Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Overview of immune checkpoint blockade in metastatic UBC
4:30 minutes.
TRANSCRIPTION:
DR LOVE: Can you just kind of provide an overview of which checkpoint inhibitors have been looked at in trials, in which lines of therapy, and kind of where things are heading? DR PLIMACK: Sure. Sure. So everyone’s diving in all at once. There are five PD-1 or PD-L1 inhibitors being looked at in bladder cancer. Atezolizumab was the one that was approved first, and that was based on single-arm data from their large Phase II trial. Pembrolizumab is the first to show us randomized data compared to chemotherapy showing a benefit, and so we expect that that will be available shortly as well for bladder cancer, based on those very impressive results. DR LOVE: And again, that’s second line? DR PLIMACK: All of these are postplatinum, so second line. A comment about second line is, second line in bladder cancer is defined as having had platinum for metastatic disease and then progressed on it or having received platinum perioperatively and recurred within a year. So many patients on all of these trials, it may have been 6 months since their last treatment if they got it perioperatively and then recurred. DR LOVE: Interesting. And what other checkpoint inhibitors? DR PLIMACK: Right. So going back to the PD-1 agents, we talked about atezolizumab. We talked about pembrolizumab. There are many others, but I’ll talk about 3 others that are being investigated. Nivolumab presented data at ASCO, single agent, and avelumab presented early data as well. And then there’s another, durvalumab, that’s being looked at in bladder cancer. All of these have presented, so far, single-arm data for single agent postplatinum. Some have showed us front-line data. So pembrolizumab and atezolizumab have both showed us front-line data in the metastatic setting. What’s interesting is, those response rates are similar to what we see in the second-line setting with both those agents. So we’re not seeing a dramatic increase in response rates going earlier, but certainly a nice survival benefit compared with historic controls. Again, we don’t have any randomized data yet in the front-line setting. DR LOVE: It’s actually, to me, encouraging that it’s not lower, because I’ve heard people say that somehow maybe chemo might prime patients for PD-1 or checkpoint inhibitors. DR PLIMACK: Yes. I mean, I think based on this new antigen release theory or based on the idea that mutational load portends to better response, you may have both of those factors may be augmented after chemotherapy. Honestly, I don’t think we know. I think the argument to use these drugs earlier is that when they work they work well, and they’re well tolerated. Why not give a patient a chance at that excellent outcome? Again, not everyone achieves it, but give them a chance at that first rather than putting them through chemo, where everyone feels at least a little bit crummy on chemotherapy. DR LOVE: Yes. I was actually going to ask you about that in a second. But first, in terms of these different checkpoint inhibitors, some are anti-PD-L1 — for example, atezolizumab — nivolumab/pembrolizumab, anti-PD-1. I think durvalumab is anti-PD-L1. Any difference between any of these that you can pick up? DR PLIMACK: I don’t think there’s really any difference that we can measure or see based on the data sets we have between any of these inhibitors. I think they all work on the same axis. They all essentially do the same thing. There may be slight differences in toxicity profile, but we’re going to need more data to really sort that out. I think they’re very similar. And, I think, also similar combinations are being looked at as well with all of these. So we’re getting a lot of trials with a lot of data, but many looking at similar questions with different drugs. DR LOVE: The dynamic that kind of seems like it’s getting played out with checkpoint inhibitors in other cancers — for example, lung cancer — is, even though you ask investigators and they go, “We can’t tell the difference yet,” the reality is, it’s the trial data that they generate that we kind of have to go by. So pembrolizumab comes out in the first line in lung cancer, and it worked. Nivo doesn’t. They start using pembro. DR PLIMACK: Right. That was a fascinating clinical trial development. I think all of us were watching the lung data as that emerged. And again, I don’t know that anyone has a good explanation for that finding. But we’re in the same boat in bladder, where we’re looking at similar drugs in similar settings. And exactly as you said, we’ll see what the trial data show. |