title: High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial.
abstract: High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the clinical benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing. The primary objective was to evaluate clinical benefit as measured by the percentage of patients presenting progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than the PFS on prior therapy (PFS1). A total of 1,035 adult patients were included, and a biopsy was performed in 948. An actionable molecular alteration was identified in 411 of 843 patients with a molecular portrait. A total of 199 patients were treated with a targeted therapy matched to a genomic alteration. The PFS2/PFS1 ratio was >1.3 in 33% of the patients (63/193). Objective responses were observed in 22 of 194 patients (11%; 95% CI, 7%-17%), and median overall survival was 11.9 months (95% CI, 9.5-14.3 months).Significance:This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach. Randomized trials are needed to validate this hypothesis and to quantify the magnitude of benefit. Expanding drug access could increase the percentage of patients who benefit.Cancer Discov; 7(6); 586-95. ©2017 AACR.See related commentary by Schram and Hyman, p. 552This article is highlighted in the In This Issue feature, p. 539.
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Service de biostatistique et d'épidémiologie, Villejuif, France; CESP, INSERM, Fac. de médecine-Univ. Paris-Sud, Université Paris-Saclay Villejuif, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Ferté
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Service de biostatistique et d'épidémiologie, Villejuif, France; CESP, INSERM, Fac. de médecine-Univ. Paris-Sud, Université Paris-Saclay Villejuif, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.affiliation: Laboratoire de Recherche Translationnelle et Centre de Ressources Biologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, France; Département de Biologie et Pathologie médicales, Gustave Roussy, Villejuif, France; INSERM Unit U981, Gustave Roussy, Villejuif, France; Faculté de Médecine, Kremlin-Bicêtre, Université Paris Sud, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Hollebecque
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Verlingue
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Villejuif, France; Laboratoire de Recherche Translationnelle et Centre de Ressources Biologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, France.
authors.forename: Ecaterina
authors.initials: E
authors.lastname: Ileana
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Villejuif, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rosellini
authors.affiliation: Département de Radiologie, Gustave Roussy, Villejuif, France.
authors.forename: Samy
authors.initials: S
authors.lastname: Ammari
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Ngo-Camus
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Rastislav
authors.initials: R
authors.lastname: Bahleda
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Anas
authors.initials: A
authors.lastname: Gazzah
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varga
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Département de Cancérologie Cervico Faciale, Gustave Roussy, Villejuif, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Even
authors.affiliation: Département de Cancérologie Cervico Faciale, Gustave Roussy, Villejuif, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Breuskin
authors.affiliation: Département de Biologie et Pathologie médicales, Gustave Roussy, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Auger
authors.affiliation: Plateforme de Bioinformatique, UMS AMMICA, Gustave Roussy, Villejuif, France.
authors.forename: Bastien
authors.initials: B
authors.lastname: Job
authors.affiliation: Département de Radiologie interventionnelle, Gustave Roussy, Villejuif, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: De Baere
authors.affiliation: Département de Radiologie interventionnelle, Gustave Roussy, Villejuif, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Deschamps
authors.affiliation: Département de Biologie et Pathologie médicales, Gustave Roussy, Villejuif, France; Laboratoire de Recherche Translationnelle et Centre de Ressources Biologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vielh
authors.affiliation: Département de Biologie et Pathologie médicales, Gustave Roussy, Villejuif, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.affiliation: Functional Genomics Unit, Gustave Roussy, Villejuif, France; Département de Biologie et Pathologie médicales, Gustave Roussy, Villejuif, France.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.affiliation: Functional Genomics Unit, Gustave Roussy, Villejuif, France; Laboratoire de Recherche Translationnelle et Centre de Ressources Biologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Richon
authors.affiliation: Drug Development Department (DITEP), Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.affiliation: Department of Radiation Oncology, Drug Development Department (DITEP), INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, Villejuif, France; University Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Angevin
authors.affiliation: Direction de la Recherche Clinique, Gustave Roussy, Villejuif, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.affiliation: INSERM Unit U981, Gustave Roussy, Villejuif, France; Faculté de Médecine, Kremlin-Bicêtre, Université Paris Sud, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France. fandre@igr.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.affiliation: Drug Development Department (DITEP), Inserm Unit U981, Université Paris Saclay, Université Paris-Sud, Gustave Roussy, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult