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The question that had emerged at the 2017 conference was whether to sequence or not the tumour of any patient's cancer. A recent study shows that RNA profiling, in addition to DNA profiling, allows more patients with advanced cancer to benefit from personalized therapies than standard DNA mutation tests done alone.

This is a first in clinical research. One study performed a transcriptomic analysis (RNA expression tests) to personalize treatment for a large number of patients, based on the level of RNA expression in tumors compared to normal tissues.

303 patients, who had already received several treatments, took part in the WINTHER trial, the first WIN Consortium study, published on April 22 in Nature Medicine (1). Of these, 25% had already received five or more line therapies. 107 were treated in accordance with the recommendations of a committee of cancer specialists coming from five different countries: 69 received a treatment chosen on the basis of DNA profiling and 38 received RNA profiling.

 

Personalized therapy for 35% of patients

In the WINTHER trial, personalized therapy was found for 35% of patients with advanced cancer. "The strategy used by the WINTHER trial resulted in a higher proportion of patients treated than in many other precision medicine trials. Previous studies had identified potential treatments for 5% to 25% of patients based exclusively on DNA profiling. The conclusions of the WINTHER trial therefore represent a significant step forward in the implementation of precision medicine in oncology," said Richard L. Schilsky, President of the WIN Consortium.

 

A patented algorithm used for analysis

During this study, an assessment of the target alterations in the tumor's DNA was initially performed. "Patients who could not benefit from targeted treatment based on DNA alterations were referred to personalized treatment based on gene expression differences between the tumor and healthy tissue," the researchers explained. The use of a patented algorithm developed by the WIN Consortium allowed the analysis of these differences. The researchers demonstrated that RNA expression could be used to increase patients' therapeutic options, with biopsy of normal tissues being safe and well accepted by patients.

 

Towards an increase in median overall survival

Patients who received personalized and optimized therapy based on alterations in their own DNA, or based on RNA profiling, responded better to treatment. For patients with a favourable performance index and optimal matching to therapy, median overall survival increased significantly (25.8 months, compared to 4.5 months for others). A correlation was also found between the degree of matching and progression-free survival, regardless of the number of previous therapies. "What our results demonstrate first and foremost is that patients treated with a drug or protocol that better matches the molecular profile of their tumour have a better response to treatment.

 

Sources

(1) Rodon J. et al. Genomic and transcriptomic profiling expands precision cancer medicine : the WINTHER trial. Nature Medicine, 22 avril 2019. Doi.org/10.1038/s41591-019-0424-4.