New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
Checkpoint inhibitor-associated toxicities
2:10 minutes.
TRANSCRIPTION:
DR LOVE: I was going to ask before, we talked about pneumonitis with immunotherapy. And it doesn’t seem to be that big of a problem, for example, in melanoma. But in lung cancer, you’re talking about people who smoke, people with chronic lung disease. DR LANGER: People who have been radiated to the chest, which is a big concern. DR LOVE: How is it playing out there? DR LANGER: Many of the studies exclude folks who have had any history of radiation pneumonitis, even if they’re completely over it and they’re off steroids, which I think is — when we look at the ultimate indication for these compounds, assuming they get approved, which I think we all are, there’s going to be a lot of restrictions and a lot of unknown territory. DR LOVE: Dave, any thoughts about this issue of pneumonitis in lung cancer? DR SPIGEL: Yes. So far in the reports we have on all the agents, it’s not been a problem with the anti-PD-L1 programs. And that may have something to do with PD-L2 in the lung and how it interacts with PD-1. So the problem was nivolumab. When nivolumab was first developed, there were 3 patients at Hopkins who had a problem and led to fatalities. I struggle with pneumonitis. It’s not quite QTc stuff, but I’m always very skeptical about what is pneumonitis, how do we confirm pneumonitis? I’ve spoken with 2 of the investigators at Hopkins. And they feel very strongly this was a drug effect, and they tried everything. I do, just speaking of toxicity, I often talk to patients about how these drugs are very safe, but they have different toxicities, and we need to be aware of that. And one toxicity that can be troubling, particularly for patients who are doing quite well for extended periods, can be the colitis. So you can have patients doing quite well who develop ipilimumab-type colitis that forces them to come off the agents. DR LOVE: With anti-PD-1? DR SPIGEL: With all of these agents. DR LOVE: Really? DR SPIGEL: And what’s interesting is it’s anecdotal now, but those also are the patients who’ve had the best responses, obviously been on therapy the longest. So it’s almost like you have to run through the gauntlet to get the best benefit. But it’s a real issue. We struggle with ipi. When ipi was being developed across tumor types, that was a real scare for everybody. So these drugs are not completely void of that toxicity. |