NEW YORK – Merely a hypothesis a few years ago, the use of circulating tumor DNA or liquid biopsy technologies to guide treatment for early-stage cancer patients continued to surge in 2023, as clinical testing, research efforts, investments, and legal scrutiny all expanded.
With growing acceptance from payors, pioneers in the space are facing the new year less as promoters of a new technology and more as an established feature of the care pathway for patients receiving curative-intent cancer surgeries.
In years past, Medicare had agreed to reimburse minimal residual disease (MRD) testing in colorectal cancer, which was the first clinical niche that most MRD innovators explored. But two leading companies, Natera and NeoGenomics, made an important next step in 2023, winning local coverage determinations through the MolDx program for a newer indication, early-stage breast cancer.
As a large market with a well-established screening paradigm that regularly identifies small, surgically treatable tumors, breast cancer has become a target for a majority of the commercial firms pursuing MRD and the focus of much ongoing research, but important studies also continue to read out for the more established colorectal cancer indication, either shoring up utility data or building expanded use cases for specific patient groups or testing timepoints.
Last January, Natera published new data on the added value of MRD testing after initial colorectal cancer surgery to guide the use of adjuvant chemotherapy. According to Alexy Aleshin, the firm's chief medical officer, the CIRCULATE-Japan trial results suggest that there could be a fundamental shift in how early-stage colorectal cancers are staged with tumors defined based on their MRD status rather than the clinical features currently used.
The data demonstrated that not all risk is being captured by current staging methods. In other words, a stage II patient, whose physician might otherwise recommend against chemo based on current guidelines, could still be MRD positive, with a higher risk of recurrence and a strong likelihood that adjuvant treatment would benefit them.
In the upcoming year, the field is likely to see even more advancement in new indications, like lung cancer, bladder cancer, melanoma, and even potentially in rare tumors like sarcomas.
Personalis, Natera, and NeoGenomics have all cited plans to build evidence for their tests in melanoma, as tools to monitor patient responses to immunotherapy, which can be complicated by a unique factor called pseudoprogression in which tumors appear to be progressing based on imaging and clinical signs, but are actually poised to respond.
Bladder cancer is another emerging target that saw progress in 2023. NeoGenomics published a study in February showing that its Radar assays could predict patient outcomes, with the potential to help inform the choice to perform or avoid cystectomy, an aggressive surgery that removes the patient's bladder.
Natera said in October that it had submitted the first premarket application module to the US Food and Drug Administration for its Signatera MRD technology as a companion diagnostic for patients with muscle-invasive bladder cancer.
Some newer entrants to the field, meanwhile, have focused more on lung cancer. Personalis, which distinguishes its MRD approach by using upfront whole-genome sequencing rather than exome or targeted sequencing to develop patient-personalized blood test panels, said recently that lung cancer could be the first indication that it takes to Medicare.
The firm highlighted data this October from the TRACERx lung cancer study, which showed that the company's tests performed better than other circulating tumor DNA assays in tracking patterns of response and tumor evolution.
Prior to adopting Personalis' NeXT Personal platform last year, TRACERx had employed a succession of other technologies, including Natera's Signatera assays and Inivata's Radar technology.
With applications expanding in what thought leaders have estimated is a barely penetrated, up-to-$20 billion market, commercial and investment attention accelerated over the course of 2023. Notably during the year, lab giant Quest Diagnostics announced it would acquire emerging MRD firm Haystack Oncology.
During a discussion at the European Society for Medical Oncology congress in October, Federica Di Nicolantonio, an associate professor at the University of Turin School of Medicine, estimated there are as many as 13 different MRD assays utilizing a tumor-informed strategy. These are joined by others, like Guardant Health's Guardant Reveal, that use fixed, tumor-agnostic panels.
Among commercial milestones, Invitae published some of the first data on its Personalized Cancer Monitoring test, which it netted in its acquisition of ArcherDX, and Foundation Medicine made its MRD debut in October after highlighting a study conducted with Natera.
Exact Sciences also announced that it would be joining the MRD race with the launch this winter of a tumor-informed, patient-personalized assay platform called OncoDetect. And C2i Genomics said in April that it had begun a soft-launch for its whole-genome sequencing based MRD kits in Europe.
Reflecting increased commercial fervor, many companies are involved in patent and other litigation against one another, some of which came to a head during 2023. Personalis expanded its lawsuit against newer entrant Foresight Diagnostics in June to cover three additional patents. Foresight, which launched in 2022, has taken a whole-genome-based approach that echoes the comprehensive scheme that Personalis pursued as a distinguishing factor from other tumor-informed tests on the market.
Natera, one of the first companies to launch an MRD service, has ongoing suits against a slew of companies in the space, with two big wins in 2023, including a decision by a jury in the US District Court for the District of Delaware awarding it $19.4 million in damages for royalties and lost profits in a patent lawsuit against Invitae and ArcherDx, followed by an injunction against the same firms, and a second injunction against NeoGenomics, both in December.
Invitae and NeoGenomics are now faced with either reversing the injunctions or altering their assays so that they don't infringe the Natera patents in question.
Although experts have said the MRD market remains barely penetrated, it also appeared that 2023 was a turning point for commercial acceleration. Discussing its third quarter financial results in November, Natera said it performed approximately 89,000 oncology tests, up 68 percent from 53,000 tests in the third quarter of 2022. About 81,000 of these were the firm's Signatera MRD assay, a volume boost of 85 percent compared to the prior-year period.
Personalis cut its sales runway down significantly by partnering with established cancer testing firm Tempus to market and requisition its MRD tests.
Private payors also began to back MRD during the year, with notable wins for Guardant Health with Geisinger Health Plan and Blue Cross Blue Shield of Louisiana.