Work

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

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

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.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1969514