Individual patient data meta-analysis of consensus molecular subtypes as biomarkers in first-line treatment of RAS wild-type metastatic colorectal cancer

Consensus molecular subtypes (CMSs) of metastatic colorectal cancer (mCRC) are debatable biomarkers. German reseachers carried out an individual patient data (IPD) meta-analysis to test impact of CMSs on outcomes of mCRC. The analysis included 790 patients with RAS wild-type treated per protocol (fluorouracil/capeticabine, irinotecan/oxaliplatin, anti-VEGF/anti-EGFR antibodies in five trials (FIRE1, FIRE3, XELAVIRI, PaNaMa, and TRIBE2) with CMS1 (9.7%), CMS2 (43.7%), CMS3 (9.4%) and CMS4 (37.2%). Between-study heterogeneity was negligible. Compared wiith CMS1, CMS2 and CMS4 tumors had numerically higher odds ratios for objective response rate (CMS2: OR 1.669; p=0.059 and CMS4: OR 1.369; p=0.170) and longer progression-free survival (CMS 2: HR 0.64; p=0.002 and CMS4: HR 0.67; p=0.09) and longer overall survival (CMS2: HR 0.59; p<0.001 and CMS4: HR 0.67; p=0.01). In CMS4 tumors, the use of anti-EGFR versus anti-VEGF antibodies improved PFS (HR 0.67; p=0.03) and OS (HR 0.49; pxtagstartz0.001), which was consistently observed for CMS4