 inhibitor (anti-PD-L1), and anti-PD-1 combined with cytotoxic T lymphocyte-associated antigen 4 inhibitor (anti-CTLA-4) immunotherapy were 38%, 54%, and 57%, respectively. The ORR of immune checkpoint inhibitors for first- and third-line therapy was 56% and 32%, respectively. Dual-drug immunotherapy significantly reduced the incidence of intrinsic resistance to immunotherapy (12% vs 31%). The incidences of intrinsic resistance to first-line therapy and second-line and later therapy were 29% and 26%, respectively. Approximately 25% of patients with MSI-H CRC had intrinsic resistance to immunotherapy. Anti-PD-1 combined with anti-CTLA-4 significantly increased the ORR, thereby reducing the incidence of intrinsic resistance. Moving immunotherapy into earlier lines of therapy, although not reducing the incidence of intrinsic resistance, can improve the ORR in patients with MSI-H CRC.

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Author Biography

  • Ren Wang, Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China

     

     

Intrinsic resistance and efficacy of immunotherapy in microsatellite instability-high colorectal cancer: A systematic review and meta-analysis

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Additional Files

Published

16-03-2023

How to Cite

1.
Intrinsic resistance and efficacy of immunotherapy in microsatellite instability-high colorectal cancer: A systematic review and meta-analysis. Biomol Biomed [Internet]. 2023 Mar. 16 [cited 2024 May 20];23(2):198–208. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/9073