Treatment of Advanced NSCLC With Immune Checkpoint Inhibitors

John V. Heymach, MD, PhD: We’ll move over to immunotherapy treatment for those without oncogenic drivers primarily. One of the important advances in our field is we often can start patients now on chemotherapy-free regimens with just immunotherapy. There have been a number of studies showing that immunotherapy in the right patient population can be better than chemotherapy. Talking about a regimen that we’ve heard about before but is pretty widely used, Vamsi, do you want to just talk about pembrolizumab vs chemotherapy, the KEYNOTE-024 trial update?

Vamsidhar Velcheti, MD: Certainly. We’re all very familiar with this regimen and the data from KEYNOTE-024. The study that was recently published was a 5-year follow-up, which confirmed what we already know. Patients with PD-L1 TPS [tumor proportion score] greater than 50% do much better with pembrolizumab compared with chemotherapy. The 5-year survival rates with pembrolizumab in this particular population was 32% vs 16% with platinum doublet. No big surprises there. We knew that a population of patients could really benefit from PD-1 monotherapy like pembrolizumab in the high population. But PD-L1 is here to stay in terms of trying to select for those patients. The bigger question is who are those patients who would benefit just from PD-1 monotherapy? We’re not there yet. A lot of other co-alterations and novel biomarkers are being investigated, and that we’ll probably be able to select better.

John V. Heymach, MD, PhD: Hearing those numbers—one-third of patients surviving at 5 years—that’s pretty remarkable progress just by introducing immunotherapy. That’s quite an advance.

Ani, there’s a similar study with atezolizumab, the IMpower110 study. Do you want to briefly take us through this study and how it may be similar or different?

Ani Balmanoukian, MD: Yes. The design was similar in that it took patients with non–small cell lung cancer [NSCLC] and randomized them to either atezolizumab 1200 mg IV [intravenous] every 3 weeks vs chemotherapy, 4 to 6 cycles of platinum doublet chemotherapy in the other arm. What we saw was the same idea in that patients with high PD-L1 expression greater than or equal to 50% benefited vs chemotherapy, with a median overall survival of around 20 months with those on atezolizumab vs 13.1 months with chemotherapy. It’s the same idea where we see that those with high PD-L1 expression definitely do benefit from single-agent atezolizumab in the frontline setting.

John V. Heymach, MD, PhD: Right. Heather, 1 more drug into the mix is cemiplimab. It’s a drug we use a lot for cutaneous squamous cancers but didn’t have as much experience in lung cancer. Do you want to take us through the EMPOWER-Lung 1 study?

Heather Wakelee, MD: Sure. Cemiplimab is another PD-1 inhibitor, and there’s not a lot to distinguish it much from some of the other PD-1 inhibitors that we have. The drug development plan has been pretty similar to what we’ve seen before. The EMPOWER-Lung 1 study, which has now been published, was looking in patients across the board but focusing on the greater than 50% PD-L1 expression. When you look at the response and the duration of response, it’s hard to distinguish it from other similar agents. In the publication, we didn’t have the final overall survival compared with the standard arm. It looks good. There was more recently in combination with chemotherapy, but we’re going to talk about that in a bit.

John V. Heymach, MD, PhD: Stephen, you’ve got pembrolizumab, atezolizumab, and cemiplimab approved in PD-L1 greater than 50%. Any thoughts about important distinctions between them? How do we choose?

Stephen Liu, MD: They’re all more similar than different. They’re different drugs, but I’m not sure we’re in a position to leverage any of those differences. There are some nonclinical changes. Pembrolizumab can be given every 6, atezolizumab certainly can be given every 4. That may make a difference in some situations, but frankly, most of the difference—if I were to be influenced to use 1 over another—would be things like cost, access, formularies, insurance authorization, and personal comfort. It’s good to have multiple options, and hopefully we’ll move beyond them.

John V. Heymach, MD, PhD: I agree with that. Ultimately it will be the combinations that get built on top of these that are more likely to distinguish them from the drugs themselves. I guess it’s good to have both Coke and Pepsi to drink, but we’ve got to see what comes next. It’s good to have multiple things you can build on.

Transcript Edited for Clarity