Résumé
In the past two decades, substantial progresses have been made in the management of metastatic colorectal cancer (mCRC). However it remains important to aid selection of patients likely to respond to therapy thereby improving outcomes. Recently, through global gene expression profiles of primary tumors, independent groups have proposed new molecular classifications in mCRC. Different classifiers were determined leading to the identification of 3 to 6 molecular subtypes. The samples analyzed were mostly Stage II-III CRC and mainly prognostic correlations were assessed. However, implication for therapy of these new classifications is not yet really determined even if a link between subtypes and drug responses has been suggested.
Our study aimed to assess, in stage IV patients, if these subtypes are differentially responsive to mCRC therapies and are correlated with overall survival (OS) and Progression Free Survival (PFS). To this end, we collected and analyzed tumor samples from three cohorts representing 143 patients (REGP, a prospective monocenter study, COSIVAL a retrospective multicenter study and BIOCOLON a prospective multicenter study). Patients were treated with different regimens as first-line treatment: 79 patients received FOLFIRI regimen, 22 patients received FOLFIRI plus Bevacizumab, 32 patients received FOLFOX regimen. All the samples were analyzed using the gene expression platform previously used to identify CRC molecular subtypes. We demonstrated that: (1) the molecular subtypes identified in the three original publications are all present in our dataset and can be used to stratify mCRC patients, (2) Marisa's classification is correlated with response to FOLFIRI based-treatment, and (3) a particular molecular subtype is associated with a longer OS and PFS when patients were treated with FOLFIRI.
In conclusion we demonstrate that mCRC can be classified using the same molecular subtypes previously described in less advanced stages, and that the classification described by Marisa is predictive of the response to FOLFIRI and Cetuximab but not to FOLFOX or FOLFIRI/Bevacizumab regimens. These results show that patients' treatment could be improved by analyzing the molecular profile of their tumors, and open the way to individualized therapies with better efficacy in mCRC.
Citation Format: Maguy DEL RIO, Caroline Mollevi, Frederic Bibeau, Nadia VIE, Janick Selves, Jean François Emile, Pascal Roger, Celine Gongora, Jacques Robert, Nicole Tubiana, Marc Ychou, Pierre Martineau. Molecular subtypes of metastatic colorectal cancer are predictive of patient response to chemo and targeted therapies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B103.