Treatments aimed at certain mutations have proliferated and moved upstream to earlier-stage lung cancers. But there are many questions about insurance coverage and which tests to use to identify the biomarkers that help guide treatment.
In lung cancer especially, the ability to identify genomic alterations in patients’ tissue or blood samples has opened the door for more widespread adoption of targeted and immunotherapies, says Luca Quagliata, Ph.D., BCMAS, vice president and global head of medical affairs at Thermo Fisher Scientific, a healthcare tech and testing company headquartered in suburban Boston. Therapies tailored to lung cancers with certain genomic signatures have replaced chemotherapy as a first-line treatment for patients with lung cancer, he says, and advances in biomarker testing have decreased the turnaround time for results.
“We are no longer trying to convince people that genomic testing is valuable in lung cancer,” Quagliata says. “There is enough evidence to show its clinical utility.”
Quagliata also says testing has shifted from being done almost exclusively for patients with late-stage cancer to those with cancers diagnosed at an early stage as more targeted treatments prove to be effective in patients who are treated with surgery. This move “upstream” means fewer patients need to be treated with chemotherapy and radiation. Quagliata is also upbeat about the future of liquid biopsies, which detect early signs of cancer in blood samples rather than on samples of tissue from site of the tumor. “The value of liquid biopsy is that it is much less invasive to patients and has a simpler laboratory workflow when compared to acquiring and testing tissue samples,” Quagliata says. “ Thermo Fisher has a liquid biopsy product.
Raymond U. Osarogiagbon, M.D., FACP, the director of the multidisciplinary thoracic oncology program at the Baptist Cancer Center in Memphis, Tennessee, notes that as recently as 2012, almost half of advanced nonsquamous non-small cell lung cancers (NSCLCs) had no known biomarker that could be targeted for treatment. Now only about 1 in 10 of such cancers lacks biomarkers, he says, and the list of biomarkers — typically, a mutated gene — for which there are FDA-approved has grown from just two treatments to 10.
Targeted therapy for certain subsets of biomarker-specified lung cancer significantly improve survival. But Osarogiagbon says use of targeted therapy in patients lacking the specific target can cause harm. If the cancer doesn’t have the target, a targeted therapy is tantamount to no treatment. The longer that continues, the greater the harm. Therefore, biomarker testing is a key, fundamental part of successful targeted therapy. Several of the biomarker-delineated subsets of lung cancer are infrequent, occurring in fewer than 5% of all patients, notes Osargiagbon. “There is no clinical means of identifying patients with the relevant biomarker-delineated subsets. Therefore, there is the need for comprehensive genomic testing, so no patient gets left behind.”
Additionally, there’s evidence that immune checkpoint inhibitor therapy, with drugs such as Keytruda (pembrolizumab) and Yervoy (ipilimumab), is ineffective in patients whose cancer is driven by certain genomic abnormalities, such as EGFR and ALK gene mutations. “Prior therapy with immune checkpoint inhibitors seems to significantly increase the danger of pneumonitis (inflammation of the lungs) — which can be debilitating, even life-threatening — when the correct targeted oral therapy agent is subsequently used,” Osarogiagbon says.
When it approves a targeted therapy, the FDA also often approves a companion test that can identify the biomarker for that targeted therapy. There are also tests developed by researchers and laboratories that haven’t been approved by the agency. “For companion diagnostic tests, the FDA has set the bar very high for accuracy and validation,” Quagliata says. “For assays that are not FDA approved, including LDTs (laboratory developed tests), Clinical Laboratory Improvement Amendments (CLIA) and the College of American Pathologists (there are) standards for high-complexity laboratories to safeguard the quality of tests.”
When it comes to the expense of testing, Quagliata says it is essential to pull back and the see the situation from a broader perspective. “Rather than put patients on inefficient therapies as a first-line treatment, genetic testing allows clinicians to make more informed decisions, becoming more efficient in their prescribing, thus helping save on downstream treatment costs,” Quagliata says.
Osarogiagbon says American healthcare is moving rapidly from tests for a single biomarker to comprehensive genomic testing because the broader approach is faster, safer and more cost-effective for patients. “Unfortunately, even though the cost of so-called next generation sequencing (NGS) is dropping as more testing options and vendors enter the market, there remains the perception that these tests are expensive and might not be paid for by third-party payers,” he says. Another major concern is the turnaround time. Getting an NGS result can take several weeks.
Insurance coverage of biomarker testing is a wild card into biomarker testing. “Reimbursement has become a complex matter as even within the non-small cell lung cancer space, differences exist in several areas that impact payer coverage, including sample type, test size, test content, use case, and the stage of disease,” Quagliata says. In general, among patients with late-stage NSCLC, Medicare provides coverage, Medicaid does not, and commercial plans vary, according to Quagliata.
But as more studies are done, Quagliata believes the evidence for NGS being more efficient and cost-effective will get stronger. Matching patients with targeted therapies at an earlier stage will reduce unnecessary spending for payers and patients.
Andrew Hertler, M.D., chief medical officer at New Century Health, a subsidiary of Evolent Health, says the cost of the biomarker testing ranges from $2,000 to $4,000, though there can be additional costs if there’s a need to re-biopsy the tumor. Hertler sees a challenge in making sure the tests are accurate. “There have been some very disturbing studies done where people have sent the same specimen out to multiple different laboratories and not had consistent results — I think somewhere on the order of 50% of the time — so we clearly still badly need to come up with standardized validated reliable procedures,” he says. But Hertler notes that variability may also be in the cancer itself. “We know cancers are genetically unstable.”
Avoiding ineffective treatments
The challenge in getting biomarker testing and targeted therapy is not so much with the patients as with their doctors and the healthcare systems in which they practice, as well as third-party coverage policies for these rapidly emerging options. Osarogiagbon is an adviser on the No One Missed campaign by LUNGevity Foundation, which brings essential education to the public around comprehensive biomarker testing in lung cancer.
“Patients quickly understand the benefit of this approach, given the striking improvements in results and greater convenience,” he says. “The main barriers are not patient-level; they are provider-, institutional- and social policy-level.”
Most clinicians are recommending comprehensive biomarker testing, which includes NGS and PDL1 Tumor Proportion Score testing.
“Single-gene tests waste time and expose patients to the danger of inordinate delay in identifying potentially lifesaving biomarkers that guide treatment,” Osarogiagbon says. “Ideally, these tests should be done reflexively when the patient diagnosed and the testing is automatically ordered, thereby saving precious time.”
Hertler says that when talking with patients, providers should explain biomarker testing methods clearly and note that targeted therapies don’t work for everybody, and even when they do work, the enthusiasm can have people carried away about the prospects. “People are doing better and have less side effects from their therapy and can live a more normal life, but we don’t have
Keith Loria is a freelance medical writer in the Washington, D.C., area.