Kate Johnson

June 08, 2017

CHICAGO — While the idea of using a drop of blood to detect an occult cancer is still elusive, use of so-called liquid biopsies for cancer screening is at least a little closer to reality with the development of a new high-intensity genomic sequencing approach outlined here at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.

A new test (under development by Grail Inc) highlighted in the ASCO press program uses high-intensity sequencing on circulating tumor DNA (ctDNA). It offers "an unprecedented combination of breadth and depth," surveying 508 genes and yielding about 100 times more data than other currently used approaches, said investigator Pedram Razavi, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York City.

Dr Razavi presented results from a concordance study in 124 patients with metastatic cancer, which showed that the new test picked up 89% of genetic changes that had been identified with regular tumor biopsy and 76% of "actionable" mutations that could be treated with targeted therapy.

"Our findings show that high-intensity circulating tumor DNA sequencing is possible and may provide invaluable information for clinical decision-making, potentially without any need for tumor tissue samples," Dr Razavi commented.

"The ultimate goal would be detection of cancer in early, treatable stages," he said during a press conference here.

Medscape Medical News approached Philip Mack, PhD, professor and director of molecular pharmacology at the University of California Davis Comprehensive Cancer Center, for comment. He was not involved in this study, but at last year's ASCO meeting, he presented a study about the Guardant360 liquid biopsy assay.

"An advantage of this approach is the breadth of potential data obtainable from a simple blood draw," Dr Mack told Medscape Medical News.

"Simultaneous analysis of over 500 cancer-associated genes from ctDNA could provide nuanced information on companion mutations and tumor evolution, which could help fuel therapeutic development in cancer research."

However, Dr Mack added: "Whether this or other approaches can be used for early detection of cancer remains to be seen."

ASCO experts also acknowledged that this approach is still far from reality.

 While the data are "an important step forward," according to ASCO expert John Heymach, MD, PhD, "we are a long way from using liquid biopsies for detecting cancers," cautioned Sumanta Kumar Pal, MD, another ASCO expert at the press conference.

"This field is moving very rapidly and ctDNA assays have already entered the clinic, but there are still many uncertainties, so this is always a situation where one can run into trouble," warned Maximilian Diehn, MD, PhD, from Stanford Cancer Institute, during a liquid biopsy educational session at the meeting.

Although a few ctDNA assays are available for clinical use in the United States (cobas, Roche) and Europe (therascreen, Qiagen; cobas; OncoBEAM, Sysmex), with many potential applications, screening for cancer detection is still not one of them, he said.

"Screening is one of the most exciting and high-profile applications, but we are not there yet, and screening should not be done with ctDNA assays outside of clinical trials," he said.

Dr Diehn serves on a joint ASCO and College of American Pathologists group working on a joint position statement on ctDNA-based liquid biopsies.

"The goal of this to ensure that clinical use of ctDNA assays is supported by adequate evidence, including analytical validity, clinical validity, and utility," he said, adding that the final draft should be available by the end of this year.

"It will not be a formal practice guideline because the data are just not there yet — that will come later," he said.

This study was funded in part by GRAIL Inc. Dr. Razavi disclosed Research Funding (Institutional) from GRAIL. Dr Heymach disclosed stock and other ownership interests with Bio-Tree, Cardinal Spine; consulting or advisory roles with AbbVie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, Oncomed, Synta; and research funding (institutional) from AstraZeneca. Dr Pal disclosed honoraria from Astellas Pharma, Medivation, Novartis; consulting or advisory roles with Astellas Pharma, Aveo, Bristol-Myers Squibb, Exelixis, Genentech, Myriad Pharmaceuticals, Novartis, Pfizer; and research funding from Medivation.

American Society of Clinical Oncology (ASCO) 2017 Annual Meeting. Abstract LBA11516. Presented June 3, 2017.

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