Over the last decade and a half, there has been a rapid expansion of precision medicines, particularly impacting the care of patients with cancer. The development of therapies that specifically target alterations in a tumor’s genome has led to better outcomes for patients diagnosed with advanced cancers. Non-small cell lung cancer (NSCLC) has led the way in this space, with a number of approved therapies currently available in the U.S. that target known genomic alterations such as ALK, EGFR, and RET.
While the availability of these therapies can lead to improvements in treatment response, we know from data shared at ASCO in 2021, that about 50% of patients who are diagnosed with advanced NSCLC do not get their tumors fully and appropriately tested for genomic markers. This means that patients are missing the opportunity to try cutting-edge precision therapies early in treatment, or perhaps ever.
The promise of precision medicine, particularly in the metastatic NSCLC setting, is severely diminished by a lack of access to high quality and comprehensive diagnostic testing. Furthermore, the problem is not an absence of such tests, but rather operational and financial barriers which prevent patients from accessing these critical analyses.
A Closer Look into Comprehensive Testing
Let’s first start by level-setting on terminology. What do I mean when I say high-quality and comprehensive?
A high-quality test means one whose performance has been tested, reviewed and approved by experts in the field of molecular pathology and laboratory medicine. A comprehensive test, most simply, is one that can detect everything you need to know about your tumor in one test and with one sample (e.g., tissue or blood).
Oncologists and pathologists should work together to understand which diagnostic test is most appropriate for their patient. And patients can ensure that these conversations happen by asking whether the testing done on their tumor is covering all of the genomic changes and signatures relevant to NSCLC.
The good news is that precision oncology is well practiced in NSCLC, as compared to other cancer types and most comprehensive molecular tests include genomic alterations relevant to NSCLC. For NSCLC, there are 9 recommended biomarkers that oncologists and pathologists will test for. However, there is a strong case to be made for utilizing tests that look at even more genes (some look at 50 genes or even closer to 500), as there may be genomic biomarkers that become relevant as more targeted therapies enroll in clinical trials or get approved by the FDA.
Testing Involves a Complex Team and Coverage
Now that we understand the type of testing needed, why are ~50% of patients not getting tested before they receive their first treatment? The real answer is complicated and boils down to operational and financial barriers.
From an operational standpoint, molecular testing doesn’t happen in the same lab where the tumor is diagnosed as NSCLC. Instead, there is a complex dance between the interventional radiologist who gets the tumor tissue sample, the pathologist who makes the diagnosis slides, the oncologist who orders the test, the laboratory doing the testing and sending the results, and ultimately the oncologist and patient determining the right treatment plan based on the results. Often times these stakeholders are at different institutions and likely even in different states. These distances are not only physical but also technological – which is the reason many reports are still faxed physical copies from the labs to physicians! The one thing at the center of these complicated operational processes, and what keeps them unified is the patient with NSCLC. These operational barriers are real and can often be the reason patients don’t get the right test. But as a community of patients with NSCLC and care providers, we must build systems and processes to solve these problems and get our patients tested with the right test at the right time.
Secondly, while the cost of genomic testing has decreased tremendously in recent years, the price of testing remains high and out of pocket costs are a barrier for many. Insurance coverage of comprehensive testing is variable and often times based on arbitrary metrics that don’t reflect the comprehensiveness of tests only the number of biomarkers tested.
The Centers for Medicare and Medicaid Services’ (CMS) – the single largest payer for healthcare in the U.S. – National Coverage Determination (NCD) announced in 2018 it would cover comprehensive genomic profiling in metastatic cancers (including NSCLC) as long as certain criteria were met. This was a huge step, and the agency should be commended for this. However, many private payers have been slow to follow the example set by CMS and, even the CMS policy is overly restrictive. The reality is comprehensive diagnostics are not a true driver of cost in cancer care. And the use of a comprehensive and high-quality test at the time of diagnosis can actually save an oncologist from using an ineffective therapy. Patients, caregivers and advocacy organizations must continue to push payers to loosen restrictive coverage policies to allow broad and timely access to these diagnostics and their related therapies.
The Path Forward
As a molecular pathologist, an employee of an oncology company advancing precision medicines, and the son of a father who died too soon of cancer, I am in awe of the progress we have made as a field in oncology, thanks in part to targeted therapies. The technologies needed to match patients with targeted therapies exist. We as a group of physicians, patients and caregivers must demand that the financial and operational barriers don’t stand in the way of life-enhancing medicine.
Guest Author Bio:
Anthony “Nino” Sireci, M.D. vice president, clinical biomarker and diagnostics development, Loxo Oncology at Lilly. Dr. Sireci is a board-certified Clinical Pathologist and a practicing molecular pathologist. Prior to joining Loxo, he was an Assistant Professor of Pathology and Cell Biology at Columbia University and a medical director in the Laboratory of Personalized Genomic Medicine at Columbia Medical Center. He is an active member of the Association for Molecular Pathology (AMP) where he serves on the organization’s strategy committee. He is also a member of the Pathology Coding Caucus in the College of American Pathologists (CAP) and the Molecular Pathology Advisory Group in the American Medical Association (AMA). Dr. Sireci received a B.A. in chemistry from New York University and an MD from the Johns Hopkins University School of Medicine. He completed his residency training in Clinical Pathology at the New York Presbyterian Hospital-Columbia University Medical Center where he also served as chief resident. During this residency he also received an MSc in biostatistics from the Mailman School of Public Health at Columbia.
More on biomarker testing: You might also be interested in this article about finding the right time to ask about biomarker testing. Increasingly, cancer care is being approached with precision medicine methods that can offer personalized medical care based on a person’s genes or specific disease. View current RET lung cancer clinical trials.
