Corey J. Langer, MD, FACP: With the TMB analysis, we’ve certainly concentrated on CTLA-4 inhibitors with PD-1 and PD-L1 inhibitors. But there are many other agents out there. Earlier, Ben alluded to the potential benefits of angiogenesis inhibition. There have been phase I and phase II studies now looking at pembrolizumab with ramucirumab in a relapsed population. Folks have been platinum exposed with response rates in the 30% to 35% range. Granted, it’s not the 60% that we’re seeing in the frontline setting, but it looks better than that 16% to 18% to 20% response that we typically see with single-agent immuno-oncology. There is tremendous interest, of course, in moving that forward to the frontline setting.

We’ve seen similar data looking at epacadostat, an IDO inhibitor, with pembrolizumab—again, a 35% response rate. There have been negative data in melanoma, but I caution our routine extrapolation from one disease to another. I think these agents really need to be studied separately.

Similarly, there have been studies of necitumumab with immuno-oncology agents—again, generating response rates of 30% to 35%. So, the door is wide open. There is a whole fleet of agents, other immunotherapy agents, that can be combined with these approaches. In both the second-line and, potentially, in the first-line setting, the door is wide open.

Benjamin P. Levy, MD: Some of these combinations are rooted in some biological rationale, and some of them aren’t. I’m actually OK with that. In some ways, we’re throwing darts at a dartboard to see what sticks. I think that’s what we have to do right now. The only problem is that we have so many trials with perhaps too few patients, and I think we need to be mindful of which trials really have strong scientific rationale and which ones don’t. I think that’s important to consider. But the door is open. I think we’re going to learn a lot.

Karen Kelly, MD: Right. It’s also about trying to find biomarkers. That is going to really be crucial as we move forward. Remember, not everybody benefits. The curves, particularly the progression-free survival curves, still go down. We really do need to try to find better biomarkers so that we can individualize treatment. Then, when you’re spending the money, you know you’ve added value.

Corey J. Langer, MD, FACP: And that will help drive down cost, as well.

Karen Kelly, MD: Exactly.

Corey J. Langer, MD, FACP: I agree. About a third of patients with small cell cancer seem to have very high TMB, which is no surprise, considering their smoking history. And there, ipilimumab/nivolumab seems to have had particularly high response rates—progression-free survival and overall survival. So, is there a way to really identify those folks who are going to be on the tail of these curves and not expose individuals who are really not going to benefit?

Mark A. Socinski, MD: I’m going to have to revise my thinking. I’ve always tried to be the teacher of “We want to get the right drug to the right patient at the right time.” I will need to revise that to add “at the right cost.”

Karen Kelly, MD: That’s good.

Mark A. Socinski, MD: Yes. Well, I’d like to thank my colleagues. This has been a very informative discussion. I hope this has been helpful to you. Thank you for all of your contributions. On behalf of our panel, we thank you for joining us. We hope you found this Peer Exchange^® discussion to be useful and informative.

Transcript Edited for Clarity