ArticleESMO open2025
Efficacy of pembrolizumab in microsatellite-stable, tumor mutational burden-high metastatic colorectal cancer: genomic signatures and clinical outcomes.
Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Screening of known gut microbiome-derived metabolites in anti-tumor immunity of colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- Review
- SLC7A5 promotes colorectal cancer liver metastasis by reprogramming tryptophan metabolism through the Kyn/XANA‒AhR axis and reshaping the immune microenvironment.Clinical and translational medicine · 2026Article
- Prolonged response to pembrolizumab in BRAFV600E microsatellite stable metastatic colorectal cancer following an increase in tumor mutational burden.The oncologist · 2026Article
- Leveraging glucan-induced trained immunity for the epigenetic and metabolic rewiring of macrophages to enhance colorectal cancer vaccine response.Nature communications · 2026Article
- Integrative multi-omics and machine learning framework identifies PRDX4 as a redox-EMT regulator and predictive marker in bone-metastatic breast cancer.NPJ precision oncology · 2026Article
- The tumor immune microenvironment of thyroid cancer and colorectal cancer: cellular crosstalk and therapeutic implications.Frontiers in immunology · 2026Review
- Mechanisms of immune resistance in microsatellite-stable colorectal cancer.Frontiers in oncology · 2026Review
- Nationwide Real-World Usage of Blood-Based (Liquid) Biomarker Testing in Japan.Cancer science · 2025Article
- Clinical utility of comprehensive genomic profiling test for colorectal cancer: a single institution prospective observational study.Journal of cancer research and clinical oncology · 2025Observational
- Association of KRAS variants with survival and therapeutic outcomes in biliary tract cancers.ESMO open · 2025Article
- CD8+ T Cell Subsets as Biomarkers for Predicting Checkpoint Therapy Outcomes in Cancer Immunotherapy.Biomedicines · 2025Review
- Pembrolizumab versus bevacizumab plus modified FOLFOX6 in metastatic MSI-H/dMMR colorectal cancer: a multicenter retrospective study with CT evaluation.Frontiers in oncology · 2025Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPembrolizumab, an immune checkpoint inhibitor (ICI), shows significant survival benefits in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but its efficacy in microsatellite-stable (MSS) mCRC is limited. Although ICIs are effective in tumor mutational burden-high (TMB-H) solid tumors, the impact on MSS-TMB-H mCRC, a rare subset within MSS mCRC, remains unclear. MATERIALS AND
methodsWe conducted a retrospective analysis using clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) repository in Japan. Patients with MSS-TMB-H mCRC who underwent tissue-based comprehensive genomic profiling and were treated with pembrolizumab or other later-line therapies were included. Pembrolizumab's efficacy was compared with that of trifluridine/tipiracil (FTD/TPI) and regorafenib. Genomic profiles of MSS-TMB-H, MSI-H-TMB-H, and MSS-TMB-low (TMB-L) CRCs were analyzed across 71 cancer-related genes.
resultsAmong 127 TMB-H mCRC cases treated with pembrolizumab in the C-CAT repository, 77 were MSS and 50 were MSI-H. Pembrolizumab showed significantly shorter time to treatment failure (TTF) and overall survival (OS) in patients with MSS-TMB-H mCRC compared with those with MSI-H-TMB-H mCRC [median TTF 2.0 versus 10.6 months; hazard ratio (HR) 4.79, 95% confidence interval (CI) 2.65-8.64, median OS 4.5 versus 33.6 months; HR 9.86, 95% CI 3.93-24.77, both P < 0.0001]. Among MSS-TMB-H mCRC patients, 19 received pembrolizumab, 73 received FTD/TPI (±bevacizumab), and 18 received regorafenib as their first later-line therapy. Pembrolizumab showed significantly shorter TTF and OS compared with FTD/TPI (median TTF 1.6 versus 4.1 months; HR 2.66, 95% CI 1.41-5.02, P = 0.0017, median OS 5.4 versus 13.8 months; HR 2.42, 95% CI, 1.09-5.38, P = 0.025). Genomic analysis of 6737 CRCs revealed that MSS-TMB-H CRCs harbored fewer pathogenic alterations than MSI-H-TMB-H CRCs but had a profile similar to MSS-TMB-L CRCs.
conclusionsPembrolizumab may be less effective than FTD/TPI in later-line treatment of MSS-TMB-H mCRC, potentially due to genomic similarities between MSS-TMB-H and MSS-TMB-L CRC, suggesting the need for alternative therapeutic strategies in this subgroup.
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