By: Anthony Sireci, M.D., senior vice president, clinical biomarkers and diagnostics development, Loxo@Lilly

Over the last fifteen years, the introduction of precision medicine has generated renewed hope for cancer treatment. We know that targeting actionable alterations in cancer patients may lead to clinical benefit. The emerging practice of personalized medicine has moved cancer care from a “one-size-fits-all” approach to a more individualized experience. 

The Value of Comprehensive Genomic Profiling in Cancer Care 

With the increase in the number of available targeted therapies in cancer, a full understanding of the genomic drivers of a person’s specific cancer is more important than ever before. Comprehensive genomic profiling (CGP) plays an essential role in ensuring patients get matched to the right treatment at the right time, based on their biomarker status. CGP includes the use of next-generation sequencing (NGS) technologies, which can look at multiple genes simultaneously in a tumor sample to potentially provide a more accurate diagnosis and treatment guidance compared to a single gene test approach, which is less efficient, particularly in lung cancer. Although the beginning of a cancer diagnosis can feel overwhelming, it is often the most important time to discuss biomarker testing with a patient’s care team. 

The National Comprehensive Cancer Network (NCCN) recommends a list of genomic alterations to test for in eligible patients with advanced or metastatic non-small cell lung cancer and CGP is one way to test all of these alterations in a single tissue sample. However, despite this guidance, CGP still remains underutilized and there is still work to be done to ensure increased access to treatment. 

So, what is needed to help make broad based molecular testing of all eligible lung cancers, preferably by a CGP method, the standard of care that it should be? 

A Path Forward to Broad Based Molecular Testing as the Standard of Care

Genomic testing following a lung cancer diagnosis should be customary – especially for people living with non-small cell lung cancer (NSCLC). More than 50% of patients with NSCLC will have an actionable genomic target within their tumors that may be targeted by FDA-approved treatments. However, due to underutilization, some patients are missing the opportunity to receive precision therapies early during their treatment – or perhaps ever. It is important to acknowledge existing barriers to testing that can limit a patient’s access to precision oncology treatments.

The process to adapt broad molecular testing platforms like CGP as a standard of care must be collaborative. Together, we need to work closely with a diverse set of healthcare partners such as health system stakeholders, diagnostic companies, doctors, patients, and advocacy leaders to push for efficient use of CGP. 

We must continue to push payers to loosen restrictive coverage policies and widen insurance coverage of molecular tests like CGP to increase access to treatment. Discussions should include the clinical and economic significance for CGP and the impact on the healthcare system. We need to collaborate closely with regulators to make sure high-quality testing is available while ensuring the oversight does not burden patients and providers and restrict access. 

Working to make testing easy-to-use may encourage more practitioners to order molecular testing like CGP and encourage patients to ask for it. By partnering with assay developers and in vitro diagnostic (IVD) manufacturers to help standardize these technologies, we can make genomic testing “less sexy” and more likely to be standard use at the point of histologic diagnosis. 

We must focus education on the impact of early CGP and the value of closing clinical practice gaps. Patients and healthcare professionals (HCPs) should feel equipped with powerful tools and resources to make informed treatment decisions. We must continue to underscore the weight of data-driven treatment decisions and early testing. We should urge HCPs to adopt CGP in accordance with clinical guidelines that push for making this routine care. 

In the Meantime, Advocate for Yourself

Precision medicine is still a rapidly evolving space. Now more than ever, patients are encouraged to take an active role in their treatment decision making. It’s critical that patients understand that the information from broad molecular testing like CGP can be empowering. A patient’s role during early decision making is key. We must continue to support patients so that they feel prepared to ask the right questions at the right time to inform their treatment journey.

View more blog posts by Nino.

Guest Author Bio:

By: Anthony Sireci, M.D., senior vice president, clinical biomarkers and diagnostics development, Loxo@Lilly

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. Biomarker testing helps to make an accurate cancer diagnosis and allows for treatments based on a person’s tumor.¹ For patients living with lung cancer, the advancement in targeted therapies has led to an increase in overall survival over the past ten years.²

Despite progress through the years to improve patient access to testing, we still don’t live in a world where all patients with advanced cancers receive high-quality and broad-based genomic profiling. As we move towards a new standard of care, it is critical for patients to understand the importance of biomarker testing and feel empowered and equipped with the right resources to know when to engage in discussions with their care team.

How to Advocate for the Right Testing at the Right Time

In order to receive a targeted therapy, a biomarker test is required to match the patient to the right treatment at the right time. The best way to know if a cancer has a treatable alteration is for patients to talk to their physician and treatment teams about how to get tested for all treatable biomarkers. And, depending on how advanced the cancer is, that might mean at diagnosis. Patients should feel empowered to be active participants in their diagnostic journey and treatment planning. One major way patients can become active participants in their treatment journey is by asking questions at key moments during the diagnostic and treatment selection journey.

Initial conversations about biomarker testing can be started with doctors at the time of tissue biopsy for diagnosis of cancer. Oftentimes, these biopsies are performed by interventional radiologists or pulmonologists, depending on where the patient is treated. Patients should ask about the amount of tissue taken during the diagnostic stage and ensure that it is not only enough for diagnosis of the cancer, but also to send additional molecular testing of the tumor. It’s important to ask this of the doctor ordering the biopsy, even before they initiate a biopsy so that a clear plan is in place. The need to rebiopsy if enough tissue isn’t initially collected is not only time-consuming but potentially dangerous. In addition to planning the appropriate amount of tissue, patients might also ask their care team about the plan for testing: which labs will be used and is the testing comprehensive of all the biomarkers an oncologist would need for making treatment decisions.

When collecting a biopsy, a proceduralist will remove cells or tissue from a given tumor and a pathologist will then examine the appearance of the cells and tissue to help determine a diagnosis. The pathologist will also send the tissue to a special lab for comprehensive molecular testing and that result can take up to two weeks to be received by an oncologist.³ Given this process, collecting enough tissue at the diagnostic stage can hopefully provide data available at the time of the first or next visit with an oncologist.

Even if enough tissue is collected at the time of procedure, turnaround times for genomic testing are high and samples can fail due to insufficient tumor tissue or low-quality tissue. It is worth talking to a proceduralist or oncologist about using genomic testing based on cancer genes circulating in the blood, or liquid biopsy/ctDNA. Ordering both tissue and ctDNA testing at the same time can expedite the receipt of results to the oncologist and mitigate the risk of sample failure down the line. A big risk for patients here is insurance coverage and should also be discussed.

Below are potential questions that patients can utilize when speaking with their interventionalist, or to remind their oncologist later on, in order to advocate for the best treatment options:

• Am I eligible for a biomarker test? If so, how would the test inform my treatment plan?
•  I’ve heard about comprehensive testing at labs that offer genomic profiling tests—Is this one test going to tell me all of the relevant results I need to know about biomarkers?
• Will my insurance cover a comprehensive biomarker test?
• I’ve heard tumor testing is the gold standard, but that it can take a long time. Can we discuss sending a liquid biopsy at the same time as the tumor sample?

It’s fundamental for patients to be given the right tools to understand how their biomarker results can impact their treatment journey. And patients can help ensure this by asking questions about their lab results, including what the biomarkers indicate in relation to their cancer diagnosis and treatment options. And it’s important that patients and doctors have these conversations at the right time.

Biomarker Testing is Worth the Wait

Although it may take several weeks to receive the results of a comprehensive biomarker test, waiting for the results before starting therapy is an important factor for which patients should advocate, if clinically possible. According to a recent survey, biomarker testing helped doctors tailor therapy for nearly 93% of respondent patients whose cancers were tested over the past three years.⁴

Biomarker testing ensures that a patient gets matched to an effective treatment for their cancer at the right time, making comprehensive biomarker testing “worth the wait” and worth the effort to advocate for proper testing when determining one’s treatment path.

Guest Author Bio:

More on biomarker testing: You might also be interested in this article about the importance of biomarker testing when facing RET-altered cancers. Over the last decade and a half, there has been a rapid expansion of precision medicines, particularly impacting the care of lung cancer patients and improving cancer treatment. Understanding the role of biomarker testing in identifying specific cancer cells and analyzing tumor tissue is crucial. View current RET lung cancer clinical trials to explore ongoing research and advancements in tumor testing for cancer treatment.

Newly diagnosed with RET-positive cancer? You might also be interested in Steps to take after a RET-positive lung cancer diagnosis.

Guest Author Bio:

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.