Nuances in Treating Advanced Lung Adenocarcinoma - Episode 8

The Potential for Adjuvant Immunotherapy for NSCLC

Transcript:Mark A. Socinski, MD: How does the panel feel about the issue of adjuvant treatment? We’ve talked about immune-related toxicities. Obviously, the surgical population lives a lot longer. What we know about these immune-related toxicities is that they can be very delayed in their occurrences. Is there concern either with monotherapy or how people feel about I-O combinations in the adjuvant setting? Any thoughts about risk benefit in that population?

Mark G. Kris, MD: It’s goals of care. If you have the potential to increase the cure rate, then risk becomes much more acceptable. Look at folks who undergo a bone marrow transplant—talk about a risky situation. Why do folks accept that? They do that because it increases their rate of cure, and I think people will do that here, too. Obviously, we need to be very vigil in these patients and if they have long survival, we have to be very careful. We have to use everything we’ve learned about how to manage these side effects and be very cognizant of them. But I do think that the chance of cure justifies more risk.

David R. Spigel, MD: Yes, I agree with you, Mark. You do start to wonder how you’re going to get these combinations—these other 900 clinical trials that are in the advanced stage settings across cancers—into earlier stages when these trials take so long to get done. I think people don’t want their cancer coming back. They’re going to take that risk, that’ll probably be manageable for most patients.

Mark G. Kris, MD: But there is a way to go there though: neoadjuvant therapy.

David R. Spigel, MD: Yes, I was going to bring that up. I’m blown away. I know the numbers are tiny out of Johns Hopkins, and maybe some of your centers are participating in this. To get 2 doses of nivolumab for early stage cancer and have what’s defined as a major molecular or pathologic response, less than 10% of survival in cells, in about half of your patients—it really makes me start to question our radiographic responses. Because for that same group, we probably would have measured a response rate of about half of that, and then when you look at it in the microscope, it’s doubled. So, what does that mean in the advanced setting? All these studies are looking at response rates and PFS. Are we really able to measure the benefits of these drugs? That study is really interesting, and there are many others that have launched now. I think we’ll learn a lot more.

Ross Camidge, MD, PhD: To be fair, that’s 22 patients with a 40% pathological response rate.

David R. Spigel, MD: I know.

Mark G. Kris, MD: But in the advanced stage, sadly, those folks are unwell, and it’s really clear when these drugs aren’t working, at least in my experience. It’s pretty rare when they’re working, and we just can’t appreciate it. Sadly, they’re not working well enough for a lot of people and the quickness of their illness growth and their symptoms tells you that. It’s a different story here. But that’s the beauty of pathologic response at the time of surgery—you know exactly what happened.

David R. Spigel, MD: Yes. I think if it as, if it’s only seen in this study, it’s just a numbers game. But if it’s seen across these trials, then really we have to start learning more about what’s happening in our advanced-staged patients.

Mark A. Socinski, MD: It certainly provides a lot of enthusiasm for a neoadjuvant approach. But, as Ross points out, those numbers are small, but certainly worthy of further trials.

David R. Spigel, MD: It’s good enough for accelerated approval probably.

Mark G. Kris, MD: It gets to your point about giving a drug for a long period of time that may not be working. We were involved with the atezolizumab trial—Ross was involved as well, in neoadjuvant. But it’s also a potential adjuvant therapy, depending on the benefits seen in the adjuvant setting, and, of course, the safety there, too.

Transcript Edited for Clarity