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

Published on Jun 1, 2017in Cancer Discovery26.37
· DOI :10.1158/2159-8290.CD-16-1396
Christophe Massard43
Estimated H-index: 43
(Université Paris-Saclay),
Stefan Michiels50
Estimated H-index: 50
(Université Paris-Saclay)
+ 30 AuthorsJean-Charles Soria79
Estimated H-index: 79
(Université Paris-Saclay)
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. 552 . This article is highlighted in the In This Issue feature, p. 539
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