CHICAGO — Three prototype sequencing assays designed to identify cancer-specific cell-free DNA signals were effective in detecting early-stage lung cancer, according to preliminary findings from the Circulating Cell-free Genome Atlas study.
“I think this is one of those studies that is going to have a huge impact,” Hossein Borghaei, DO, MS, division chief of thoracic medical oncology at Fox Chase Cancer Center, told HemOnc Today. “We are talking about the potential development of a blood-based assay.”
During a presentation at ASCO, Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, reviewed data on the three sequencing assays, which were used to test 2,800 blood samples from 118 patients with lung cancer (85% ever-smokers) and 561 controls without cancer (43% ever-smokers) who are enrolled in the ongoing Circulating Cell-free Genome Atlas (CCGA) study. The assays include a targeted sequencing assay, which was used to detect 507 somatic mutations at 60,000X depth; a whole-genome sequencing assay that was used to detect somatic gene copy number changes at 30X depth; and an assay for whole-genome bisulfite sequencing of cell-free DNA, which was used to detect epigenetic changes at 30X depth.
Geoffrey R. Oxnard
“This is not cancer genotyping, which is what we all do in our practice today where we look for a key mutation in the blood and use that to start targeted therapy,” Oxnard said. “This is different. Cancer detection requires a broad approach looking for any cancer signal within the blood. We think this could address an unmet medical need.”
The assays detected cancer across a range of stages, histologies and populations, including smokers and nonsmokers, with low rates of false-positive results, according to Oxnard. The biological signal of lung cancer was stronger in patients with more advanced disease. However, Oxnard said the assays “definitely have feasible detection” for early-stage lung cancer. Each of the assays, he reported, identified approximately 50% of early-stage curable lung cancers and 90% of advanced lung cancer.
More than half of somatic mutations found in blood samples were obtained from white blood cells, not tumors, which is consistent with clonal hematopoiesis, according to Oxnard. Therefore, it will be important to account for white blood cell mutations like clonal hematopoiesis when developing a blood test for early cancer detection, he said.
Borghaei noted that the sensitivities of the assays were not as high as he would have liked them to be. Nevertheless, he said the availability of a blood-based assay for early-stage lung cancer could have a positive impact on screening uptake, similar to what was seen with prostate-specific antigen (PSA) screening.
“Whether you’re for it or against it, a lot of men are getting PSA screening,” Borghaei said. “So if we can get to a point where we have a blood-based assay, perhaps there will be a better uptake in the general population because a blood test is conceived as being a little easier to do.”
Cell-free DNA-based sequencing will be further investigated in the CCHA trial as well as the ongoing STRIVE trial, according to Oxnard. Borghaei said it will be important to examine this testing approach during prospective studies before it can be used as standard care.
“Even with CT-based screening, we have a lot of false positives,” he said. “If you have something like this in conjunction with a low-dose CT, perhaps you can reduce your false-positive and false-negative rates, or have a little more comfort with saying, ‘This test is positive, and your CT looks suspicious, so I think you probably have lung cancer.’ But again, we have to go where the science is, and hopefully down the road we will have additional information to guide that way of treatment.” – by Stephanie Viguers
Oxnard GR, et al. Abstract LBA8501. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Borghaei reports no relevant financial disclosures.