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Levy Lends Insight on Immunotherapy Biomarkers in NSCLC

Caroline Seymour
Published: Saturday, Sep 08, 2018

Dr. Benjamin P. Levy
Benjamin P. Levy, MD
Established and emerging biomarkers are demonstrating predictive value with immunotherapy for patients with non–small cell lung cancer (NSCLC), but equally as compelling are those that can predict lack of response, said Benjamin P. Levy, MD.

Biomarkers of response to immunotherapy include PD-L1, tumor mutation burden (TMB), and potentially KRAS alongside TP53, whereas biomarkers that serve as deterrents include EGFR mutations and, most recently, LKB1 or SKT11 mutations.

“These are readily available mutations to interrogate on tumors that may soon help guide decision-making, if not now,” said Levy, adding that physicians must continue to search for better predictive biomarkers both in tissue-based and plasma-based assays.

In an interview during the 2018 OncLive® State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Levy, assistant professor of Oncology, clinical director, Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Sibley Memorial Hospital, discussed established and emerging biomarkers that could have predictive value with immunotherapy.

OncLive: What biomarkers should physicians be aware of?

Levy: We have come a long way. We know that PD-L1 remains a biomarker. The cutoff point of 50% is still used to drive decision-making. There are other biomarkers to consider, such as TMB. This is a story that is beginning to be told. I don't think the story is completely done yet. TMB may be another biomarker to look at that may predict efficacy to either single checkpoint inhibitors or dual checkpoint blockade, as we have seen from recent data published in the New England Journal of Medicine.

There are other emerging biomarkers that are consistently showing benefit or predictive value with immunotherapy. One of those is KRAS with TP53. This is a story that's starting to be told. Data were published in July 2018 looking at KRAS mutations and TP53 occurring alongside them. Data showed that if you have those 2 alterations together, there may be a higher likelihood of response to immunotherapy.

Those are important predictive markers for benefit, but just as important are markers that may predict lack of benefit to immunotherapy, [so we know] who not to use immunotherapy in. The ones that have emerged with data have been EGFR mutations, at least for single-agent checkpoint inhibitors. There have been consistent data that have suggested that EGFR-mutant NSCLCs do not respond to immunotherapy. Then, more recently, LKB1 or SKT11 mutations also may predict lack of benefit to immunotherapy.

Are PD-L1 and TMB routinely tested for at Johns Hopkins Medicine?

We're still working out TMB in-house. We are still waiting to get it validated, but PD-L1 is of course tested for. EGFR mutations are tested for, and KRAS is also looked at. We do a next-generation panel that gives you the co-alterations with KRAS, as well. LKB1, a marker that may demonstrate lack of benefit to immunotherapy, is also tested in our next-generation panel.

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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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