Biomarker Testing Is Not Keeping Up With Drug Innovations

Despite the tremendous progress made over the past decade in developing targeted oncolytic therapies, testing for specific mutations — or biomarkers — to determine the proper candidates for those treatments lags behind. A few states have passed or are considering legislation requiring insurers to cover biomarker testing, with California becoming the most recent state to pass such a law.

Non-small cell lung cancer (NSCLC) is one area that has undergone the most development. There are now more than two dozen drugs that target nine different changes in NSCLC cells that help them grow. But an article published July 7 in Cancer Therapy Advisor — which summarized a presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting — revealed that less than half of people with metastatic NSCLC received a test for five analyzed biomarkers before starting first-line treatment.

In October, California Governor Gavin Newsom (D) signed into law legislation that prohibits health insurers that cover biomarker testing from requiring prior authorization for people with advanced or metastatic stage 3 or 4 cancer. SB 535 defines “biomarker test” as a “diagnostic test, such as single or multigene, of the cancer patient’s biospecimen, such as tissue, blood, or other bodily fluids, for DNA or RNA alterations, including phenotypic characteristics of a malignancy, to identify an individual with a subtype of cancer, in order to guide patient treatment.” The law applies to health care service plan contracts “issued, amended, delivered, or renewed on or after July 1, 2022.” Also included are contracts, including Medi-Cal managed care plan contracts, with the State Department of Health Care Services.

AIS Health, a division of MMIT, recently spoke with Wendy Levin, M.D., M.S., chief medical officer at Biofidelity, a company whose ASPYRE technology provides ultra-sensitive, comprehensive biomarker results quickly, about SB 535 and molecular testing overall.

AIS Health: Could you please comment on the passage of SB 535 and why it’s so important?

Levin: The new California law, as well as similar ones that other states have passed or are currently considering, aims to increase timely access to genomic testing for late-stage cancer patients. Specifically, SB 535 prohibits health care insurers that already cover biomarker testing from requiring prior authorization for patients with advanced cancer.

This is important because it will increase the number of patients who may be able to access targeted cancer therapies, which have shown improved outcomes and better tolerability across cancer types as compared to one-size-fits-all treatments like chemotherapy. The selection of these targeted therapies depends on patients having access to comprehensive biomarker testing, so anything that removes barriers or reduces delays in testing is an important step forward in advancing the use of precision cancer treatments.

But while this new law is certainly a step in the right direction, some say it doesn’t go far enough, as it only applies to payers that already cover biomarker testing and is limited to late-stage disease. There is still a lot of work to be done to identify and address all obstacles that prevent widespread access to genomic testing, such as requiring coverage from all health insurers and expanding coverage to include early-stage patients. Only then can we ensure that all patients diagnosed with cancer have access to the very best treatment options.

AIS Health: What are the reasons why people are not receiving molecular testing? How can these be addressed?

Levin: Despite evidence of the clinical benefits of precision medicine, molecular testing rates lag behind clinical guidelines and advancements in the field. A study of genomic testing trends in the community oncology setting found that less than 60% of eligible NSCLC patients were tested for EGFR mutations — and this was several years after such testing became the recommended standard of care by the National Comprehensive Cancer Network (NCCN).

Researchers identified several barriers to molecular testing, including coordination of sample handling, long turnaround times, unclear test reimbursement, lack of access to targeted therapies, insufficient tissue and patient harm from repeat biopsies if the tissue sample is insufficient.

Unfortunately, these challenges are not unique to lung cancer or the community oncology setting. In fact, less than half of metastatic cancer patients in the U.S. who could benefit from targeted therapy are actually undergoing this molecular testing that can guide their treatment and improve outcomes.

One of the biggest barriers to widespread adoption of biomarker testing is the significant gap that exists with current testing options in terms of the ability to provide genomic data quickly, comprehensively and in a cost-effective manner. At one end, there is real-time PCR, a fast and inexpensive technology that is readily available in most laboratories worldwide. But at most, PCR can only test small numbers of mutations across a few genes at a time, making it far too limited for current treatment recommendations where there are often multiple actionable driver genes and mutations.

On the other hand, next-generation sequencing (NGS) provides a wealth of genomic information across hundreds of genes, but a majority of that information isn’t clinically actionable. The complexity of NGS tests has also resulted in the centralization of testing in a small number of specialist laboratories, contributing to slow turnaround times. This, combined with the high costs of NGS testing, has led to poor accessibility for most patients.

Complicated results with extensive reports can make interpretation of NGS tests challenging, as well as complicate integration with electronic medical records, particularly in the community cancer center setting. While far more comprehensive than PCR, NGS is too complex, slow and expensive to enable most patients to access the benefits of precision therapies and receive the optimal treatment for their disease.

A technology that quickly provides comprehensive yet clinically actionable information for hundreds of dollars or less, and is simple enough to enable broad adoption in smaller hospital laboratories, would break down the remaining barriers that prevent many cancer patients from accessing biomarker testing.

The underlying principle behind Biofidelity’s ASPYRE technology is to address this key problem in cancer diagnostics: giving oncologists the ability to detect genomic alterations with extreme specificity and sensitivity in a way that can scale to large numbers of genes, while also maintaining the simplicity, speed, low cost and ease of adoption of PCR. This will ensure that every oncologist, from prestigious academic institutions to small community cancer centers, can utilize comprehensive biomarker testing to make rapid, precise treatment decisions for all cancer patients.

AIS Health: About how long of a time period is there between when a provider orders a test and when it’s actually conducted? How long does it take to get results?

Levin: Clinical turnaround time (TAT) is defined as the time from when a biopsy confirms a cancer diagnosis to when the patient starts treatment. Even for the few academic institutions that have in-house NGS capabilities, this can still take an average of four to five weeks, depending on the specific panels. Most NGS testing is centralized, meaning physicians have to send the tissue samples to a central lab, further increasing the clinical turnaround time.

A recent study of biomarker testing trends reported a turnaround time of six days from diagnosis to NGS test order and 28 days between the test order and receiving the results. While NGS turnaround times have decreased over the years, patients are still waiting on average five weeks from their diagnosis to begin their targeted treatment. When dealing with a devastating diagnosis like cancer, this is an unacceptably long wait that can have a significant impact on patient outcomes, as well as add enormous psychological stress for patients and their families.

Sometimes the cancer is so aggressive that waiting five weeks could be life-threatening, forcing doctors and patients to make the agonizing decision to start immediate chemotherapy prior to receiving biomarker data, despite the potential increased safety risks and marginal clinical benefits.

A survey of both academic and community-based oncologists confirms that treatment decisions are often impacted by delayed test results. While 98% of respondents believed they should receive biomarker results within one to two weeks of ordering, 37% waited an average of three to four weeks for results. Many respondents reported that they are more likely to initiate a non-targeted, systemic therapy if results are not available after two weeks.

Clearly, these prolonged turnaround times can be a major obstacle for starting patients on targeted therapies. The sooner the genomic data are available, the sooner patients can be treated with an informed treatment plan that has the potential to significantly improve outcomes.

AIS Health: What are the reasons why health plans do not cover these tests?

Levin: With the explosion in personalized medicine and genomic testing in the past 20 years, insurance companies are understandably interested in containing their costs. They want to be sure they’re identifying patients with specific cancer diagnoses that are most likely to benefit from these targeted therapies.

In many ways, the clinical gaps in the biomarker testing landscape are mirrored in the reimbursement challenges. Comprehensive NGS testing often provides enormous amounts of information, but the large majority is not clinically actionable, the costs are very high, and the turnaround times are generally weeks; as a result, both public and private insurers are reluctant to pay for these multi-gene non-actionable panels.

Payers are more likely to cover PCR-based actionable single-gene tests, which are faster, less expensive and more widely available than NGS testing. But as precision medicine advances to encompass more genes and mutation targets, PCR-based testing is not comprehensive enough to fully inform effective treatment selection, due to its lack of scalability and significant tissue requirements.

While laws like SB 535 are an important step forward, technological innovations could significantly help expand coverage for genomic testing by making it readily accessible, faster and less expensive while providing comprehensive yet clinically actionable results.

AIS Health: Are there any misperceptions about molecular testing that are hampering its use?

Levin: A recent study sheds some light on patient perspectives regarding molecular tumor profiling, which revealed both perceived benefits and drawbacks of undergoing testing. The most commonly cited benefits included: access to personalized therapies, contributing to research that could help others and identifying cancer risks for family members.

Commonly cited drawbacks and misconceptions included the burden of waiting for test results, the fear of coping with negative results/information, skepticism of the science and the potential for inconclusive or false results, as well as genetic guilt and the fear of bearing bad news to family members. While patients’ attitudes about genomic testing were overall favorable, it’s apparent that addressing misconceptions and educating patients about the test and its implications will help improve access to this important information.

AIS Health: What do payers, providers and patients need to know about molecular testing?

Levin: Molecular profiling is revolutionizing cancer care by helping to shift the focus from treating illness to maintaining health. The ultimate goal is that one day we can turn incurable cancers into chronic diseases that have little impact on patients’ day-to-day lives.

In the past 20 years, DNA sequencing has transformed our understanding of cancer. Knowledge of the genetic pathways that drive disease enabled the development of new therapies that directly target specific genetic mutations. The result is individualized cancer treatments that offer better outcomes for patients, with fewer side effects and an improved quality of life.

Despite our understanding of what information physicians need to treat patients most effectively, we still lack the technology to quickly and easily unlock that information. At Biofidelity, we have an opportunity to make an immediate impact on patients’ lives. Every patient should have access to biomarker testing that is fast, inexpensive and provides actionable results — and that’s what our technology will accomplish.

Contact Levin through Liz Dowling at

This story was reprinted from AIS Health’s monthly publication RADAR on Specialty Pharmacy.

© 2024 MMIT
Angela Maas

Angela Maas

Angela has an extensive background of editing, reporting and writing for trade and consumer publications. She has written Radar on Specialty Pharmacy since she joined AIS Health in 2005 and has broad knowledge of the various issues at play within the space. She also has written for Spotlight on Market Access since its 2017 launch. Before joining AIS Health, she was managing editor at Employee Benefit News and Employee Benefit News Canada and managing editor at Hem Aware (a hemophilia publication), Lupus Living and Momentum (a multiple sclerosis publication). She has a B.A. in English and an M.A. in British literature from Arizona State University.

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