Charles Ryan, MD
The booming field of research on blood tests for cancer has drawn billions in venture capital funding and raised the hopes of doctors and patients for a new era of detection and treatment. A profusion of so-called “liquid biopsy” tests that extract circulating tumor cells (CTCs), cell-free DNA (cfDNA or ctDNA), or exosomes from blood and urine are under investigation at research institutions and startup firms, and in some cases are already being used to supplement or replace traditional biopsies.
But although oncologists are wowed by the promise of easily monitoring patients for recurrence and treatment response, or even diagnosing disease via a simple blood draw, they note that liquid biopsy products are still not widely used. Much research remains to be done to identify clinically relevant tests and gauge the impact on patient outcomes, they say.
Experts also warn against overselling the promise of unproven technologies to patients and the general public. The FDA is watching liquid biopsy development and the genetic testing industry closely. In September the agency warned Pathway Genomics about its CancerIntercept Detect blood test for cancer biomarkers, which lacks FDA approval but is marketed directly to consumers. The company ships blood collection tubes—considered a “medical device” and subject to FDA regulations—for use in the test, and the test’s effectiveness has not been demonstrated, the agency said. “We believe you are offering a high risk test that has not received adequate clinical validation and may harm the public health,” the FDA wrote in a letter to Pathway.
The company responded that physicians are involved in ordering and reviewing the test, and said CancerIntercept Detect is a laboratory developed test or LDT, which is regulated by The Centers for Medicare & Medicaid Services rather than the FDA.
“The technology is important and impressive, but it’s the application of that technology that has become more difficult,” said J. Leonard Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society, of liquid biopsies generally. “We have to be so careful about how we represent this technology and these opportunities to our patients. There’s one researcher who said in a corporate publication that this was going to help cure breast cancer. Well, it may help cure breast cancer. But that is in the distance. That is not today.”
The FDA recently proposed extending the regulations on medical device manufacturers to many LDTs, stoking industry concerns that the rules would be burdensome and stifle innovation. Lichtenfeld said he expects more clarity on LDT regulation sometime this year.
Meanwhile, research and development continues and the demand for liquid biopsies is expanding rapidly. The global market totaled $1.5 billion last year and cancer testing represented the fastest growing subsector, reaching $415 million in 2015 and projected to increase to $1.9 billion in 2020, according to a report by BCC Research.
Janssen, whose 12-year-old Cellsearch system is the only FDA-approved CTC test, says it is used in more than 25 NCI-designated cancer centers. Guardant Health, a leading cell-free DNA testing company, said 2000 US oncologists and 20,000 patients use its services annually. Insight Pharma Reports has identified 33 companies that are developing liquid biopsy products, eight of which have particularly promising products.
Despite all that activity, CTC and cfDNA tests still do not fit into the routine practice of oncology, Lichtenfeld said. In response to a query, the Community Oncology Alliance was able to identify only one member practice, Genesis Cancer Center in Hot Springs, Arkansas, that uses them regularly. Several years ago the four-physician practice took the highly unusual step of purchasing its own Cellsearch system, said Genesis oncologist Stephen Divers, MD. He recalled that his Medicare carrier was initially confused, having never been asked to cover the costs of such a machine.
Genesis conducted thousands of tests over two years, including several as part of a University of Arkansas trial on colon cancer recurrence, but Divers found that many patients had too few CTCs to make the system useful and he stopped using it. Two years ago the practice tried out a different kind of liquid biopsy, joining a pilot trial of Guardant cfDNA testing. It has since become a regular part of the practice’s toolkit.
Divers said he recently used the Guardant test for a lung cancer survivor with recurrence in her lymph nodes who stopped responding to erlotinib (Tarceva). He suspected a T790 mutation, but he was not sure if he could successfully biopsy her tumor, which was situated between the aorta and pulmonary artery.
She had also previously undergone lung surgery. Instead of performing another biopsy, he reviewed her CT scan, drew blood, confirmed the mutation, and switched her to osimertinib (Tagrisso), a newer oral EGFR inhibitor.