WINTHER Trial: Genomic and Transcriptomic Profiling May Translate to New Therapeutic Options for Patients With Advanced Cancer
Published by Rodon et al in Nature Medicine, results of the WINTHER study showed 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 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 study 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.
Study Details
Patients were first evaluated for targetable alterations in cancer driver genes. Those who were not matched to treatments 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.
A total of 303 patients were enrolled in WINTHER, 107 of whom were ultimately treated according to recommendations made by a committee of cancer experts spanning 5 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.
Results
Overall, the WINTHER trial succeeded in matching personalized therapy to 35% of patients with advanced cancer. 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.
“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…. [O]ur findings represent an important step toward delivering on the true promise of precision medicine in oncology,” said Richard L. Schilsky, MD, FACP, FSCT, FASCO, Chairman of the WIN Consortium and Chief Medical Officer of ASCO.
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 vs 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, MD, co-leader of the WINTHER trial and Director of the University of California, San Diego, 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, MD, PhD, Vice-Chairman of the WIN Consortium, Director of the Vall d’Hebron Institute of Oncology, and President of the European Society for Medical Oncology.
Disclosure: WINTHER received funding from the European Union Seventh Framework Program, ARC Foundation for Cancer Research, Pfizer Oncology, Lilly France SAS, and Novartis Pharmaceuticals Corporation. For full disclosures of the study authors, visit nature.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
