Checkpoint Inhibitors for Relapsed or Refractory NSCLC

Transcript:Mark A. Socinski, MD: Jared, the third agent we had approved in this space was atezolizumab, and it was really on the basis of the phase II POPLAR trial, as well as the phase III OAK trial. Could you just briefly walk us through that data set?

Jared Weiss, MD: The POPLAR trial was a randomized phase II; the OAK trial, a randomized phase III. Both were docetaxel versus atezolizumab, and both showed the exact same finding: a hazard ratio of 0.73 for overall survival. I guess OAK read POPLAR before being reported, but they had exactly the same result and very similar efficacy and toxicity profiles to what we had seen before in the comparative studies with nivolumab and pembrolizumab.

Mark A. Socinski, MD: So, it’s interesting that the 3 agents we have took slightly different approaches: nivolumab, a histology-based approach with CheckMate-017 and CheckMate-057, being squamous and nonsquamous respectively; with pembrolizumab, a PD-L1 biomarker strategy; and with atezolizumab, it was an all-comers strategy, right? And all in the same trial. The issue is that atezolizumab is the first anti-PD-L1. Does that make a difference versus anti-PD-1?

Jared Weiss, MD: There are theoretical reasons why it could and perhaps should make a difference. But if you look at the clinically available data in this context, as well as other cancers in context, there’s really no hint that it actually does. The toxicity profile looks nearly like it is copy/paste. The efficacy profile looks nearly like a copy/paste. So, at least in terms of single-agent use, atezolizumab looks more similar than different from nivolumab and pembrolizumab. What I’m curious about is to see—who knows how many combination trials we have going on—in the combination trials with atezolizumab and durvalumab, if that story continues to play through, of similar efficacy and tolerability.

Mark A. Socinski, MD: The issue with—I’m sorry, I got thinking of 3 different things at the same time. So, everyone on the panel has used atezolizumab?

Panel: Yes.

Mark A. Socinski, MD: And your experiences as a group?

Mark G. Kris, MD: Copy and paste.

Ross Camidge, MD, PhD: Pepsi-Cola and Coca-Cola so far.

David R. Spigel, MD: Although, I have one story of a patient who has been on atezolizumab on a trial, and they had to come off after being on it for about a year and a half because he had a lesion that we wanted to radiate and the study wouldn’t allow it. So, he came off it. To make a long story short, we had to put him back on another agent. Atezolizumab wasn’t approved, so I put him on nivolumab. And after about 2 treatments, I said, “So, Mr. Smith, it’s the same thing, right?” And he said, “No, it’s very different, very different.”

Mark A. Socinski, MD: Really?

David R. Spigel, MD: So, I don’t know that we have that many patients who’ve been on different agents who can tell differences, but my guess is now that these drugs are on the market and we have no data to say that you should do this, there might be some switching like this that happens for various reasons—maybe an insurance reason or some other reason. I’m wondering if there will be differences that patients notice.

Mark G. Kris, MD: I had the same scenario though, exactly—a clinical trial, but the patient said there was absolutely no difference, other than having to come in more often.

David R. Spigel, MD: Yes.

Jared Weiss, MD: Well, that’s the 1 difference here. There are practical differences in how these drugs are approved, even if a lot of us aren’t convinced that they’re more different than, say, Coke and Pepsi. Nivolumab is approved in the second-line setting and is an every-2-week drug regardless of PD-L1 status. Pembrolizumab is every 3 weeks requiring PD-L1 positivity, and atezolizumab is every 3 weeks regardless of biomarker result. And those do influence when you can prescribe them vis-à-vis payers. For demographics where the travel distance is long, that every-3-week dosing can matter to some patients.

Mark A. Socinski, MD: So, is that the deciding factor? Are there cost differences between the agents that we know of?

Jared Weiss, MD: I’m not aware of any real cost difference between these agents. My understanding was that they all come in at roughly $12,000 a month. I’m not an economist regarding this stuff, but something like that—regardless of which you use—to the patients, it can matter. I hand out a lot of gas cards from our local advocacy organization, because people have trouble affording the gas to come into my cancer center. In that context with that kind of population, people traveling either because they can or because they have to, it matters a lot.

Mark A. Socinski, MD: You very nicely summarized the 3 drugs in the second-line space. Obviously, only 1 of them is dependent on PD-L1 status. How does the panel feel about the use of PD-L1? I know it’s kind of artificial now, because we all agree we should check it in the first-line setting. Prior to that, we didn’t necessarily do this to administer second-line therapy. In fact, most people didn’t do it. We’re going to come back and circle around to the KEYNOTE-21G trial issue in a moment. But what’s the message if you’re PD-L1 negative in the second-line space? Does that dissuade anybody from using these agents? Or, since 2 of them are agnostic to PD-L1 status, are they standard of care?

Jared Weiss, MD: It’s not just the approval. It’s that the PD-L1-negative patient, as measured the way we’re currently measuring them, did receive benefit, and there are now 3 major efforts evaluating them.

Ross Camidge, MD, PhD: I think the key thing is, what is your alternative? So, if the alternative is single-agent docetaxel, which is not a great drug, then any of these drugs, even though the benefit may be relatively low in those who have PD-L1 expression, are still better than the alternative. Now, if we get a better cytotoxic sitting in there or something else, that comes up for debate again.

Transcript Edited for Clarity