ESMO recommends use of NGS for advanced cancers

By Samantha Black, PhD, The Science Advisory Board editor in chief

August 25, 2020 -- The European Society for Medical Oncology (ESMO) released its first recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers. The guidance was published in the Annals of Oncology on August 25.

NGS allows for the sequencing of large quantities of nucleotides in a short time frame at an affordable cost. Recent advancements in technology have moved NGS into the clinic, where it is being more frequently used to guide treatment decisions thanks to its ability to sequence long and complex genes or multiple genes in tumor samples. The goal is to identify driver genes and/or targetable alterations in cancers.

"Although NGS has been widely implemented, until now there were no recommendations from scientific societies on how to use this technique in daily clinical practice to profile metastatic cancers," said first author Dr. Fernanda Mosele, medical oncologist at Gustave Roussy in Villejuif, France.

In the paper, the organization proposes three levels of recommendations for the routine use of NGS on tumor samples in advanced nonsquamous non-small cell lung cancers (NSCLCs), prostate cancers, ovarian cancers, and cholangiocarcinoma.

"These are the first recommendations from a scientific society about the use of NGS," Mosele explained. "Our intent is that they will unify decision-making about how NGS should be used for patients with metastatic cancer."

The ESMO Translational Research and Precision Medicine Working Group developed the recommendations based on the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) ranking for genomic alterations occurring in the eight cancers responsible for the most deaths worldwide. For each tumor type, the experts used the ESCAT ranking and prevalence of alterations to calculate the number of patients who would need to be tested with NGS to identify one patient who could be matched to an effective drug in daily practice.

The first recommendation level is from a public health perspective. The organization recommends the use of RNA-based NGS, or DNA-based NGS designed to detect fusions in patients with advanced nonsquamous NSCLC. For prostate cancers, large panels should only be performed on a case-by-case basis, given that they are unlikely to be cost-effective but could be useful to assess mutational status of BRCA1/2.

In the case of cholangiocarcinoma, multigene NGS could be used to detect level I actional alterations. In ovarian cancers where BRCA1/2 somatic mutations have been associated with increased benefit of poly (ADP-ribose) polymerase inhibitors, the use of multigene NGS is justified.

Large NGS panels could point to expensive drugs outside of their approved indications.

The second recommendation level is from the perspective of academic clinical research centers. The ESMO recommends that clinical research centers perform multigene sequencing for molecular screening programs to increase access to drugs and speed up clinical research. Economic evaluations in parallel to clinical trials should also be implemented to foster evidence in this field to increase access to innovation for patients.

And the last level of recommendation is from the individual patient. According to the authors, using a large panel of genes may only infrequently lead to clinically meaningful results, compared to small panels or standard testing. Therefore, beyond the four cancers listed in the paper -- given that there are no extra costs for the public healthcare system and if patients are informed of the low likelihood of benefit -- doctors and patients may still decide to order large panels.

"This recommendation acknowledges that a small number of patients could benefit from a drug because they have a rare mutation," said co-author Dr. Joaquin Mateo, chair of the working group and a researcher at Vall d'Hebron Institute of Oncology in Barcelona, Spain. "When an alteration is uncommon, it will be difficult to gather enough patients in research studies to generate the evidence necessary for using NGS. So, beyond the cancers in which everyone should receive NGS, there is room for physicians and patients to discuss the pros and cons of ordering these tests."

The authors noted that the recommendations will need to be updated on a regular basis as new data emerge for novel therapies across different cancers.

"This paper highlights how difficult it is to move precision medicine approaches from research into everyday clinical practice," Mateo said. "For example, we need to address the issue of rare cancer subtypes or biomarkers more common in specific populations that may be underrepresented. ESMO is committed to bridging the gap between research and practice by providing evidence-based guidance on the use of NGS that leads to equal access to the best care for all patients with cancer."

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