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Phillip Febbo on Recommendations for Equitable Implementation of Liquid Biopsy

– 'Call to action' for ovarian and other cancer patients to have access to ctDNA-detecting tests


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Liquid biopsies -- tests that detect circulating tumor DNA (ctDNA) in the bloodstream -- have the potential to transform cancer by reducing health inequities in screening, diagnostics, and monitoring, researchers said in a review in . There are still significant challenges, however, that limit the accessibility.

The tool is already used to enable detection, interception, and more efficient treatment of cancer, and will become increasingly available over the next decade, Lauren Leiman, MBA, executive director of BloodPAC (Blood Profiling Atlas in Cancer), and colleagues predicted. BloodPAC is a consortium that aims to create an open database for liquid biopsies to accelerate safe and effective blood profiling diagnostic technologies.

In the following interview, study co-author Phillip Febbo MD, chief scientific officer and chief medical officer of Veracyte, a cancer diagnostics company based in South San Francisco, reviews the barriers to access liquid biopsy and recommends ways to enhance equitable access for ovarian and other cancer patients.

What does the study add to the literature?

Febbo: Liquid biopsy is becoming more a part of cancer care. We present a call to action for every patient to benefit from liquid biopsy and to diminish potential disparities. We also take a thoughtful look at challenges as new technology enters into medicine.

In ovarian cancer, liquid biopsy offers great promise in screening. To date, there is no effective screening for ovarian cancer. It's quite clear that cell-free DNA offers a way to find an early signal in ovarian cancer.

In early work, the Grail multicancer early detection blood test shows 83% sensitivity for ovarian cancer. As we see tests like this come into the market, this will be the biggest way to shift towards better early diagnosis. Once studies demonstrate good performance and utility, we want to make sure everyone has access.

Blood-based tests are becoming available for cancer screening, treatment, and monitoring. This is important for ovarian cancer. American Cancer Society statistics show improved ovarian cancer survival for white women from 45% in 1975 to 50% in 2013, but survival has remained unchanged at 42% among Black women. When there's technology to improve care, there has to be a path to ensure that everyone benefits.

What is the promise of liquid biopsy in general?

Febbo: Liquid biopsy will fundamentally change how cancer patients are managed and will improve outcomes. It's already known in settings of cancer screening, but as we come up with blood-based screening, we expect better compliance and earlier diagnoses.

There are currently approved by the FDA for clinical use to inform eligibility for more than 17 different therapies in ovarian cancer, breast cancer, non–small-cell lung cancer, prostate cancer, and colorectal cancer, as well as one companion diagnostic for all solid tumors. Liquid biopsies are rapidly becoming embedded into treatment decision-making, especially given the faster turnaround time compared with tissue testing.

There is a particular need for ovarian cancer, pancreatic cancer, and glioblastoma, which are all very challenging diseases. Ovarian cancer patients shed ctDNA early on. We need to know how to detect this signal and move care forward. Many ovarian tumors have BRCA1 and BRCA2 genes inactivated, and are sensitive to PARP inhibitors. If we identify the disease earlier and add PARP inhibitors into platinum therapy, we may cure more ovarian cancers. After ovarian cancer surgery, cell-free DNA may help identify any remaining disease.

What are some of the barriers to clinical adoption and patient access to liquid biopsy?

Febbo: In many communities when a new technology is introduced, some are excited, some are not. This may have to do with a lack of familiarity or trust in the healthcare system, and incomprehensible medical jargon. Others may be skeptical that a new technology will work on patients like them.

What's needed to break through these barriers?

Febbo: We need to incorporate communities into the discovery, development, and implementation of new technologies. Appropriate studies can demonstrate performance in all groups. Insurance coverage policies should cover new tests and should not be too expensive. To generate more confidence, we need patient-friendly, plain-language literature and educational materials.

Veracyte has developed a noninvasive test designed to improve lung cancer risk assessment so that physicians better know what to do next after a lung nodule has been found. A clinical utility study to assess the impact of the test's use on patient care is currently underway, and 16% of the patient population enrolled to date are African American, which reflects the U.S. population. We are proactively opening up more sites in Southern California to enroll more Hispanic patients.

What are the potential clinical applications of liquid biopsy for ovarian cancer in terms of monitoring treatment response, detecting recurrence, and determining prognosis?

Febbo: By detecting minimal residual disease, cell-free DNA can show whether a patient is responding to therapy. Once a tumor is removed, cell-free DNA should disappear within a few days. Clinicians can also use cell-free DNA a month later to check for a meaningful response. If the clinician detects a signal of cell-free DNA after therapy, then prognosis is not good.

What is your main message to practicing oncologists?

Febbo: Liquid biopsy will fundamentally change how oncologists can access and evaluate cancer patients, including women with ovarian cancer. We need clinical trials to generate more data. Blood samples can and will help in monitoring and treatment of patients.

Read the review here.

Febbo reported employment/leadership at the time of the study with Illumina and Varian; other co-authors, including Leiman, reported various relationships with industry.

Primary Source

JCO Precision Oncology

Source Reference:

ASCO Publications Corner

ASCO Publications Corner