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Biomarkers for Frontline Immunotherapy Pose Obstacles in NSCLC

Caroline Seymour
Published: Tuesday, Jul 24, 2018

John A. Kosteva, MD

John A. Kosteva, MD

Although PD-L1 has been coined an “imperfect biomarker” and tumor mutational burden (TMB) is still investigational in many ways, the adoption of immunotherapy agents into frontline treatment continues for patients with non–small cell lung cancer (NSCLC), despite the inability to accurately select patients, said John A. Kosteva, MD.

“We’re still trying to tease out which patients might be best for combination immunotherapy, single-agent immunotherapy, and chemotherapy plus immunotherapy,” he explained. “Whether we use TMB, PD-L1, or comorbidities, we still have some work to do to sort that out over the next couple months to years.”

Until these assays are further refined, Kosteva said that the decision to use immunotherapy often lies in a physician’s ability to discern a patient’s disease burden and symptomatic disease from more indolent NSCLC.

In an interview during the 2018 OncLive® State of the Science Summit™ on Non–Small Cell Lung Cancer, Kosteva, clinical assistant professor of medicine, University of Pennsylvania School of Medicine, Abramson Cancer Center, discussed the adoption of immunotherapy into the treatment paradigm for patients with NSCLC.

OncLive: What are the criteria that qualify a patient for immunotherapy?

Kosteva: When we meet patients for the rst time and do their initial staging, we are always adding molecular and PD-L1 studies to help us sort out the best treatment options. With any immunotherapy drug, we’re always looking for any contraindications. A patient who had an organ transplant might be at risk for rejection or a patient with poorly controlled autoimmune disorders on high-dose steroids might sway us one way or another. Based on some of the recent studies from the 2018 AACR Annual Meeting and the 2018 ASCO Annual Meeting, we’re pushing immunotherapy drugs to the frontline setting for most patients across the board with lung cancer.

Are physicians relying less on PD-L1 and more on TMB these days?

We’re going to be looking more at some of the immunotherapy combinations with TMB. Right now, it’s not quite ready for prime time in the community yet. It is a pretty specific test, but a lot of different genetic testing companies are looking at how it can help clinicians sort out TMB. It’s certainly something we are working on in our health system to see how we can measure [TMB] and make this part of routine testing.

How do you determine whether to give single-agent or combination immunotherapy?

Right now, PD-L1 is still the best test we have to help sort that out. Patients with 50% or higher PD-L1 expression might be eligible for single-agent pembrolizumab (Keytruda). It’s still a case-by-case basis. It’s a whole new world that we weren’t used to a couple months ago. We are still trying to sort out the patients who will be the most likely to benefit from single-agent immunotherapy versus chemotherapy/immunotherapy or immunotherapy/immunotherapy.

If a patient has PD-L1 expression greater than 50% and is eligible for frontline single-agent pembrolizumab, I look at their disease burden to see how symptomatic they are. [I have to determine] if this is a patient who needs to get their disease under control quickly with a rapid response. Patients with fairly symptomatic disease and high TMB are the patients you want to put a priority on getting a high response rate with frontline treatment. These are the patients you’re concerned might not have a good shot with second-line therapy. Therefore, you want to try to go “all in” now because your first-line of treatment is going to be your best and only chance to get their disease under control. These are the patients I would give triplet therapy with pembrolizumab and standard chemotherapy to.


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Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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