Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial

Jordi Rodon, Jean Charles Soria, Raanan Berger, Wilson H. Miller, Eitan Rubin, Aleksandra Kugel, Apostolia Tsimberidou, Pierre Saintigny, Aliza Ackerstein, Irene Braña, Yohann Loriot, Mohammad Afshar, Vincent Miller, Fanny Wunder, Catherine Bresson, Jean François Martini, Jacques Raynaud, John Mendelsohn, Gerald Batist, Amir OnnJosep Tabernero, Richard L. Schilsky, Vladimir Lazar, J. Jack Lee, Razelle Kurzrock

Research output: Contribution to journalArticlepeer-review

318 Scopus citations

Abstract

Precision medicine focuses on DNA abnormalities, but not all tumors have tractable genomic alterations. The WINTHER trial (NCT01856296) navigated patients to therapy on the basis of fresh biopsy-derived DNA sequencing (arm A; 236 gene panel) or RNA expression (arm B; comparing tumor to normal). The clinical management committee (investigators from five countries) recommended therapies, prioritizing genomic matches; physicians determined the therapy given. Matching scores were calculated post-hoc for each patient, according to drugs received: for DNA, the number of alterations matched divided by the total alteration number; for RNA, expression-matched drug ranks. Overall, 303 patients consented; 107 (35%; 69 in arm A and 38 in arm B) were evaluable for therapy. The median number of previous therapies was three. The most common diagnoses were colon, head and neck, and lung cancers. Among the 107 patients, the rate of stable disease ≥6 months and partial or complete response was 26.2% (arm A: 23.2%; arm B: 31.6% (P = 0.37)). The patient proportion with WINTHER versus previous therapy progression-free survival ratio of >1.5 was 22.4%, which did not meet the pre-specified primary end point. Fewer previous therapies, better performance status and higher matching score correlated with longer progression-free survival (all P < 0.05, multivariate). Our study shows that genomic and transcriptomic profiling are both useful for improving therapy recommendations and patient outcome, and expands personalized cancer treatment.

Original languageEnglish
Pages (from-to)751-758
Number of pages8
JournalNature Medicine
Volume25
Issue number5
DOIs
StatePublished - 1 May 2019

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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