SynthesisPloS one2025
The efficacy of Pembrolizumab, Ipilimumab, and Nivolumab monotherapy and combination for colorectal cancer: A systematic review and meta-analysis.
Synthesis in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Review
- Nanomedicine delivery systems remodel the immunosuppressive microenvironment of colorectal cancer: synergistic strategies and mechanisms of targeted immune checkpoint inhibitors.Frontiers in immunology · 2026Review
- Multi-omics and AI-driven immune subtyping to optimize neoantigen-based vaccines for colorectal cancer.Scientific reports · 2025Article
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Authors and funding
12 authors.
Funding
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Abstract
backgroundColorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, with cases expected to rise 60% by 2030, especially in Asia. Metastatic CRC (mCRC) has a poor 5-year survival rate of 14%, posing a major treatment challenge. Tumors with DNA mismatch repair deficiency (dMMR) and a high level of microsatellite instability (MSI-H) respond well to immune checkpoint inhibitors (ICIs), shifting treatment strategies. This systematic review and meta-analysis evaluate Pembrolizumab (PEM), Nivolumab (NIV), and Nivolumab plus Ipilimumab (NIV + IPI) for their promising antitumor efficacy in MSI-H/dMMR mCRC.
methodsThis systematic review followed PRISMA guidelines and Cochrane Handbook standards, covering studies from 2014 to 2024 on advanced CRC patients treated with ICIs. A comprehensive search across eight databases was conducted by 12 independent reviewers. Extracted outcomes included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and objective response rate (ORR). To facilitate pooled analysis, data reported as median and interquartile range (IQR), or median, minimum, and maximum were converted to mean and standard deviation (SD) using combined formulas by Luo D et al. and Wan X et al. Risk of bias was assessed using the Cochrane RoB 2 tool. Meta-analyses were performed using random-effects models, with subgroup analyses by dosage. Publication bias and sensitivity analyses were conducted. All statistical analyses used RevMan version 5.4.
resultsA total of 13 eligible studies were analyzed, with sample sizes ranging from 11 to 307 and follow-up durations between 5.3 and 44.5 months. NIV + IPI showed the highest efficacy across all endpoints: ORR 0.54 [95% CI: 0.45-0.65, I² = 75%], OS 0.84 [95% CI: 0.81-0.88, I² = 0%], PFS 0.73 [95% CI: 0.68-0.78, I² = 0%], and DCR 0.82 [95% CI: 0.77-0.86, I² = 0%]. This combination outperformed NIV alone, which demonstrated ORR 0.36 [95% CI: 0.21-0.60, I² = 81%], OS 0.73 [95% CI: 0.62-0.86, I² = 54%], PFS 0.54 [95% CI: 0.43-0.68, I² = 34%], and DCR 0.70 [95% CI: 0.64-0.77, I² = 0%]. PEM showed lower efficacy with ORR 0.33 [95% CI: 0.23-0.49, I² = 94.6%], OS 0.59 [95% CI: 0.31-0.66, I² = 94%], PFS 0.45 [95% CI: 0.31-0.66, I² = 84%], and DCR 0.73 [95% CI: 0.47-1.12, I² = 94%]. PEM's 200 mg dosage subgroup exhibited the best performance in its group with an ORR of 0.45 [95% CI: 0.38-0.52, I² = 0%]. Despite these findings, heterogeneity was notably high in PEM-related studies, highlighting variability in populations and study designs. Overall, NIV + IPI demonstrated superior and more consistent clinical outcomes.
conclusionsThis study highlights NIV + IPI as a promising combination for advanced CRC, showing superior efficacy, while PEM also demonstrated potential. However, high heterogeneity suggests the need for further research. Acknowledging its limitations, this study marks a pioneering effort in comparing short- and long-term effects of anti-CTLA-4 and anti-PD-1 therapies, paving the way for future advancements in CRC treatment.
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