Global Outlook on Advanced Nonsquamous NSCLC - Episode 4

Duration of Immunotherapy for NSCLC


Suresh S. Ramalingam, MD: I want to come to a couple of important abstracts that we saw at this meeting. One is the duration of immune checkpoint inhibition. I wouldn’t say we had a definitive answer, but there were hints as to how long the immune checkpoint inhibitor was given. Dr. David Spigel presented this study of nivolumab where some patients received checkpoint inhibition indefinitely and some for a defined duration. Can you walk us through what your thoughts are about that trial and what we should do for our patients?

Benjamin Besse, MD, PhD: The trial was a randomized trial of continued use of nivolumab, or let’s say a watch strategy so that you stop and follow the patient and reintroduce nivolumab in case of disease progression. While the PFS curves are very clear that continuous use of nivolumab after 1 year of nivolumab in the patients with that stability from the drug is better, the overall survival curves, there is a trend for the benefit of continuous nivolumab, but the data are not major.

I think it’s important information, and we will have the data on should we stop at 2 years or go on after 2 years? For me, that really means that we should not stop immunotherapy after 1 year, even in the patient with special response. It definitely will change my practice.

Suresh S. Ramalingam, MD: So, this is a study that was relatively small in size and perhaps not perfectly designed to answer the duration of therapy question, but provide some early hints on what is potentially the duration of therapy.

Giorgio Scagliotti, MD, PhD: Yes. Well, in practice, it’s not changing anything because there are technical issues in that study. They started with more than 1200 patients to end the randomization that had been done in less than 240 or 230 patients. So, it seems to me that probably the most important study to be done is not this type of study, but it’s a study that is looking about the opportunity to continue immunotherapy for those patients who are in CR or PR. And probably we need to do a randomized discontinuation study in those patients with resistance stabilization. That could be another study that will tell us if we need to go ahead for 2 years or we can stop earlier. The other point, we need to factor the activity with the toxicity. There is a minority of patients that are getting some degrees of toxicity. This is something that we need also to consider. I agree with Benjamin that 2 years is probably the right way to move forward.

The other point is that I know that there are people who are reluctant to offer immunotherapy for 2 years. But I truly believe that if we are aiming to make lung cancer a chronic disease, we need to accept the idea of continuing treatment for a long period of time. I’ll make just an example to every one of you. In metabolic diseases when you are started on treatment, you are not stopping treatment. In the diabetic patients, if you are not stopping insulin after 2 or 3 years, then you are going on along with the same treatment for all his or her life. So, consequently, I believe that we should stay with the standard. We don’t have any evidence why we should stop after 2 years, but it is what it is. And this is what we saw in the context of clinical trials, that we need to stay around the results of the randomized clinical studies.

Benjamin Besse, MD, PhD: One point is that the half-life of these drugs—nivolumab, pembrolizumab, atezolizumab—is very long. It’s more than 25 days. And nivolumab is given, at the moment, each 2 weeks. So, for a very long period, it can be a bit difficult for the patient. In my practice, I will tell a patient that it will be a very long treatment, but we can skip 1 or 2 injections from time to time if they want to go on vacation or take 1 month off. I have absolutely no issue with that. So, I think we should continue the treatment, but be very flexible with the patient if they want to skip an injection.

Suresh S. Ramalingam, MD: Right. So, Marina, do you have any specific additional thoughts on this duration issue?

Marina Garassino, MD: No, I totally agree with you. I think that the biggest problem is that for those patients who are in the complete remission. I have some patients still in the CheckMate-017 and CheckMate-057 that are still on drugs after about 4 years or so. I think that in these kind of patients, with the PET scan and the CT scan, which is totally negative, sometimes you have the feeling that maybe you can stop, but we need further data for this.

Transcript Edited for Clarity