Liquid Biopsies Making Impact in Lung Cancer, Other Tumor Types

Anita T. Shaffer @Shaffer1
Published: Sunday, Feb 05, 2017
Mark R. Bowling, MD

Mark R. Bowling, MD

The noninvasive testing that has long been the goal of solid tumor analysis is making its presence felt in lung cancer, and other malignancies likely will not be far behind, experts say. Although many potential uses for liquid biopsies are envisioned, much work remains to be done to establish the clinical utility of these tests.

At the Vidant Health System in North Carolina, patients with advanced lung cancer who are candidates for molecular analysis will receive plasma-based testing at the same time that they undergo a traditional biopsy. Reports from the “liquid biopsy” are available within 3 to 4 business days, and specialists are finding that the ability to obtain speedy results is making an impact on treatment decisions and possibly on outcomes.

“If it’s adenocarcinoma, knowing that there might be certain markers that can make a difference for that patient’s treatment upfront and quickly is very helpful,” says Mark R. Bowling, MD, the pulmonologist who performs many of the biopsies conducted at the center. “You can do the same thing on tissue, of course, but you usually have to wait 14 days.

“As much information as you can have on a patient to help you make decisions as soon as you can is very important,” he added. “To the patient, it’s an emergency. You’re not going to fix it just by biopsying it—you have to start therapy.”

The use of liquid biopsy testing at the center, which serves communities with a population of 1.2 million people, illustrates the rollout of a noninvasive approach that has long been the holy grail of solid tumor analysis. The era of the liquid biopsy has arrived in clinical practice in the United States—at least in lung cancer—with an expanding toolkit from commercial and academic providers and a growing body of clinical evidence.

The Cleveland Clinic has named the liquid biopsy, a term broadly used to describe blood-based testing for genetic mutations, as one of the top 10 medical innovations poised to make an impact on patient care in 2017.1 As part of the Cancer Moonshot initiative, biopharmaceutical companies and academic institutions have agreed to collaborate on building a Blood Pro ling Atlas that will aggregate raw datasets from liquid biopsy studies along with relevant clinical data2.

Many exciting uses for liquid biopsies that span the spectrum of cancer diagnosis and care that leverage existing and emerging platforms are under study, yet the clinical utility of such assays is an evolving question.

The liquid biopsy “is here today and it’s already established, but the uses of it are much more limited than people understand,” said Nathan A. Pennell, MD, PhD, director of the Lung Cancer Medical Oncology Program at the Cleveland Clinic’s Taussig Cancer Center. “The validated uses are much more narrow. That may expand dependent on our identifying clinically proven uses for it as opposed to doing it because we can. There aren’t that many cases where being able to detect something in the blood has been validated to impact patient outcomes and survival. That’s what’s missing from a lot of the liquid biopsies.”

Pennell said 2 areas where the utility of liquid biopsies has been established thus far are in monitoring treatment for emerging resistance and in identifying targetable genetic mutations or fusions to guide therapy.

As a noninvasive diagnostic, the ability to learn such information from a blood sample is particularly helpful for patients who cannot undergo a biopsy or whose tumor sample is exhausted, noted Pasi A. Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute. Jänne co-chaired a workshop on liquid biopsies that the American Association for Cancer Research (AACR) and the FDA sponsored in July 2016.

“Today we have technology that can look at both single genetic alterations from cell-free DNA from the plasma or can sequence cell-free DNA from the plasma and look at multiple genetic alterations,” said Jänne. “Both academic institutions and commercial vendors are providing that. The vast majority of what we need today are predictive markers. We need to be able to guide the care of patients who have advanced cancer.”

Jänne said there is a pressing need for studies that compare the utility of liquid biopsies with tumor biopsies. “That is the body of evidence that we need for more drugs,” he said. “There are some clinical trials that are allowing entry based on blood-based genotyping, not necessarily tumor-based genotyping. One of the questions is whether that is as good. That remains to be determined.”

In the immediate future, Jänne expects liquid biopsies to be most beneficial in solid tumor types where targeted therapies already have been identified, starting with non–small cell lung cancer (NSCLC) and including colon cancer, breast cancer, and melanoma.


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