NEW YORK – It's been three years since her advanced lung cancer diagnosis, and still 54-year-old Michelle Hills can't wrap her head around the fact that her health insurance, a Cigna plan, didn't cover the next-generation sequencing biomarker test that she believes saved her life.
In 2018, after her diagnosis, Hills thought she had just six months to live. But she is still alive today with no evidence of disease — a turn of events she attributes to broad molecular tumor profiling. Testing on Foundation Medicine's NGS panel, FoundationOne CDx, identified an ALK rearrangement in Hills' tumor DNA, and based on that result, Hills' doctor prescribed the ALK-targeted drug alectinib (Genentech's Alecensa). Her debilitating cough subsided after a single dose.
Meanwhile, Hills' health insurance at the time, a Cigna preferred provider organization plan, denied coverage for the bulk of the $5,800 test. Hills, who worked in the health insurance industry before her cancer diagnosis, knew to appeal her denial, providing extensive health records so the payor would see that the test was essential and should be covered in full. But even when Hills' appeal made it to an external review organization, the denial was upheld on the grounds that the testing was "not medically necessary."
Biomarker-directed cancer treatment has improved in the years since Hills' diagnosis, and to a certain extent, so too has insurance coverage for tests that identify treatment-associated biomarkers for advanced cancers. But when it comes to comprehensive genomic profiling assays that test for hundreds of established and experimental biomarkers, the US reimbursement landscape remains vastly inconsistent, contributing to disparities in personalized cancer treatment access among patients and placing an undue burden on community oncologists.
"Comprehensive biomarker testing saved my life," Hills said. "There should be no debate between the payor and the health system about the necessity for [these tests], and the fact that there is says that there's something inherently broken in the payor system."
Medicare vs. private insurance
Since finalizing its national coverage determination for next-generation sequencing, or NGS, panels in 2018, the US Centers for Medicare & Medicaid Service, or CMS, has agreed to cover the cost of multigene testing panels for patients with advanced cancers so long as the tests are performed in CLIA-certified labs and have been approved or cleared by the US Food and Drug Administration for use as a companion diagnostic in an FDA-approved indication. The determination has been welcome news for a handful of commercial labs — Foundation Medicine among them — whose comprehensive genomic profiling tests have FDA-approved companion diagnostic indications.
Tests that don't qualify under the NCD must meet local coverage criteria stipulated by CMS' Medicare Administrative Contractors, which can be inconsistent. Importantly, the NCD has little bearing on the coverage of large NGS panels for the roughly two-thirds of the country's insured population with private or commercial plans.
"Ironically, there's good access [to comprehensive genomic profiling tests] under Medicare … they have the coding in place, it's approved, and it's paid for," said Frederick Schnell, chief medical officer of the Community Oncology Alliance, or COA, a nonprofit organization that advocates for community oncology practices and the patients they treat. "The private sector is completely the opposite. They don't have preordained benefits in this domain, and there's some significant reluctance."
Indeed, three years after CMS' NCD, patients with advanced cancer with commercial health plans are facing denials that neither they nor their providers can predict.
"Payors aren't covering big panels all the time, and it would be nearly impossible for an average patient to try to look at their plan and suss out whether it covers the level of comprehensive biomarker testing that they need," said Nikki Martin, the director of precision medicine initiatives at the lung cancer advocacy organization LUNGevity Foundation.
Oncologists' disparate experiences also reflect this inconsistency. Charu Aggarwal, a thoracic oncologist at the University of Pennsylvania, said she and her patients never have issues with insurance approvals for comprehensive biomarker testing. In contrast, Martin Dietrich, an oncologist who treats patients within the community oncology network Florida Cancer Specialists, said his Medicare patients usually receive covered testing, but he is constantly on the phone appealing denials for his commercially insured patients.
This discrepancy in coverage policies between commercial payors and Medicare may not come as a surprise. In 2018, shortly after CMS finalized the NCD, surveys suggested that commercial payors didn't necessarily agree with the broad coverage terms CMS issued in its NCD and that they would craft policies for NGS cancer panels based on their own technology assessments.
According to a 2020 Boston Healthcare Associates, or BHA, analysis of the top 20 commercial plans in the US, 55 percent of privately insured people are not covered or are only covered on a case-by-case basis for comprehensive tissue-based NGS panels that test for more than 50 genes.
Single gene vs. comprehensive testing
For Michelle Hills, alectinib wouldn't have been an option without the "comprehensive" element of FoundationOne CDx. Testing that a pulmonologist at her local Kansas City hospital ordered when Hills was diagnosed with cancer returned an "indeterminant" result for her ALK rearrangement status. Hills isn't sure but suspects she may have received a fluorescence in situ hybridization test, which can be prone to failure.
FoundationOne CDx includes 324 genes on its panel for a list price of $5,800 plus optional add-ons for biomarkers like PD-L1 expression status. However, the category of "comprehensive" NGS tests for advanced cancers comprises a diverse list of tests in terms of the depth and breadth of their analysis. Natera, for example, advertises a whole-exome and transcriptome-based approach with its Altera test, which assesses 440 "medically important genes," while Memorial Sloan Kettering's MSK-IMPACT test includes 505 genes "chosen because they play a critical role in the development and behavior of tumors."
Despite the differences in the gene sets analyzed by these tests, they all identify tumor biomarkers beyond those backed by national guidelines organizations like the National Comprehensive Cancer Network. As such, many payors question why they should pay for this extra biomarker information that they consider investigational or lacking in clinical validity and utility.
According to a 2020 analysis of payor perspectives on biomarker testing in the Journal of Managed Care & Specialty Pharmacy — for which over 70 percent of survey participants were private payors — the most important attribute for biomarker test coverage decisions was the test's ability to improve quality of life for the insured patient. The second most important attribute was the extent to which the test improved patients' life expectancies. When it comes to biomarkers without established treatment implications, data on these metrics are scant and payors aren't too interested in helping build that evidence.
"If you ask most health plans, they do not consider it their responsibility to pay for research," Michael Kolodziej, VP of the consulting firm ADVI Health, said at a recent Precision Medicine Leaders Summit webinar on the reimbursement landscape for NGS tests. The fact that Kolodziej has been hammering home this same point for years, especially while he was Aetna's medical director of oncology solutions, suggests that despite the growing list of targetable tumor markers and precision oncology treatments, insurers' perception of the value of large NGS panels hasn't evolved much.
The tension between what labs are testing for and what payors will cover is most prevalent in settings such as non-small cell lung cancer, where guidelines bodies and patient advocacy groups now recommend testing patients for tumor alterations in multiple genes. LUNGevity advocates for, at a minimum, testing for biomarkers in ALK, BRAF, EGFR, HER2, KRAS, MET, NTRK, RET, and ROS1, plus proteins such as PD-L1. "You need to have some sort of a multiplex panel to test for these [minimum] biomarkers," Martin said. "But there's a gap, because nine biomarkers on a multiplex panel … not many labs are running that kind of a test."
The problem is not lost on insurers. "Payors don't like panels," Kolodziej said at the Precision Medicine Leaders Summit. "When I was at Aetna, we were fond of saying that no patient in the history of mankind needed 350 genes sequenced. … The problem is, they still need [about] 50, and it's hard to get those 50 outside of the whole 350."
As the cost of sequencing continues to come down, some labs are doing a comprehensive test, such as whole-exome testing, reporting the genes insurers will pay for, and "throwing away the rest," said Lee Newcomer, who worked with UnitedHealthcare for over a decade but is now an independent consultant. "We're rapidly reaching a point where doing a whole panel of all the genes you need is just about the same cost as doing specific genes individually and then reporting them together," he said.
Even if some labs may be censoring investigational biomarkers in their reports to improve coverage, many oncologists argue that this additional information should be reported because it opens the door to clinical trials. Patients who test negative for established biomarkers associated with FDA-approved treatments may test positive for a variant for which a drugmaker is running a clinical trial. Testing for a broader biomarker set "may be very significant in terms of treatment decisions if not in the first line then in subsequent lines of therapy," UPenn's Aggarwal said.
There are now also biomarkers such as NTRK fusions or tumor mutational burden that allow patients with any tumor type to receive targeted treatment or immunotherapy if they are out of other options. Broader NGS panels streamline assessment of rare tumor alterations like NTRK fusions and are needed to calculate a biomarker like TMB.
Plus, in lung cancer, as with many other advanced cancers, sequential, single-gene testing is difficult, if not impossible. Patients may not have enough tissue — or time — for another biopsy.
"For a while, we got along doing single-gene testing off a menu like you would order at a restaurant," reflected COA's Schnell, who also practiced oncology for decades at Central Georgia Cancer Care. "[But] it does not give enough information back for most situations, and it takes a lot of time. These patients don't have that time. Panel testing is the only answer."
Shifting costs, coding logistics
Florida Cancer Specialists' Dietrich looks at the cost of comprehensive biomarker testing in the context of the cost of treatment. While a several-thousand-dollar bill for a comprehensive genomic test might be prohibitively high for patients, for insurers, it pales in comparison to the cost of treating a patient with the wrong therapy.
"If I give a patient immunotherapy when they have virtually a nonexistent chance of responding … the sticker [price] is about $12,000" per infusion, Dietrich said. "This is not just about selecting the right therapies but also not choosing the wrong therapies. It saves money, side effects, hospitalizations."
Many of Dietrich's commercially insured patients receive denials for tests exceeding a certain number of genes. "In Florida, one of the biggest commercial insurers is Florida Blue, and they don't pay for any panels greater than 50 genes," Dietrich said. "That basically excludes most of the multigene panels and makes it more or less impossible to have comprehensive analyses."
Florida Blue refuted that its policies only cover panels with up to 50 genes. "We do not have a limit established for the number of genes that can comprise a panel," said Ted Conklin, the payor's VP and chief medical officer of commercial business.
Florida Blue, Conklin said, will cover tests that are approvable based on "medical necessity criteria" when they are billed separately as individual tests. In cases where the tests aren't available as single-gene tests and are only offered within larger panels that contain other "experimental or investigational" biomarkers, he explained, Florida Blue will deny the panel but potentially cover it following appeals.
Stacey Brown, Foundation Medicine's senior director of payor market access, acknowledged this billing conundrum. "There is a particular billing code that describes these types of tests at less than 50 genes and then another billing code that says greater than 50 genes, and that puts this imaginary number in the payors' heads," she said.
Florida Blue receives coverage policy guidance from the BlueCross BlueShield Association, but these policies are nonbinding; member plans can make their own coverage decisions. According to an analysis published in Value Health of commercial payor policies on cancer NGS testing between 2015 and 2019, BlueCross BlueShield members were less likely to adopt positive coverage policies among 69 evaluated payors. And while coverage for genomic sequencing increased during this time, the analysis found significant variability in payors' policies.
Julia Trosman of the University of California San Francisco's Center for Translational and Policy Research on Personalized Medicine, an author on the Value Health paper, noted an important distinction. Insurers "may still be paying for these tests, but not have a formal coverage policy," she explained. "Once you cover something … it's very difficult to rescind coverage, [so] they're being very careful."
In other words, Conklin suggested that payors like Florida Blue may be open to covering broad NGS test panels following appeals even if they haven't formally written this coverage into their policies.
Burden on oncologists
Although the process can be effective, constantly appealing denials is taxing both for patients like Hills and oncologists like Dietrich.
"This takes a huge amount of time, and it is basically the physician who has to stem that," Dietrich said. "You spend 20 to 30 minutes of your day on the phone talking to somebody, and it's very challenging and disincentivizing. Even though you may be scientifically right [about the need for testing], they often tell you upfront that their guidelines don't support it no matter what you say."
He estimated that around half the patients he determines could benefit from a large NGS panel end up getting one. For those patients who are denied, Dietrich, who works in one of the larger community oncology systems in the country, can turn to an in-house pathology department for a more limited assessment.
Meanwhile, for oncologists in smaller practices with less administrative support, the time required to appeal payors' coverage denials can be prohibitive. And beyond these billing challenges, many oncologists find it challenging to interpret lengthy comprehensive genomic profiling reports. "It's very difficult for the clinical community to keep up," Schnell said. "The evolution of science to the clinic is still not where it needs to be."
This likewise adds to payor reluctance to cover testing that might lead doctors to put patients on off-label or investigational treatments based on biomarkers with scant evidence. "Payors are worried about these panels because they're afraid [that] people will prescribe drugs off-label, and in some cases off-evidence, to the detriment of the patient and to the incredible cost" to payors, ADVI's Kolodziej said at the summit. He acknowledged that even if off-label prescribing may be occurring less frequently than payors think, "these targeted therapies are not cheap."
Financial assistance
Knowing the burden that repeated payor denials can put on oncologists and their patients — and wanting reimbursement for their tests — many commercial labs like Foundation Medicine offer to appeal denials on patients' behalf.
Foundation tells customers on its website: "If your insurance company denies coverage for a Foundation Medicine test, with your consent, [we] will work to obtain coverage and pursue appeals." For its Altera test, Natera similarly offers to connect patients with coordinators who will "file appeals and pursue coverage" on their behalf.
Foundation Medicine's Brown described this service — part of the Foundation Access Program — as a way to help not only patients, but also providers who may, like Dietrich, face hours of administrative work to justify medical necessity.
"A growing number of commercial health insurers are putting the responsibility and burden on the ordering provider [to justify coverage], which I find interesting given that the ordering provider is not the entity billing for the service," Brown said, emphasizing that it is actually the lab that gets reimbursed.
According to Brown, Foundation Medicine does commonly encounter commercial payor denials, but because FoundationOne CDx has multiple FDA-approved companion diagnostic indications, overturning these denials isn't difficult. Based on claims data from January 2019 to March 2020, Foundation Medicine estimated that before financial assistance 61 percent of commercially insured patients paid zero dollars for FoundationOne CDx.
However, when the payor upholds a denial, Foundation Medicine has a need-based financial assistance program for patients who meet a certain annual household income threshold and have other extenuating circumstances. Brown did not disclose the income limit or the types of extenuating circumstances that might qualify a patient.
Foundation Medicine's assistance program ultimately saved Michelle Hills from a steep bill that she and her husband could not afford. She went back and forth with Cigna for seven months before Foundation Medicine dissolved her balance. Only after Cigna denied coverage on administrative grounds — citing prior authorization failures — and an external review upheld the denial on medical necessity grounds, did Hills turn to the lab for help.
Hills isn't sure whether Foundation Medicine succeeded in overturning Cigna's denial on her behalf or if the lab simply ate the cost. She acknowledged that not all patients in her situation would have known to call the lab, as opposed to their insurance company or doctor. But had she not made this last-ditch call to the lab, Hills would have been legally responsible for at least $3,316 (a discounted amount Hills was initially told she owed Foundation Medicine), since she signed a financial liability waiver prior to testing.
"The financial aid person said, 'Unless you sign this paperwork, we're not going to send your tumor out,'" Hills recalled. The form stipulated that Hills could be on the hook for $5,800 in the event of a denial. "When you're so desperate for something that might help you [survive], you're willing to sign anything," she said.
Limits of assistance
Tests without FDA-approved companion diagnostic indications may face added payor reluctance. An analysis of some 350 patients tested with Columbia University's in-house 467-gene Columbia Combined Cancer Panel from 2017 to 2018 revealed that three-fourths of commercial payors denied coverage. A molecular tumor board consisting of oncologists, molecular pathologists, and other members of the patient care team, meanwhile, deemed findings from these tests "clinically impactful" for 64 percent of patients.
Although the timeframe included in the analysis mostly predated CMS' 2018 NCD, Jennifer Oberg of Columbia, who co-led the study, didn't think the results would differ today. "The CMS policy is for companion diagnostics that have been given FDA approval," Oberg said. "Our test is an internal test that doesn't have that FDA indication."
But Columbia is a well-resourced academic cancer center that budgeted for insurance challenges with its CCCP test. Oberg's study guaranteed patients that, should their insurance plans deny coverage, Columbia would pay for the tests.
"We're very fortunate [that] we have funding to offset those costs," Oberg said. "Without this funding, there are threats to precision cancer medicine in that only people who could pay the out-of-pocket costs would be able to get this testing."
For the time being, commercial labs and institutions, such as Foundation and Columbia, are bridging the financial gap when patients face payor denials. But some are beginning to ask whether there is a limit to what financial assistance programs can accomplish given the rapid pace of precision oncology advancements.
"There are still resources to cover testing costs, [so] the testing companies are still being very generous with picking up costs not covered by insurance," LUNGevity's Martin said. "[But] I don't think they're going to be able to continue that forever."
Oberg echoed this concern. "Right now, we're not so worried [at Columbia], but we have to think about the future of sustaining these testing programs and being able to push precision medicine forward."
Enough evidence?
Labs and oncologists are hoping that payors' willingness to cover broad NGS panels will increase in step with a growing body of evidence showing that these tests can match patients to the right therapies and increase patients' survival with minimal added cost to payors. In one such study of patients who underwent comprehensive genomic profiling at the MD Anderson Cancer Center, for instance, patients matched to therapy based on the testing had longer overall survival than those who received unmatched therapy. The researchers reported a "manageable" incremental cost increase associated with the genomic profiling, but they said this was a result of the longer duration of therapy rather than higher monthly drug costs.
However, as the cancer genetic testing landscape gets more crowded, insurers are spending more. The Office of Inspector General reported last year that Medicare spending on lab tests was $7.7 billion in 2019, up $93 million from 2018. Although payment rates year over year were lower for most lab tests, spending on genetic tests increased by $390 million to $1.36 billion in 2019. Notably, in this segment, Medicare spending on molecular tests (the category that comprises many cancer NGS panels) increased by 74 percent from 2018 to 2019 to $849 million.
Amid growing spending, payors are contracting with third-party laboratory benefit management companies like EviCore, which conduct technology assessments and craft guidelines based on the available evidence that inform payors' coverage policies. According to a BHA analysis, eight of the top 30 US commercial plans use EviCore guidelines to drive coverage decisions, accounting for about 18 percent of covered lives among those plans.
From the payors' perspective, groups like EviCore help control spending on genetic tests, ensuring it is "medically necessary." But labs, providers, and patients facing coverage denials don't necessarily view lab benefits managers as being on their side.
"In the cancer world, [EviCore] is referred to as 'nevercore,'" said Hills, who noted that Cigna, which administered her plan, contracts with EviCore to inform coverage decisions. "It seems like EviCore's initial reaction is to delay, delay, delay, and then deny." EviCore did not respond to a request for comment.
Ultimately, some believe that the only solution to the difficult reimbursement environment is stronger evidence. "We're going to have to show that [these tests] result in people living longer and getting better outcomes," Schnell said. "[This will] require the creation of value-based outcomes data, which has trickled in for a while but is coming a little more heavily now."
While many umbrella trials and real-world studies are also underway assessing the value of broad NGS, the emerging data to date haven't swayed payors to radically change their stance on covering these technologies. "I feel like we're in this frickin' time warp, and it drives me nuts," ADVI's Kolodziej said, lamenting what he sees as a dearth of new evidence that has translated into payors' rewriting coverage policy. "I started at Aetna almost eight years ago, and I feel like we haven't gone anywhere except adding a little bit here, a little bit there."
Even if better evidence is forthcoming, as Schnell believes it is, and commercial payor coverage subsequently improves, tissue-based NGS panels won't be all payors have to worry about. Oncologists are adding more tests to their precision oncology toolboxes and the field is already shifting its attention to NGS liquid biopsy testing in the wake of Guardant Health and Foundation garnering FDA approval for their tests last year.
A recent survey of payors' attitudes about liquid biopsy test coverage identified some of the same concerns that have riddled the tissue NGS space. "Private payors vary greatly in how they develop and structure their coverage policies," the paper's authors wrote, adding that "such variation … may make it difficult for patients and providers to understand relevant policies."
UCSF's Trosman wondered whether the path to widespread coverage for liquid biopsy tests might be more streamlined now that payors, providers, and labs have all learned from tissue NGS panels. "All technologies have their own life cycles, and so too will NGS tumor sequencing," Trosman said. "The question is, are we going to at least have widespread coverage by the time new technologies start emerging and we need to start considering those? Are the new technology and payor coverage cycles at all in sync, or are we going to get more and more out of sync?"