Barcelona, September 2, 2020.- Led by Fernanda Mosele, Goustave Roussy (Villejuif, France), an international group of leading experts, including VHIO’s Joaquin Mateo, Principal Investigator of our Prostate Cancer Translational Research Group, and Rodrigo Dienstmann who directs VHIO’s Oncology Data Science Group (ODysSey), have recently published an open access recommendations paper in Annals of Oncology* on the use of Next-Generation Sequencing (NGS) in clinical practice for patients with metastatic disease.

NGS is a technology that rapidly sequences DNA from hundreds, or even thousands, of genes simultaneously, and at a relatively low cost.  It can provide more precise data on the genomic alterations present in each individual’s cancer with the objective of guiding treatment decisions matched to the molecular make up and particularities of each patient’s disease.

While only requiring small amounts of tissue, thus avoiding serial biopsies, there are certain limitations. Commenting for VHIO’s International Communications Joaquin Mateo noted, ” Cancer is an incredibly smart disease that evolves over time. It can therefore adapt to, and dodge, the anti-cancer effects of novel therapies. It is therefore critical to rapidly identify and combat these alterations throughout the course of disease.

He continued, “The European Society of Medical Oncology is the first scientific society to have developed recommendations on how to apply this widely implemented technique in the clinic. Led by ESMO’s Translational Research and Precision Medicine Working Group** , for which I currently serve as Chair, the paper outlines recommendations on which tumors from which patients should be tested using multi-gene NGS panels at three different levels. Namely, recommendations for daily practice with an impact on public health; recommendations for research to improve access to innovation; and patient-centric recommendations.”

Rodrigo Dienstmann, also co-author of the paper and contributor for the recommendations on colorectal cancer added, “In Europe NGS is mainly used in academic centers and translating the benefits of this technology to the clinic is currently complex. We hope that these early recommendations will help to unify decision-making on how to use NGS in routine clinical practice for patients suffering from metastatic disease including advanced lung adenocarcinoma, prostate cancer, ovarian cancer, and cholangiocarcinoma.”

The recommendations were elaborated based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) ranking for the genomic alterations that occur in the eight cancers responsible for the majority of deaths worldwide – lung, breast, colorectal, prostate, stomach, pancreatic, liver, and bile duct cancers. For each tumor type, using the ESCAT classification and the prevalence of abnormalities, the investigators estimated the number of patients who would need to be assessed with NGS to identify one who could be effectively treated in daily practice with a matched therapy.

Recommendations for daily practice with impact on public health include multigene panel testing for all patients with metastatic non-small cell lung (NSCLC), prostate, ovarian or bile duct cancer, as well as more specific recommendations proposed for other types of cancer.

Concerning research in academic centres and how to improve access to data and innovation, ESMO recommends access to NGS tests for patients participating in research studies or clinical trials, as is the case at VHIO with its leading screening program. The aim of this recommendation is for all clinical research centers to perform NGS in order to accelerate drug development. “To improve our understanding of how to treat patients based on precision biomarkers, we need to accumulate data from thousands of patients,” says Joaquin, who also contributed to the recommendations made for prostate cancer.

ESMO is taking the lead by calling on university hospitals and research centers to generate data and make it accessible in order to promote innovation, as we do at VHIO. This will enable us to more effectively use this technology for other tumor types.

Finally, patient-centered recommendations are highlighted where patients with other cancers could decide, along with their doctor, to request multi-gene NGS tests, providing there is no additional cost to the public health system and the patient is informed about the small probability of benefit (patient-centered perspective).

This recommendation acknowledges that a small number of patients may benefit from a given drug as they have a rare mutation,” explains Joaquin. “When an abnormality is rare, it is difficult to enrol enough patients for clinical trials that can generate the necessary evidence of the potential benefits of using NGS testing. Beyond the tumors for which all patients should have an NGS test, there is therefore room  for doctors and patients to weigh up the pros and cons of requesting these tests.”

He concluded, “Our paper represents a forward step in more effectively applying precision medicine to daily clinical practice, and also highlights the problem of rare cancer subtypes or the most common biomarkers in specific populations that may be under represented in clinical studies. ESMO is thus committed to providing evidence-based guidance on the use of NGS to promote equitable access to optimal care for all cancer patients.”

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References

*Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, Normanno N, Scarpa A, Robson M, Meric-Bernstam F, Wagle N, Stenzinger A, Bonastre J, Bayle A, Michiels S, Bièche I, Rouleau E, Jezdic S, Douillard JY, Reis-Filho J, Dienstmann R, André F, Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: A report from the ESMO Precision Medicine Working Group, Annals of Oncology (2020), doi: https://doi.org/10.1016/j.annonc.2020.07.014.

**ESMO’s Translational Research Working Group promotes high-quality translational research in oncology and to develop translational research-related content for ESMO’s educational programs. Chaired by Joaquin Mateo, PI of VHIO’s Prostate Cancer Translational Research Group, the Group’s Committee also counts on the expertise of 14 other renowned experts including Joan Seoane, Co-Program Director of Preclinical & Translational Research at VHIO.