Biomarker testing drives lung cancer treatment

When determining treatment decisions for non-small cell lung cancer, biomarker testing—and particularly next-generation sequencing—offers essential information to guide therapy. “Next-generation sequencing is precision medicine at its best. It’s really important for choosing the correct treatment, and for avoiding treatments that might not be effective,” says Melina Marmarelis, MD, Assistant Professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania.

There is much work to do, however, to improve biomarker testing and ensure that all patients are receiving the tests that can inform their treatment. Dr. Marmarelis joined the Penn Medicine Physician Interviews podcast to discuss the current state of next-generation sequencing, and where the technology is headed.

Biomarker testing: Identifying targets before starting treatment

In the last decade, there has been a dramatic increase in the detection of biomarker targets and the development of targeted therapies. Those advances go hand in hand. While standard chemotherapy and immunotherapy treatments are unlikely to work in non-small cell lung cancer with EGFR gene mutations or an ALK gene fusion, for example, targeted therapy can be very effective. “Immunotherapy by itself isn’t effective for patients with EGFR or ALK alternations. If those alterations are detected, it’s important that they receive targeted therapy instead,” Dr. Marmarelis says. “It has become critical to understand the characteristics of the tumor before we start treatment.”

Yet, depending on the demographics and geographic area, about a quarter of patients don’t receive the recommended testing before initiating therapy, Dr. Marmarelis says. Moreover, in a large retrospective study of patients with metastatic non-small cell lung cancer, she and her colleagues found that approximately 30 percent of patients with biomarker-positive disease who did undergo next-generation sequencing did not receive biomarker-driven targeted therapies as their first-line treatment. The results were published in JNCCN.

Developing liquid biopsies for non-small cell lung cancer

Research to improve biomarker testing could help close these gaps. Tissue testing remains the gold standard for next-generation sequencing. But sometimes there is not enough tissue collected from a biopsy, or other tests exhaust the tissue sample before sequencing can be done. To address those limitations, Penn Medicine researchers are among the experts developing the science of liquid biopsies.

A plasma-based test, liquid biopsy detects pieces of cell-free DNA in the blood. Research at Penn Medicine has shown that concurrent use of liquid and tissue testing can improve the rates of target detection. “With two shots on one goal, you can increase the chances of detecting a target by more than 30 percent,” Dr. Marmarelis says.

To move that finding into a real-world setting, Penn Medicine researchers led a clinical trial across the health system to implement concurrent testing with liquid and tissue biopsy. “Since we know that detecting and delivering a targeted therapy has a survival advantage, operationalizing this is really important,” Dr. Marmarelis adds.

The future of next-generation sequencing

Liquid biopsy is particularly helpful to speed sequencing results in metastatic non-small cell lung cancer. “But in early-stage lung cancer, you often don’t have shedding into the blood. In those settings, we’re reliant on tissue testing,” Dr. Marmarelis says.

That’s changing, however, as researchers develop new, more sensitive approaches to liquid biopsy. One example is tumor-informed tests, which look first at the patient’s tumor and aim to detect similar markers in the blood. “Because they are so specific to the patient, they can detect things with much higher sensitivity,” Dr. Marmarelis says.

Penn Medicine researchers are also developing new ways to speed biomarker detection. One of the biggest challenges for tissue testing is that the results can take two to three weeks. “Patients don’t want to wait that long to make a decision about whether to start chemo-immunotherapy or go straight to surgery, so we’ve implemented a faster, more limited assay that has a turnaround time of about five days,” Dr. Marmarelis says. “That can get us the information we need to make initial decisions about perioperative therapy.”

As the science of sequencing continues to progress, Penn Medicine is reimagining its Lung Cancer Translational Center of Excellence—Thoracic Oncology Precision Program to accelerate advances in sequencing. When it began about a decade ago, the Center was focused on immunotherapy, which was then new in the lung cancer field. Now, the program has multiple projects centered around liquid biopsy in early-stage and metastatic lung cancer.

“We’re trying to figure out how to use these new tools to make better treatment decisions and give patients better outcomes,” Dr. Marmarelis says.

Referrals and consultations

Melina Elpi Marmarelis, MD, sees patients at the Penn Medicine Abramson Cancer Center. For a provider-to-provider consultation with Dr. Marmarelis, call 877-937-7366, or refer a patient online.