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Cancer Discov. 2017 Jun;7(6):586-595. doi: 10.1158/2159-8290.CD-16-1396. Epub 2017 Apr 1.

High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial.

Author information

1
Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
2
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.
3
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.
4
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.
5
Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Villejuif, France.
6
Département de Radiologie, Gustave Roussy, Villejuif, France.
7
Département de Cancérologie Cervico Faciale, Gustave Roussy, Villejuif, France.
8
Département de Biologie et Pathologie médicales, Gustave Roussy, Villejuif, France.
9
Plateforme de Bioinformatique, UMS AMMICA, Gustave Roussy, Villejuif, France.
10
Département de Radiologie interventionnelle, Gustave Roussy, Villejuif, France.
11
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.
12
Functional Genomics Unit, Gustave Roussy, Villejuif, France; Département de Biologie et Pathologie médicales, Gustave Roussy, Villejuif, France.
13
Functional Genomics Unit, Gustave Roussy, Villejuif, France; Laboratoire de Recherche Translationnelle et Centre de Ressources Biologiques, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, France.
14
Drug Development Department (DITEP), Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
15
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.
16
Direction de la Recherche Clinique, Gustave Roussy, Villejuif, France.
17
Gustave Roussy, Université Paris-Saclay, Villejuif, France.
18
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.
19
Drug Development Department (DITEP), Inserm Unit U981, Université Paris Saclay, Université Paris-Sud, Gustave Roussy, Villejuif, France.

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.

PMID:
28365644
DOI:
10.1158/2159-8290.CD-16-1396
[Indexed for MEDLINE]
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