Updates in Immunotherapy for Advanced Thoracic Malignancies - Episode 6

Treatment for PD-L1 High/Low/Negative Non–Small Cell Lung Cancer

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Suresh Ramalingam, MD: How do you manage a given patient in your clinic? These don’t have to be long answers, just a quick choice of what would you do for a patient, let’s say a 70-year-old male with stage IV nonsquamous lung cancer, who has a good performance status. We talk about 3 scenarios: a patient with PD-L1 expression greater than 50%, 1% to 50%, less than 50%. Let’s talk about what’s your treatment of choice for that particular patient. Steve, greater than 50% PD-L1 expression, frontline treatment, what would you select?

Stephen Liu, MD: My standard right now is PEMBRO [pembrolizumab] monotherapy, and I use the every-6-weeks regimen. There’s some advantage to having patients come in less frequently. I personally have had good outcomes with it. My standard is pembrolizumab monotherapy for PD-L1 high. For PD-L1 low, it’s pembrolizumab/chemotherapy for me. The chemotherapy/IO [immunotherapy] combinations provide a benefit across PD-L1 strata. I like the combinations for the low. And for PD-L1 negative, even though off label, I am using more NIVO/IPI [nivolumab and ipilimumab] in that setting. Really good outcomes there in that PD-L1 negative. The duration of response is compelling there. The outcomes again across subsets, a little better for the PD-L1 negative and the PD-L1 low. I don’t have a great reason as to why, but that would be my standard today. It might change tomorrow.

Suresh Ramalingam, MD: Fair enough. Christine?

Christine Bestvina, MD: For PD-L1 high patients, I start with pembrolizumab monotherapy, with a short interval CT scan at 6 weeks to make sure we’re headed in the right direction. For PD-L1 expression of 1% to 49%, I do use combination carboplatin, pemetrexed, and pembrolizumab, and then for PD-L 0%, it’s either triplet combination chemotherapy/IO versus ipilimumab/nivolumab based off of patient characteristics and also patient preference.

Suresh Ramalingam, MD: Great. Thank you. Martin?

Martin Dietrich, MD, PhD: I would add a clinical selection, we didn’t get into this with CheckMate-227, but a patient selection based on the symptomatology and tumor volume is a major factor for the up-front well-being of a patient. Six weeks may be a little bit earlier than what I would scan. But we’re all in agreement that the first 3 months decide the fate of a patient with immunotherapy. If I have a feeling that somebody were to deteriorate early, I would always add chemotherapy, independent of PD-L1 level. They need 6 to 12 weeks in my opinion, to give immunotherapy a fair shot. If I have somebody who has high PD-L1, meaning greater than 50%, and low symptomatology, I think PD-L1 plus ipilimumab or PD-L1 alone are reasonable options. If I have PD-L1 low versions, from 1% to 49%, that’s chemoimmunotherapy or ipilimumab/nivolumab, depending on preference. The same is true for the PD-L1 negatives. They stand square side by side in terms of what we want to look at. But what this discussion highlights is that with all these different concept options, that we need a trial that really compares these side by side, so that we know how they individually work out in their respective fields of study. The studies are close enough to draw some conclusions, but not to have a strong comparison, which is why our regimens all look a little bit different and they’re probably all on the reasonable side.

Firas Badin, MD: It’s easier to say what we don’t use than what we use because we have a lot of options. I can tell you, I rarely use chemotherapy in strongly positive PD-L1. Most of us, unlike my colleagues, I will either do pembrolizumab alone or nivolumab/ipilimumab in strongly positive PD-L1. In PD-L1 negative, I tend to do combination, either IO-IO, nivolumab/ipilimumab, or chemotherapy plus IO. And then 1% to 49%, again the same thing, it depends on the patient. It depends, like Martin mentioned, symptomatology and how fast you would like to get a response. But I’m moving away from chemotherapy, and I’m using more immunotherapy, either pembrolizumab alone or nivolumab/ipilimumab now.

Suresh Ramalingam, MD: Great. This nicely summarizes where we stand in terms of frontline treatment of non–small cell lung cancer for patients who don’t have a driver mutation. I want to thank our panel for discussing all the exciting new abstracts.

Transcript Edited for Clarity