Alain Viari, Casilda Rodríguez, J.-Y. Blay, Sandrine Boyault, Benoit You, Olivier Collard, ProfiLER investigators, Christian Baudet, Qing Wang, Gwenaelle Garin, I. Treillleux, J. Fayette, A. de la Fouchardière, D. Perol, Cécile Leyronnas, P. A. Cassier, Olivier Tredan, Pierre Guibert, Valéry Attignon, Matthieu Sarabi, V. Agrapart, Emilie Sohier, Thomas Bachelot, Sylvie Lantuejoul, Françoise Desseigne, I.L. Ray-Coquard, Maurice Pérol, Sandrine Paindavoine, Pierre-Etienne Heudel, Alice Bonneville-Levard, J.-P. Villemin, Aude Flechon, V. Corset, D. Frappaz, Daniel Pissaloux, C. de la Fouchardiere, N. Bonnin, Sylvie Chabaud, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation des régulations physiologiques (ORPHY (EA 4324)), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre Léon Bérard [Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hospices Civils de Lyon, Departement de Neurologie (HCL), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Groupe Hospitalier Mutualiste [Grenoble] (GHM), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL)
Background Antitumor activity of molecular-targeted agents is guided by the presence of documented genomic alteration in specific histological subtypes. We aim to explore the feasibility, efficacy and therapeutic impact of molecular profiling in routine setting. Patients and methods This multicentric prospective study enrolled adult or pediatric patients with solid or hematological advanced cancer previously treated in advanced/metastatic setting and noneligible to curative treatment. Each molecular profile was established on tumor, relapse or biopsies, and reviewed by a molecular tumor board (MTB) to identify molecular-based recommended therapies (MBRT). The main outcome was to assess the incidence rate of genomic mutations in routine setting, across specific histological types. Secondary objectives included a description of patients with actionable alterations and for whom MBRT was initiated, and overall response rate. Results Four centers included 2579 patients from February 2013 to February 2017, and the MTB reviewed the molecular profiles achieved for 1980 (76.8%) patients. The most frequently altered genes were CDKN2A (N=181, 7%), KRAS (N=177, 7%), PIK3CA (N=185, 7%), and CCND1 (N=104, 4%). An MBRT was recommended for 699/2579 patients (27%), and only 163/2579 patients (6%) received at least one MBRT. Out of the 182 lines of MBRT initiated, 23 (13%) partial responses were observed. However, only 0.9% of the whole cohort experienced an objective response. Conclusion An MBRT was provided for 27% of patients in our study, but only 6% of patients actually received matched therapy with an overall response rate of 0.9%. Molecular screening should not be used at present to guide decision-making in routine clinical practice outside of clinical trials. This trial is registered with ClinicalTrials.gov, number NCT01774409.