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Expert Tackles Efficacy of PD-L1 Testing for NSCLC in 2017

Gina Columbus @ginacolumbusonc
Published: Tuesday, Mar 28, 2017

Daniel B. Costa, MD, PhD

Daniel B. Costa, MD, PhD

In 2017, a lung cancer diagnosis must be accompanied by biomarker testing, whether it be for a genomic alteration, such as EGFR, ALK, or ROS1, or the immune marker PD-L1, according to Daniel B. Costa, MD, PhD, MMSc.

Moreover, even with FDA-approved agents designed to target these abnormalities or expression levels, researchers are still hoping to uncover additional markers and match novel therapies to them.

“It needs to be enforced that, if you want to appropriately treat advanced NSCLC in 2017, testing needs to be done,” said Costa, an associate professor of medicine at Harvard Medical School, medical staff, Hematology/Oncology, medical director of the Cancer Clinical Trials Office, and Medical Center Thoracic Oncology Group Leader, of Beth Israel Deaconess Medical Center. “It is almost impossible to talk to a patient who doesn’t already understand that there is tumor heterogeneity and that every patient is treated differently. There is no cookie-cutter way to treat a patient anymore.”

In an interview during the 2017 OncLive® State of the Science Summit on Advanced Non–Small Cell Lung Cancer, Costa spoke on biomarker testing in NSCLC and the necessary next steps for PD-L1 testing in these patients.

OncLive: What are the immediate next steps with PD-L1 testing for patients with NSCLC?

Costa: If you treat advanced NSCLC now, we cannot think of the disease as a one-size-fits-all approach after diagnosis anymore. It really requires substratification, and we are going beyond just the histological differentiation between the most common types of NSCLC: squamous cell carcinoma and adenocarcinoma. We are going beyond that to genomic markers and biologic markers.

PD-L1 is a very important biomarker that has clinical implications. This protein is expressed both in tumor cells and in the microenvironment of the tumor. It’s been consistently shown now—depending on the way that you try to monitor this—to predict that if you use the correct assay, the greater benefit of drugs that unleash the immune system.

More specifically, pembrolizumab’s (Keytruda) approval is based on the expression of PD-L1, so we know that the higher the expression of PD-L1, the higher the rate of antitumor response and tumor control. Now that this drug is approved based on this biomarker, it is increasingly important that all patients with NSCLC test for it. 

What other promising biomarkers are we exploring?

If we are talking about immune-based therapies, PD-L1, in my particular view, is a very clinically useful biomarker because it can be done routinely in most of the samples that we have and it doesn’t have clinical implications. However, it’s not the perfect biomarker. The presence of PD-L1 expression, even at the highest level, doesn’t necessarily predict a 100% response rate. It is clear that there needs to be more refinements if we can really dwindle down on the patients who would or would not respond.

There are other biomarkers that are very important and will likely become part of an assessment of immune response. PD-L1 is just one of many, and others will come through for expression in both tumor cells and the tumor-infiltrating microenvironment.

The other one is the mutation burden of the tumor. It is obvious that a tumor is invading the immune system because something is happening as it’s becoming a tumor or becoming metastatic. This leads to differences within the tumor that would lead the immune system to attack, and that’s why the immune system wants to invade it.

The road of advanced genomics, to look at neoepitopes and tumor burden, will also be important. However, if you look at what is clinically indicated and can be translated to the clinic right now, we are somewhat stuck—at least in the immediate future with PD-L1 expression. However, it’s obvious we want to build on that either with other ancillary or other advanced tests that can supplement PD-L1 expression in the tumor. 

Are there ongoing trials in this space?

Yes. The whole community is very excited to see biomarker-driven trials. We are talking now about PD-L1, but there are also genomic markers being used routinely in the clinic such as EGFR mutations, ROS1 gene rearrangements, and ALK. We have drugs approved for them. The community is excited with the idea that you can subdivide cases and you can use these biomarkers to develop drugs or combinations of drugs.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Year in Review™: Reflecting on Recent Evidence With an Eye to the Future of Lung Cancer ManagementMar 30, 20191.5
Online Medical Crossfire®: 5th Annual Miami Lung Cancer ConferenceMay 30, 20196.5
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