Results from WINTHER: the relevance of RNA profiling in matching more patients to personalized anti-cancer therapies

Co-led by VHIO’s Director, Josep Tabernero, Jordi Rodón, Clinical Investigator at the MD Anderson Cancer Center (Texas, USA), and Associate Investigator of VHIO’s Research Unit for Molecular Therapy of Cancer (UTIM) – “la Caixa” (directed by Elena Garralda), and Irene Braña, Phase I Investigator at the same Unit – all co-first authors of this present paper – this clinical study sought to match a greater number of patients with advanced refractory solid tumors to personalized anti-cancer therapies based on either next generation or transcriptomic analysis.

Carried out in collaboration with other leading members of the WIN Consortium, WINTHER trial applied this novel approach in the clinic and succeeded in tailoring personalized medicines to more patients based on the increased expression of RNA in tumors compared to normal tissues.

Commenting for VHIO Communications, Josep Tabernero, co-first author and Vice-Chairman of WIN said, “The hope versus the realities of the molecular profiling of tumors for precision oncology has been widely and hotly debated in both lay and specialized media. Our results promise a bridging of this gap by successfully evidencing significant benefits in these patients through the addition of comprehensive RNA expression testing in the clinic”.

To discover more about this study and the encouraging results driven in partnership, please see below for today’s official news release issued by the WIN Consortium.

*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 Onn, Josep Tabernero, Richard L. Schilsky, Vladimir Lazar, J. Jack Lee, Razelle Kurzrock. Nat. Med. 2019. DOI: 10.1038/s41591-019-0424-4.

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Source: WIN Consortium

Comprehensive tumor profiling promises new therapeutic options for patients with advanced cancer

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 the 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 of the WIN Consortium and Chief Medical Officer of the American Society of Clinical Oncology (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, WIN Consortium Vice-Chairman, Director of VHIO and President of the European Society for Medical Oncology (ESMO).

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* 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 Onn, Josep Tabernero, Richard L. Schilsky, Vladimir Lazar, J. Jack Lee, Razelle Kurzrock. Nat. Med. 2019. DOI: 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.