{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:42:36Z","timestamp":1792899756150,"version":"4.5.0"},"reference-count":34,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"\n PURPOSE<\/jats:title>\n Consensus molecular subtypes (CMSs) of metastatic colorectal cancer (mCRC) are debatable biomarkers. An individual patient data (IPD) meta-analysis was performed to test for impact on objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS), and treatment interaction.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n IPD (\n RAS<\/jats:italic>\n wild-type [WT] tumors treated per protocol [fluorouracil\/capecitabine, irinotecan\/oxaliplatin, anti\u2013vascular endothelial growth factor {VEGF}\/anti\u2013epidermal growth factor receptor {EGFR} antibodies] and with evaluable CMSs) were collected from five trials identified in PubMed, Embase, Medline, Cochrane Library, and proceedings of ASCO\/European Society for Medical Oncology: FIRE1 (no identifier), FIRE3 (ClinicalTrials.gov identifier:\n NCT00433927<\/jats:ext-link>\n ), XELAVIRI (ClinicalTrials.gov identifier:\n NCT01249638<\/jats:ext-link>\n ), PanaMa (ClinicalTrials.gov identifier:\n NCT01991873<\/jats:ext-link>\n ), and TRIBE2 (ClinicalTrials.gov identifier:\n NCT02339116<\/jats:ext-link>\n ). The one-step IPD meta-analysis approach assessed data taking the clustering of patients in the studies into account (ORR: generalized estimating equations models; PFS\/OS: Cox models).\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Seven hundred ninety patients were included: CMS1, n = 77 (9.7%); CMS2, n = 345 (43.7%); CMS3, n = 74 (9.4%); and CMS4, n = 294 (37.2%). Between-study heterogeneity was negligible (variance < 1 \u00d7 10\n \u22126<\/jats:sup>\n ). Compared with CMS1, CMS2 and CMS4 tumors had numerically higher odds ratios (OR) for ORR (CMS2: OR, 1.668 [95% CI, 0.982 to 2.836];\n P<\/jats:italic>\n = .059; CMS4: OR, 1.369 [95% CI, 0.874 to 2.146];\n P<\/jats:italic>\n = .170), and longer PFS (CMS2: hazard ratios [HR], 0.64 [95% CI, 0.48 to 0.85];\n P<\/jats:italic>\n = .002; CMS4: HR, 0.67 [95% CI, 0.50 to 0.91];\n P<\/jats:italic>\n = .009) and OS (CMS2: HR, 0.59 [95% CI, 0.43 to 0.80];\n P<\/jats:italic>\n < .001; CMS4: HR, 0.67 [95% CI, 0.49 to 0.92];\n P<\/jats:italic>\n = .01). The use of anti-EGFR versus anti-VEGF antibodies meaningfully improved PFS (HR, 0.67 [95% CI, 0.46 to 0.97];\n P<\/jats:italic>\n = .03) and OS (HR, 0.49 [95% CI, 0.33 to 0.72];\n P<\/jats:italic>\n < .001) in CMS4 tumors and was consistently observed for CMS4\n RAS<\/jats:italic>\n \/\n BRAF<\/jats:italic>\n WT (HR, 0.55 [95% CI, 0.37 to 0.83];\n P<\/jats:italic>\n = .004) or microsatellite stable status (HR, 0.52 [95% CI, 0.32 to 0.86];\n P<\/jats:italic>\n = .01). The interaction test of antibody treatment with CMSs was significant for PFS (\n P<\/jats:italic>\n < .001) and OS (\n P<\/jats:italic>\n < .001) in all patients and for OS in patients with\n RAS<\/jats:italic>\n \/\n BRAF<\/jats:italic>\n WT tumors (\n P<\/jats:italic>\n = .02).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n CMS4 might be an additional biomarker of anti-EGFR treatment efficacy in\n RAS<\/jats:italic>\n (and\n BRAF<\/jats:italic>\n ) WT mCRC.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/jco-25-00596","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T20:59:26Z","timestamp":1763499566000},"page":"31-41","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Individual Patient Data Meta-Analysis of Consensus Molecular Subtypes as Biomarkers of First-Line Treatment in\n RAS<\/i>\n Wild-Type Metastatic Colorectal Cancer"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct01249638","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00433927","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02339116","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01991873","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1041-0137","authenticated-orcid":true,"given":"Arndt","family":"Stahler","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology and Cancer Immunology, Charit\u00e9\u2014Universitaetsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Centre (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-0599","authenticated-orcid":true,"given":"Dominik Paul","family":"Modest","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cancer Immunology, Charit\u00e9\u2014Universitaetsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Centre (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3297-5801","authenticated-orcid":true,"given":"Sebastian","family":"Stintzing","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cancer Immunology, Charit\u00e9\u2014Universitaetsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Centre (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9739-408X","authenticated-orcid":true,"given":"Beatrice","family":"Borelli","sequence":"additional","affiliation":[{"name":"U.O. Oncologica Medica 2 Universitaria, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3603-534X","authenticated-orcid":true,"given":"Theresa","family":"Keller","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universitaetsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute for Biometry and Clinical Epidemiology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swantje","family":"Held","sequence":"additional","affiliation":[{"name":"ClinAssess GmbH, Leverkusen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Fischer von Weikersthal","sequence":"additional","affiliation":[{"name":"Klinikum St Marien, Oncology, Amberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9252-4650","authenticated-orcid":true,"given":"Lothar","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Oncology Practice UnterEms, Leer, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6082-7710","authenticated-orcid":true,"given":"Ullrich","family":"Graeven","sequence":"additional","affiliation":[{"name":"Kliniken Maria Hilf GmbH, M\u00f6nchengladbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Decker","sequence":"additional","affiliation":[{"name":"Onkologische Praxis, Ravensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Heintges","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Rheinland Klinikum Neuss, Lukaskrankenhaus, Neuss, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-5928","authenticated-orcid":false,"given":"Christoph","family":"Kahl","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Palliative Care, Klinikum Magdeburg gGmbH, Magdeburg, Germany"},{"name":"Department of Hematology, Oncology, and Palliative Care, University of Rostock, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beeke","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cancer Immunology, Charit\u00e9\u2014Universitaetsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kiani","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Klinikum Bayreuth GmbH, Bayreuth, Germany"},{"name":"Comprehensive Cancer Center Erlangen EMN, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Kaiser","sequence":"additional","affiliation":[{"name":"VK&K Studien GbR, Landshut, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8865-7282","authenticated-orcid":true,"given":"Ingo","family":"Schwaner","sequence":"additional","affiliation":[{"name":"Onkologische Schwerpunktpraxis Kurf\u00fcrstendamm, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Fruehauf","sequence":"additional","affiliation":[{"name":"Dr Hancken Hospital, Stade, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meinolf","family":"Karthaus","sequence":"additional","affiliation":[{"name":"MVZ Perlach, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Trarbach","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, West German Cancer Center, Westdeutsches Tumorzentrum, University Hospital of Essen, Essen, Germany"},{"name":"Reha-Zentrum am Meer, Niedersachsen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9131-2389","authenticated-orcid":true,"given":"Frederick","family":"Klauschen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4755-5743","authenticated-orcid":true,"given":"David","family":"Horst","sequence":"additional","affiliation":[{"name":"Department of Pathology, Charit\u00e9\u2014Universitaetsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0520-4841","authenticated-orcid":true,"given":"Chiara","family":"Cremolini","sequence":"additional","affiliation":[{"name":"U.O. 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