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

Posted: Monday, April 22, 2019


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

WIN represents a global collaboration of cancer centers, life science and biotech organizations, pharmaceutical and technology companies and not-for-profit organizations.
The Worldwide Innovative Networking (WIN) Consortium in personalized cancer medicine was initiated in 2010 with leadership from leading cancer centers worldwide. WIN is a non-profit, non-governmental organization headquartered in Paris.

WIN was created to accelerate the pace and reduce the cost of translating novel cancer treatments to the bedside by developing and applying, through worldwide clinical trials and research projects, the most promising advances in genomic-based cancer research. WIN aims to initiate research projects each year in a global consortium guided by an independent scientific advisory board.

WIN now includes 36 institutional members. These stakeholders have come together from all parts of the world to address the challenge of increasing the efficacy of cancer diagnostics and therapeutics by understanding the genetics and biology of each individual’s tumor and accounting for genetic differences across diverse populations—from North and South America, Europe, Asia, and the Middle East.

Our goal is to significantly improve outcomes for patients around the globe. We aim to increase the number of patients worldwide that have access to innovative, global clinical trials in the area of genomic-based cancer therapeutics. Global diversity and inclusion of all stakeholders is WIN’s most important and differentiating asset.
WIN is comprised of organizations representing all stakeholders in personalized cancer medicine.
WIN enables cross-sector collaborations designed to accelerate the speed and efficacy with which breakthroughs in personalized cancer medicine can be realized and brought to patients worldwide.

Our members include leading academic, pharmaceutical, life science, not-for-profit, health, patient advocacy and IT organizations.
Our members include 27 leading academic centers representing 20 countries and four continents, enabling coordinated studies with a global patient population.
The response to a genetically-targeted therapy can vary due to differences in ethnicity and environment. WIN's global studies are designed to identify and account for this variability, enhancing the speed and efficacy with which novel discoveries can be made and brought to patients around the world.

WIN prioritizes cross-sector interaction designed to enhance learning across and between continents and healthcare sectors.
WIN Symposia, held annually, brings together hundreds of leaders representing all stakeholders from around the world in a forum designed to promote the exchange of ideas and information.