NEW YORK (GenomeWeb) – Molecular diagnostics firm Biodesix is hoping quick turnaround time and targeted analysis will help drive up take of its GeneStrat non-small cell lung cancer mutation test in the community setting.
In a study published this week in the Journal of Molecular Diagnostics, researchers from Biodesix and Bio-Rad, which makes the droplet digital PCR platform on which the test is run, found that for 94 percent of 1,643 GeneStrat test performed in its CLIA facility, results were available within 72 hours.
Gary Pestano, Biodesix's vice president of product development and operations and senior author on the paper, said that the company has maintained this turnaround time as test volume has grown. He said that Biodesix has run roughly 7,000 GeneStrat tests since launching the product in 2015.
Pestano added that the company is working to further lower turnaround time, primarily by automating the entire test workflow. The goal, he said, is to return results on 90 percent or more of its GeneStrat tests within 48 hours. Currently, he said, the company manages 48-hour turnaround for roughly 70 percent of GeneStrat tests.
Rapid turnaround is one of the key test features Biodesix is banking on as it tries to position GeneStrat as a competitor or complement to both blood-based next-generation sequencing assays from firms like Guardant Health and Foundation Medicine and tissue-based testing, Pestano said.
"Turnaround time was the first sort of laying down of the gauntlet by our commercial team," he said. "They said that this product would be competitive if we could do this."
According to statistics cited in the JMD study, roughly 80 percent of cancer patients do not have genetic mutation results at their first oncology consultation, and up to 25 percent of patients start treatment before they have mutation testing results.
Pestano suggested that this problem was particularly acute in the community setting, which Biodesix has targeted as the main market for the test.
"In the academic setting there is a lot more readily available [molecular testing]," said Hestia Mellert, Biodesix's director of molecular development and first author on the JMD study. "But we definitely see a need in the community setting for products like this."
She noted that in addition to turnaround time, the company paid attention to details, particularly around sample collection, that would make the test amenable to ordering in the community setting.
"We developed it specifically so a specimen collection kit can go out into the field to these small physician networks, and they just have to do the blood draw and they can ship it very easily back to us," Mellert said. "With things like the blood collection tubes, we are very careful about the kind of collection we do and what tubes we use, so we can ship it at ambient temperature and maintain the integrity of the sample."
The initial version of GeneStrat looked at the EGFR, KRAS, ALK, and BRAF genes, and the company has since added testing for ROS1 and RET mutations and EML4-ALK fusions. In the JMD study, the researchers reported on clinical validation of the test which examined 219 NSCLC patients and 30 controls and established sensitivity and specificity for each variant ranging from 78.6 percent to 100 percent and 94.2 percent to 100 percent, respectively.
Of the 1,643 GeneStrat tests run out of Biodesix's CLIA lab that the study reported on, 10.5 percent were positive for mutations for EGFR sensitizing, 13.8 percent were positive for mutations for EGFR resistance, 13.2 percent were positive for mutations in KRAS, and 2 percent were positive for EML4-ALK fusions.
NGS-based liquid biopsies typically look at a wider range of variants than the GeneStrat test, but Mellert said the company believed the test's more limited panel could prove an advantage, as the variants included have all been demonstrated by past research to have clinical utility.
"The feedback we have gotten from physicians is that for mutation testing they don't really want a large panel," she said. "What they are looking for is an approach that gives them actionable information."
"The reason we are doing these targeted mutations is because their clinical utility has been established," Pestano added. "Therapies exist for virtually all of the variants we test for."
Blood-based tests like GeneStrat are typically less sensitive than tissue-based testing, but, Pestano said, the hope is that the test's rapid turnaround time will encourage physicians to use it as a rapid initial test, even if they plan to follow up with a tissue biopsy.
Tissue-based testing can be quite rapid, but its turnaround time can vary depending on the logistics of sample collection and handling, and the assays performed, he said.
"You do a [hematoxylin and eosin stain] first and work up what that looks like," he said. "Then you do a battery of IHC tests, and then you reflex, if needed to molecular tests, like FISH, if you have to and then PCR or qPCR test, which also adds time."
"What we are seeing our physicians doing is using our liquid biopsy first because it has such a fast turnaround time, and if they get a positive, then they can act on that," Mellert said. "If they get a negative result, then a lot of times what they do is wait for the mutation test in the tissue to either confirm that negative or verify that there was a mutation in that section of tissue."
"In the frontline setting it can be anywhere from 30 percent and up of patients who may not have a tissue biopsy result at the time of initial presentation," Pestano said. "The patient is sitting there for two weeks or more with really no action taken. This is where liquid biopsy in general is finding a niche and where we have found a place where we can plug in liquid biopsy and get results to the patients in the community very rapidly."
GeneStrat is part of Biodesix's larger "Lung Reflex" product, a portfolio of multi-omic blood-based tests for NSCLC that includes its flagship product Veristrat, a proteomic test for assessing whether patients are likely to respond to EGFR inhibitors.
Biodesix launched GeneStrat in large part to help drive adoption of Veristrat, the idea being that oncologists would use the PCR test for initial mutation testing and then use Veristrat for their patients with wildtype or indeterminate results to determine if they were good candidates for an EGFR inhibitor.
The company is now developing another proteomic test for assessing whether patients deemed by Veristrat unlikely to benefit from EGFR inhibitors might respond to immunotherapy. It plans to launch that test later this year.