Lenz HJ, et al. - In patients enrolled in CALGB/SWOG 80405, researchers investigated the consensus molecular subtypes (CMSs) of colorectal cancer (CRC) that represent a merging of gene expression–based features largely in primary tumors from six independent classification systems for predictive and prognostic value. Furthermore, they sought to provide a framework for capturing the intrinsic heterogeneity of CRC. Comparison of the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin, and oxaliplatin or fluorouracil, leucovorin, and irinotecan as first-line treatment of advanced CRC was done in CALGB/SWOG 80405, a phase III trial. As per findings, overall survival and progression-free survival prognosis and prediction could be made by assessing CMSs. A significantly longer overall survival (OS) was observed for patients treated with bevacizumab than those treated with cetuximab in the CMS1 cohort. They observed significantly longer OS for patients treated with cetuximab than patients treated with bevacizumab in the CMS2 cohort. These findings support the refinement of the CMS classification for recognizing patients with metastatic CRC who may particularly benefit from specific targeted therapy as part of the initial treatment.