Upfront PD-1 Inhibitor Monotherapy in Advanced NSCLC



Leora Horn, MD, MSc, FRCPC: Welcome to this OncLive® News Network presentation, broadcasting live from MJH Studios. Today’s discussion will be focused on the practical application of recent clinical data for immunotherapy in non—small cell lung cancer.

I am your host, Dr Leora Horn, Ingram Associate Professor of Cancer Research and clinical director of the Thoracic Oncology Program at Vanderbilt University Medical Center in Nashville, Tennessee.

Today I am joined by 2 colleagues who are also experts in lung cancer research: Dr Eddie Garon, associate professor of hematology-oncology at the UCLA [University of California, Los Angeles] David Geffen School of Medicine in Los Angeles, California; and Dr Thomas Stinchcombe, professor of medicine at the Duke Cancer Institute in Durham, North Carolina.

During the next 60 minutes we are going to navigate through some of the questions surrounding how we treat patients with non—small cell lung cancer. We’ll consider how we are currently using immuno-oncology agents, how they are sequenced with other therapies, and how the latest data will help us in making these decisions in our clinics. During the last few minutes of this broadcast we will answer questions that have been submitted throughout the program by members of our viewing audience.

Our first segment will focus on newly diagnosed non—small cell lung cancer. We’re going to discuss patients who have recently been diagnosed with metastatic disease.

The first trial to consider is KEYNOTE-042, a phase III trial comparing single-agent pembrolizumab with platinum-based chemotherapy in patients with advanced non—small cell lung cancer with a PD-L1 [programmed cell death ligand 1] score of greater than or equal to 1%. Eddie, how has this trial influenced how you’re treating your patients?

Edward B. Garon, MD: To date, it’s easy. The regimen has not been approved in patients with 1% to 49% PD-L1 expression, which is the group that is added to this from the KEYNOTE-024 study that did show a clear benefit in patients who have this high level of staining for PD-L1. That said, this study is not something that I find to be very easily applicable to my patient population. It was largely conducted in places where the ability to receive a PD-1 [programmed cell death 1] or PD-L1 inhibitor after progression is quite limited. In fact, only about 20% of patients did cross over to receive a PD-1 or PD-L1 inhibitor.

In addition, although there was a survival benefit, it was clearly driven mostly by patients who did have high-level staining for PD-L1—the group of patients for whom pembrolizumab is already approved as monotherapy. For the other patients who were a part of the study, for those with staining for PD-L1 between 1% and 49%, there was a hazard ratio of 0.92. Numerically, it looked a bit better for survival, but not tremendously better. Certainly, it didn’t look as good as the data that we have seen for chemoimmunotherapy combinations in that patient population.

The only group of patients I see this being of potential utility for is those who are at academic centers. Where we all practice, we tend to get a group of people who are looking to be aggressive in their care. In the real world, there are many patients who forego all treatment. There is the potential that this would take patients who might otherwise choose to forego treatment and have them consider undergoing single-agent PD-1 inhibition for the potential of a therapeutic response.

Leora Horn, MD, MSc, FRCPC: Tom, are you doing anything different? Do you have patients who come in with a PD-L1 score of 30% and absolutely refuse chemotherapy? Do you think this is something that could persuade them to consider some sort of therapy for their disease?

Thomas E. Stinchcombe, MD: I think there are a few patients, but we tend to select patients who want to be aggressive. We also have some patients who are maybe 85, 90 years old and have a PD-L1 score of less than 50%. These are the mutation-negative patients. I think you might, if this is approved, be able to offer that elderly patient an option when there are concerns regarding toxicity with the chemoimmunotherapy combinations. But, I think only a subset of our patients are really going to be influenced by this trial.

Transcript Edited for Clarity

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