Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Rationale for the use of immune checkpoint blockade for RCC
3:58 minutes.
TRANSCRIPTION:
DR MOTZER: When I joined faculty at Memorial back in the 1980s, the 2 malignancies that were thought to be the best targets for immune therapy were melanoma and renal cell carcinoma. And that was largely due to a phenomena of spontaneous regression that was seen with both tumors and also the activity that had been reported with interferon, an immune modulator, and then subsequently with interleukin-2. So it’s more been on clinical evidence and historical evidence. With regard to the more recent biology, renal cell cancer does express PD-L1. Originally, when PD-L1 was looked at as a prognostic marker across tumor types by the group at Mayo Clinic, one of the tumors they looked at initially was kidney cancer. And so kidney cancer, PD-L1 was a prognostic marker of a bad outcome. But other than that, there isn’t really any — we need more information regarding the underlying biology. People these days are looking at mutation load now as a predictor for better outcome to checkpoint inhibitors. In melanoma and in lung cancer, there’s been some suggestion that if the tumors have a higher mutational load or a higher load of these neoantigens, then they are better targets for immunotherapy. In kidney cancer, we and other people are looking at that. But we don’t have the information yet in this disease. DR LOVE: What’s the current thinking in terms of smoking and renal cell cancer? And is there a correlation? For example, in lung cancer you see more responses in smokers. Has that been looked at with renal cell? DR MOTZER: So in terms of risk factors for kidney cancer, the one that’s been the most well established is tobacco use. There were estimates that probably about 30% of the cases diagnosed in the United States were associated with tobacco use. In the studies with the checkpoint inhibitors, though, to the best of my knowledge we haven’t been able to show a difference in outcome as to whether the patient’s a smoker or not. DR LOVE: So maybe we can talk a little bit about the clinical research evidence that’s available right now, both with single-agent checkpoint inhibitors and, as you were saying, some of the combinations. I was just flashing. I think it was Chuck Drake from Hopkins who presented a case at one of our conferences of — I think it was the first patient who got nivolumab 8 years ago, who’s still in remission. So I don't know when the research started, but what do we know at this point? DR MOTZER: The first study was that Phase I study that Chuck Drake participated in. That was a Phase I trial, and then it expanded into different cohorts. And kidney cancer, lung cancer, melanoma were the 3 main targets. And so in that particular series, just at last year’s ASCO, David McDermott did report on long-term follow-up. And there are a few patients on that that are still in remission on checkpoint inhibitors, but it’s not a high number. We did do a large randomized Phase II trial of nivolumab, and then more recently the Phase III trial comparing it to everolimus. So, I mean, we’re looking for the tail on the curve to that and what the tail of the curve is. And I think probably the best indication will be with longer follow-up from the pivotal trial compared to everolimus, to see if there are actually patients being cured. I don’t think we know that right now, other than seeing anecdotal cases that are doing well for a long time. |