In an individual patient meta-analysis reported in the Journal of Clinical Oncology, Stahler et al identified outcomes associated with consensus molecular subtypes (CMSs) in patients undergoing first-line treatment for RAS wild-type metastatic colorectal cancer.
Study Details
Individual patient data on 790 patients with RAS wild-type tumors and data on CMSs were obtained from five trials assessing fluorouracil/capecitabine or irinotecan/oxaliplatin with or without anti–vascular endothelial growth factor (VEGF)/anti–epidermal growth factor receptor (EGFR) antibodies. Objective response rate, progression-free survival, and overall survival were analyzed according to CMSs.
Key Findings
Among the 790 patients, 77 (9.7%) had CMS1, 345 (43.7%) had CMS2, 74 (9.4%) had CMS3, and 294 (37.2%) had CMS4 tumors.
Compared with patients with CMS1 tumors, those with CMS2 and CMS4 tumors had:
- Numerically increased likelihood of objective response (odds ratio [OR] = 1.67, P = .059; OR = 1.37, P = .170)
- Significantly prolonged progression-free survival (hazard ratio [HR] = 0.64, P = .002; HR = 0.67, P = .009)
- Significantly prolonged overall survival (HR = 0.59, P < .001; HR = 0.67, P = .01).
Treatment with anti-EGFR vs anti-VEGF antibodies significantly improved progression-free survival (HR = 0.67, P = .03) and overall survival (HR = 0.49, P < .001) among patients with CMS4 tumors; benefit was observed for patients with CMS4 tumors with wild-type RAS/BRAF (HR = 0.55, P = .004) and microsatellite-stable status (HR = 0.52, P = .01).
The test for interaction of antibody treatment with CMS was significant for progression-free survival (P < .001) and overall survival (P < .001) among all patients and for overall survival among patients with RAS/BRAF wild-type tumors (P = .02).
The investigators concluded: “CMS4 might be an additional biomarker of anti-EGFR treatment efficacy in RAS (and BRAF) [wild-type metastatic colorectal cancer].”
Arndt Stahler, MD, of the Department of Hematology, Oncology and Cancer Immunology, Charité—Universitaetsmedizin Berlin, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the German Translational Cancer Consortium (DKTK), Weigand-Bohnewand-Gravenhorst-Fonds, Sanofi-Aventis, Pfizer, Merck KGaA, Roche, and Amgen. For full disclosures of all study authors, visit ascopubs.org.
