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Peer-reviewedCC BY 4.0Frontiers in Oncology

PD-1/PD-L1 inhibitors in the treatment of pMMR mCRC: a meta-analysis based on randomized controlled trials

  • Sumin Lv1
  • Chaoyue Ma2
  • Zeqi Tang2
  • Xinyan Zhang2
  • Wen Shi2
  • Shiyan Zhang3
  • Minyuan Ni3
  • Lihu Gu1
  • Bangsheng Chen4
4 affiliations
  1. 1Department of General Surgery, Ningbo No.2 Hospital, Wenzhou Medical University
  2. 2The Fifth Clinical Medical College of Zhejiang Chinese Medical University
  3. 3The Second Clinical Medical College of Zhejiang Chinese Medical University
  4. 4Emergency Medical Center, Ningbo Hospital of Integrated Traditional Chinese and Western Medicine
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Abstract

Background: The clinical efficacy of PD-1/PD-L1 inhibitors combined with chemotherapy (± targeted agents) in patients with proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) remains unclear. This study systematically evaluated the efficacy of this regimen.

Methods: We searched PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) published up to May 2026. The primary outcomes were progression-free survival (PFS) and overall survival (OS); effect sizes were estimated as hazard ratios (HRs) and 95% confidence intervals (95%CIs).

Results: Six RCTs comprising 1,165 participants were included. The addition of PD-1/PD-L1 inhibitors to chemotherapy, with or without anti-VEGF agents, was associated with prolonged PFS (HR = 0.84, 95%CI [0.73, 0.95], P = 0.007) and OS (HR = 0.83, 95%CI [0.73, 0.94], P = 0.004). Subgroup analyses for PFS preliminarily suggested greater benefit in male patients (HR = 0.77, 95%CI [0.64, 0.94], P = 0.010), those with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (HR = 0.73, 95%CI [0.56, 0.95], P = 0.018), those with liver metastases (HR = 0.82, 95%CI [0.68, 0.98], P = 0.027), those without prior adjuvant therapy (HR = 0.81, 95%CI [0.67, 0.98], P = 0.030), those with a PD-L1 combined positive score (CPS) < 1 (HR = 0.53, 95%CI [0.30, 0.95], P = 0.032), those with synchronous metastases (HR = 0.79, 95%CI [0.63, 0.99], P = 0.037), and those with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (HR = 0.49, 95%CI [0.30, 0.80], P=0.005). These subgroup findings are exploratory, and interaction tests were not performed.

Conclusions: PD-1/PD-L1 inhibitors combined with chemotherapy (with or without targeted agents) may improve the prognosis of patients with pMMR mCRC and represent a potential first-line treatment option.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261330186.

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Cite

BibTeXRIS
BibTeX
@article{lv2026pd1pdl1,
  title = {{PD-1/PD-L1 inhibitors in the treatment of pMMR mCRC: a meta-analysis based on randomized controlled trials}},
  author = {Sumin Lv and Chaoyue Ma and Zeqi Tang and Xinyan Zhang and Wen Shi and Shiyan Zhang and Minyuan Ni and Lihu Gu and Bangsheng Chen},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1969514},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1969514/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - PD-1/PD-L1 inhibitors in the treatment of pMMR mCRC: a meta-analysis based on randomized controlled trials
AU  - Sumin Lv
AU  - Chaoyue Ma
AU  - Zeqi Tang
AU  - Xinyan Zhang
AU  - Wen Shi
AU  - Shiyan Zhang
AU  - Minyuan Ni
AU  - Lihu Gu
AU  - Bangsheng Chen
PY  - 2026
DA  - 2026/10/21
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1969514
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1969514/full
AB  - Background: The clinical efficacy of PD-1/PD-L1 inhibitors combined with chemotherapy (± targeted agents) in patients with proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) remains unclear. This study systematically evaluated the efficacy of this regimen.  Methods: We searched PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) published up to May 2026. The primary outcomes were progression-free survival (PFS) and overall survival (OS); effect sizes were estimated as hazard ratios (HRs) and 95% confidence intervals (95%CIs).  Results: Six RCTs comprising 1,165 participants were included. The addition of PD-1/PD-L1 inhibitors to chemotherapy, with or without anti-VEGF agents, was associated with prolonged PFS (HR = 0.84, 95%CI [0.73, 0.95], P = 0.007) and OS (HR = 0.83, 95%CI [0.73, 0.94], P = 0.004). Subgroup analyses for PFS preliminarily suggested greater benefit in male patients (HR = 0.77, 95%CI [0.64, 0.94], P = 0.010), those with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (HR = 0.73, 95%CI [0.56, 0.95], P = 0.018), those with liver metastases (HR = 0.82, 95%CI [0.68, 0.98], P = 0.027), those without prior adjuvant therapy (HR = 0.81, 95%CI [0.67, 0.98], P = 0.030), those with a PD-L1 combined positive score (CPS) < 1 (HR = 0.53, 95%CI [0.30, 0.95], P = 0.032), those with synchronous metastases (HR = 0.79, 95%CI [0.63, 0.99], P = 0.037), and those with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (HR = 0.49, 95%CI [0.30, 0.80], P=0.005). These subgroup findings are exploratory, and interaction tests were not performed.  Conclusions: PD-1/PD-L1 inhibitors combined with chemotherapy (with or without targeted agents) may improve the prognosis of patients with pMMR mCRC and represent a potential first-line treatment option.  Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261330186.
SN  - 2234-943X
ER  -