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Comprehensive Tumor Profiling Promises New Therapeutic Options for Patients with Advanced Cancer

VILLEJUIF, France–(BUSINESS WIRE)–Published in Nature Medicine* today, results of
WINTHER, the first study pioneered by the WIN Consortium** – – Genomic
and transcriptomic profiling expands precision cancer medicine: the
WINTHER trial –
shows that RNA profiling together
with DNA testing matches more patients with advanced cancer to
personalized therapies than DNA profiling for tumor mutations alone.

The WINTHER trial***, NCT01856296, led by investigators from Vall
d’Hebron Institute of Oncology – VHIO (Spain), Chaim Sheba Medical
Center (Israel) (Raanan Berger), Gustave Roussy (France) (Jean-Charles
Soria), Centre Léon Bérard (France) (Pierre Saintigny), Segal Cancer
Centre, McGill University (Canada) (Wilson H. Miller), UT MD Anderson
Cancer Center (USA) (Jordi Rodon and Apostolia-Maria Tsimberidou) and
University of California San Diego, Moores Cancer Center (USA) (Razelle
Kurzrock), aimed to expand precision oncology to patients with advanced
solid tumors that progressed after treatment with standard therapies.

For the first time in the clinic, the WINTHER trial applied
transcriptomics (RNA expression testing) to tailor precision medicine in
oncology to a greater number of patients based on the increased
expression of RNA in tumors compared to normal tissues.

303 patients were enrolled in WINTHER; 107 of whom were ultimately
treated according to recommendations made by a committee of cancer
experts spanning five countries. These patients had been heavily
pretreated, with one quarter having received five or more prior lines of
therapy. Of the 107 patients treated, 69 received treatment based on DNA
mutation profiling, and 38 based on RNA profiling. Overall, the WINTHER
trial succeeded in matching personalized therapy to 35% of patients with
advanced cancer.

“The strategy employed in WINTHER resulted in a higher proportion of
patients treated than in many precision medicine trials. Previous
studies have identified potential treatments for between 5% and 25 % of
patients based on DNA profiling alone, our findings represent an
important step toward delivering on the true promise of precision
medicine in oncology,”
said Richard L. Schilsky, Chairman WIN
Consortium and Chief Medical Officer of ASCO.

In this trial, patients were first evaluated for targetable alterations
in cancer driver genes. Those who were not matched to drugs based on DNA
alterations received a treatment tailored to the differences in gene
expression between patients’ tumors and normal tissues which were
assessed using a patented algorithm developed by the WIN Consortium.
Comparisons with normal tissues proved essential due to highly variable
RNA expression between patients and across normal tissue types. The
WINTHER researchers showed that RNA expression can be used to expand
personalized therapy options for patients and that normal tissue biopsy
is safe and accepted by patients.

Patients who received therapy optimally tailored to their respective DNA
alterations, or consistent with the algorithm recommendation for RNA
guided treatment, responded better. Patients with a good performance
status and a high degree of matching had a significantly longer median
overall survival of 25.8 months versus 4.5 months for others. There was
also a correlation between degree of matching and progression-free
survival independent of the number of prior therapies. “Importantly,
our results show that patients treated with a drug or regimen more
closely matched to the molecular profile of their tumor, do better,”
observed
Razelle Kurzrock, co-leader of the WINTHER trial and Director of UCSD
Moores Center for Personalized Cancer Therapy.

Assessing RNA is an important adjunct to DNA profiling for
determining precision treatments. WINTHER rings in a new era for
personalized medicine in oncology
,” concluded Josep Tabernero,
Vice-Chairman WIN Consortium, Director VHIO and President ESMO.

* https://doi.org/10.1038/s41591-019-0424-4
**
About WIN: WIN
Consortium
 is a non-profit organization based in Paris, France. We
are a worldwide network assembling cancer stakeholders from four
continents to develop cutting edge concepts and clinical trials that
improve survival for cancer patients. WIN members include 28 outstanding
cancer centers plus 8 additional leading pharmaceutical, technology
companies and patient advocacy organizations representing stakeholders
in precision cancer medicine, www.winconsortium.org
***
WINTHER received funding from the European Union Seventh Framework
Program (FP7/2007-2013 under grant agreement n°306125), ARC Foundation
for cancer research (France), Pfizer Oncology, Lilly France SAS, and
Novartis Pharmaceuticals Corporation.

Contacts

Vladimir Lazar
vladimir.lazar@winconsortium.org
33661091522

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