ArticleWorld journal of clinical oncology2025
Adding programmed death 1/programmed death ligand 1 inhibitors to first-line standard-of-care therapy for metastatic colorectal cancer: A meta-analysis.
Article in World journal of clinical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIn recent years, emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand (PD-1/L1) inhibitors are incorporated into first-line standard-of-care (SOC) therapy for metastatic colorectal cancer (mCRC). However, data obtained from these trials demonstrated conflicting evidence concerning survival benefits and clinical outcomes.
aimTo evaluate the therapeutic impact and safety parameters of combining PD-1/L1 inhibitors with SOC protocols as first-line treatment for mCRC.
methodsFour biomedical databases (PubMed, Embase, Cochrane Library, Web of Science) were systematically interrogated to identify eligible studies published up to October 12, 2024. The analysis focused on evaluating the primary outcome of overall survival (OS) in the mCRC population with secondary outcomes of progression-free survival (PFS), overall response rate (ORR), and incidence rate of grade ≥ 3 adverse events. Additionally, we performed exploratory analyses in the microsatellite stable/mismatch repair-proficient (MSS/pMMR) subpopulation, based on a subset of the included studies. Subgroup analyses according to PD-1/L1 inhibitor use were conducted in both the overall population and the MSS/pMMR subgroup.
resultsThis pooled analysis incorporated six randomized controlled trials involving 675 patients with mCRC receiving first-line therapy. The combination of PD-1/L1 inhibitors with SOC regimens demonstrated a significant PFS advantage over SOC monotherapy in intention-to-treat populations [hazard ratio (HR) = 0.8, 95% confidence interval (CI): 0.65-0.98,
conclusionThe findings indicated that integrating PD-1/L1 blocking agents with SOC regimens for mCRC as first-line treatment failed to demonstrate significant improvements in ORR. Existing clinical data remain inadequate to establish OS advantages, particularly in patients with MSS/pMMR, despite exhibiting manageable toxicity profiles. Subsequent confirmation through rigorously designed phase III clinical trials remains essential to verify these therapeutic outcomes.
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