Drs. Leora Horn, Ben Solomon, & Jack West consider whether the data suggest that the better tested PD1 and PD-L1 inhibitors have differences in activity or tolerability or are essentially interchangeable.
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Dr. West: Here at the World Conference on Lung Cancer, like ASCO, immunotherapy was a really hot topic — not a lot of new data here, but still a lot of on going controversies, and one of them, in fact, a featured question at a symposium that I hosted on current debates, is whether these agents are clearly clinically distinct, or largely interchangeable. Do you have a sense of that based on the data, your own impressions, right now?
Dr. Horn: So, the response rates seem similar — it’s hard to gauge between agents because they seem to have different cut points, different assays. I think that there are going to be some differences between a PD-1 and the PD-L1 agents, and some of the clinical experience that I’ve had at our institution is that, PD-1 patients, for the most part, who have come off therapy, I’ve had less patients who have progressed at a later point, and I’ve actually treated one patient who came off a PD-L1 inhibitor, after progression, with retreatment with a PD-1 inhibitor, who then responded. So, I think that there is interesting science that we need to sort out between the way these different drugs act, but it may turn out that there are some subtle differences in the efficacy between the PD-L1 versus the PD-1 inhibitors.
Dr. West: I think these are the kinds of questions we’re wrestling with — for instance, as we get other drugs on the market, will it make sense to treat with a PD-L1 inhibitor after a PD-1 inhibitor, or vice versa, or is there a huge amount of cross-resistance, toxicity differences — pneumonitis really a significant issue with PD-1 but maybe not an issue with PD-L1. What are your thoughts Ben?
Dr. Solomon: Yeah, I think it’s still early days in terms of resolving those questions. I think most of the data, like Leora was describing, are anecdotal now. At a clinical level, response rates and toxicity are broadly similar across the classes. I think there may be some subtle differences that are emerging — I mean there are different targets, PD-1 is a receptor which is on the surface of lymphocytes, whereas PD-L1 is a ligand, which is expressed on the surface of tumor cells, and the ligand can interact with different receptors, and the receptor can be activated by different ligands. So, it wouldn’t surprise me, over time, whether some differences emerge.