NEW YORK – In an effort to help more advanced cancer patients receive the comprehensive genomic profiling that professional guidelines increasingly recommend, liquid biopsy pioneer Guardant Health said last month that it is launching a tumor tissue sequencing test.
The move is somewhat surprising considering Guardant's efforts over the last half decade to prove to the oncology community that its blood-based tests could provide equally reliable and valuable results as tissue-based sequencing panels, and its more recent effort to promote the upfront use of liquid biopsy over tissue sequencing.
According to Guardant CEO Helmy Eltoukhy, the company has debated offering tissue testing since its inception, but in years past had felt its resources were best spent on breaking new ground.
"We've always wanted to be focused as a company on the areas that move the needle the most from a patient care perspective," he said.
Now, with recent regulatory and developmental milestones under its belt, the firm has decided to refocus on improving uptake of genomic profiling across the oncology community.
"We've gotten to a point now where we have FDA approval for Guardant360 and it's by far the leading liquid biopsy, we're launching GuardantReveal this quarter so the recurrence monitoring goal is just about to be ticked off, and we're racing down the finish line with our ECLIPSE trial [with the expectation] that we will have the first FDA-approved liquid biopsy for screening, as well," Eltoukhy said.
In this sense, the firm has "made good" on its promise of opening up and addressing multiple areas of the highest unmet need first, he added.
But as Guardant has been working to innovate, more established tools like genomic profiling of tumor tissue are still only reaching a fraction of eligible patients, he said.
"We kind of took a step back to look at … these 700,000 patients that need frontline genomic testing and we found that we are not very happy with how tissue offerings have progressed in that time," Eltoukhy said.
He argued that one of the main challenges is that at least some of the available tissue tests have "done a disservice to frontline testing," since they have turnaround times of three to four weeks, when doctors want to put a metastatic cancer patient on a treatment within a week or two.
This has left oncologists feeling that they are better served putting patients on chemotherapy or immunotherapy drugs that don't require knowledge of tumor genomics, he said.
According to Eltoukhy, Guardant frequently sees cases of patients who are on the cusp of being referred to hospice when their tumors finally get genotyped. "We find an EGFR mutation … and on the one hand, it's great that they [can then] get on a targeted therapy," he said, but it's bittersweet that they didn't get access to this treatment at diagnosis or soon after.
Paul Bunn, a professor of medical oncology at the University of Colorado, echoed this, saying that for tumor types like non-small cell lung cancer where there are multiple targeted agents approved that can significantly affect patient outcomes and quality of life, all individuals should be getting next-gen sequencing-based tumor profiling. Part of the reason they don't is due to the turnaround time of testing and taking the tissue biopsy itself.
Meanwhile, apart from the prospect of patients worsening on standard treatment when they could have benefitted from a targeted agent, Bunn said it's also becoming evident that the order of different drugs might make a difference. In particular, for NSCLC patients, upfront treatment with an immune checkpoint inhibitor can lead to problematic side effects when patients are later treated with a tyrosine kinase inhibitor based on genotyping results.
In years past, Guardant has focused on emphasizing its blood-first model as the future of standard of care solid tumor assessment and the solution to lagging clinical implementation of comprehensive genomic testing. But Eltoukhy said that the company recognizes that tissue sequencing is still going to be a part of the upfront picture at least for the near future, whether for biomarkers that require tissues to be analyzed or as a preference for certain segments of the oncology community who are sensitive to the reality that tissue is still considered the closest source of a tumor's "true" genomic profile.
"We [believe] we could have a real opportunity here to take the reins ourselves in terms of better catalyzing this market if we had our own tissue solution," Eltoukhy said.
Razelle Kurzrock, director of the Center for Personalized Cancer Therapy at the University of California, San Diego, said in an email that many things play into advanced cancer patients' access to genomics, including physician skepticism, financial or payor challenges, and disparities in healthcare, though turnaround time and sample adequacy are also critical factors.
"Each one needs to be addressed," she said, but certainly having more tests and more companies competing with one another is one way cost and technical limitation barriers can be tackled.
Guardant isn't yet disclosing the exact makeup of the new tissue assay it will be launching beyond that it will include all guideline-recommended content, as well as MSI and TMB assessments.
And although it hasn't described the technological specifics of its assay, Guardant believes it can be competitive against existing players in the market on several fronts when it launches later this year. For one, the firm believes it can translate the shorter turnaround times it boasts for liquid samples to tumor tissue sequencing, through the automation and streamlining of sample flow it has developed in its years of blood-based testing.
Tissue sequencing from market leaders like Foundation Medicine takes about two weeks from when a sample is received by the company to when results are returned. In its liquid biopsy testing, Guardant currently boasts a five-day average turnaround, but Eltoukhy did not say how fast it expects to be able to analyze tissue samples.
He said Guardant also believes that being able to market a tissue and blood-based sequencing assay pair, like competitors such as Foundation Medicine, helps create a sense of comprehensiveness that the company hopes can persuade more oncologists to make genomic profiling a part of their standard practice.
A final advantage, he argued, is that Guardant has had to work hard to make its liquid biopsy platform work on small amounts of DNA, something that can be a challenge in tissue sequencing. "There are a lot of [biopsy] specimens where there is too little DNA and high [assay] failure rates. And so that's another added benefit that we can bring to bear with our technology," Eltoukhy said.
Bunn agreed that the timelines for current send-out tissue testing can indeed stretch into multiple weeks. But the launch of faster send-out options isn't the only solution. Growing the base of disseminated, in-house hospital DNA sequencing programs could also help.
"At the University of Colorado we have a local lab and it gets [results] back in 10 or 12 days" at a lower cost than send-out services, Bunn said. "Cost is probably as big an issue as turnaround time. And the cost is not just the molecular testing, it's also the biopsies themselves," he added.
With both tissue testing and liquid biopsy available, clinicians are also now grappling with new questions about optimization and cost effectiveness, Bunn added.
For example, he said, if blood-based testing is regularly ordered first and can be returned in a little as five days, perhaps costly tissue biopsies should be held off altogether until results come back, and only performed if the liquid biopsy is negative.
Eltoukhy said Guardant is confident that marketing tissue sequencing will not dilute the company's messaging around the non-inferiority and added value of blood-based genotyping. The goal is to "allow each option to shine," keeping liquid biopsy front and center and providing tissue testing as a safety net.
Although its expected that most metastatic patients will be getting comprehensive testing in the frontline setting at some point in the future, what Guardant wants is to help accelerate that adoption.
"There's just no excuse for a patient not to be matched to an FDA-approved drug that can double their life expectancy,"Eltoukhy said.