Mark Socinski, MD: Roy and Stephen, what do you do in your own practice? Do you have a preferred agent?
Roy Herbst, MD, PhD: Atezolizumab was there first, and all else being equal, the drug there first usually gets more share. We’re using mostly atezolizumab now. I didn’t see anything in the data to switch. I will say the pembrolizumab data look very close. What it tells me is that we need a better biomarker here. The fact that all these trials are so close, it tells you that we have a population that’s heterogeneous, and some are probably benefitting more than others, and if you take a mixed population, you're going to see results like this. It’s great for patients, it’s clearly better than what we were using before, but we’re using atezolizumab at Yale [Cancer Center].
Mark Socinski, MD: Steve, agree?
Stephen Liu, MD: It comes down to comfort. IMpower133 was presented in 2018, which was approved March 2019. Durvalumab was approved in March 2020. I think what might have changed it, if we had seen the third arm in CASPIAN, the tremelimumab arm, showing any benefit in survival, then that would have been a combination to pursue. But as you saw at ASCO [the American Society of Clinical Oncology annual meeting], the addition of tremelimumab did not improve survival over just chemotherapy alone. [Atezolizumab] and [durvalumab] both improve survival, And both are reasonable options. I didn’t see a compelling reason to change. CASPIAN, [durvalumab] is given every 4 weeks. We also have FDA approval for [atezolizumab] to give every 4 weeks. It comes down to comfort for me, and I’m still using atezolizumab.
Mark Socinski, MD: Roy, you mentioned we did see at ASCO the third arm of the CASPIAN trial, which was the durvalumab/tremelimumab arm. The interesting thing to me is that there didn’t seem to be any optimism about that combination, and I think the tremelimumab was stopped at a certain point. And the overall survival curve with continuing durvalumab alone eventually caught up with the arm that had only durvalumab in it. Roy, what are your thoughts, any hope for anti–CTLA-4 inhibition in this setting?
Roy Herbst, MD, PhD: I would say not. We already knew from trials with ipilimumab years ago, our colleague ran some of those trials way back when, that there was no real benefit with ipilimumab CTLA-4. And here, adding durvalumab clearly adds toxicity, but unfortunately, no benefit, as you mentioned. I think if there are going to be combinations in small cell lung cancer—and there have to be, because these data, while good, are clearly not a home run yet—we’re going to have to look at other aspects of the immune system and try to scientifically understand why there is some primary resistance to these agents. For now, I would stay away from the CTLA-4 inhibitors. That brings the grade ¾ toxicity up to the 40%-plus range, which is high in these very sick patients.
Mark Socinski, MD: Roy, you brought up before the issue of biomarkers. Obviously, in non–small cell [lung cancer], we routinely measure PD-L1. Any role for that in small cell?
Roy Herbst, MD, PhD: I think yes. The problem is with PD-L1 both in small and non–small, Mark, is measuring it accurately. It’s hard enough to measure in non–small cell where you get good pieces of tissue and there isn't crush artifact, and so forth. In small cell it’s hard to get good core biopsies and really measure it accurately. I think it’s a measurement issue, but I think PD-L1 probably has some role but we've not seen it so far. TMB [tumor mutational burden] could certainly be useful. There are a lot of data recently emerging with whole exome TMB, looking at 175 mutations per megabase in some of the data with pembrolizumab. I wonder if that could someday be used with small cell. All these need to be incorporated in the trials. Perhaps all of the groups that have done these trials could collaborate and pool their data sets to look at this.
Transcript Edited for Clarity