Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Activity and predictors of response to immune checkpoint inhibitors in previously treated UBC
4:39 minutes.
TRANSCRIPTION:
DR LOVE: Can you talk a little bit about the other data sets we have for other checkpoint inhibitors, maybe starting out with nivolumab? DR GALSKY: So nivolumab has been studied in a large Phase II study. And this study enrolled patients similar to the atezolizumab data set, patients who had received platinum-based chemotherapy and then subsequently had disease progression. And the response rate to treatment in that study was 19.6%. The responses were quite durable again, consistent across PD-1/PD-L1 inhibitors and consistent across indications. And the safety profile was really quite similar as well. DR LOVE: And pembrolizumab? I know there’s some data presented recently. DR GALSKY: Yep. So pembrolizumab, the only data we had for pembrolizumab until just a few weeks ago was an expansion cohort of a Phase I study, which was really quite small. And that showed promising activity with pembrolizumab in patients who had received prior chemotherapy. And that was one of the data sets that really led to enthusiasm for this approach in metastatic urothelial cancer. So based on that data, a Phase III randomized study was initiated. And this study compared pembrolizumab with standard-of-care chemotherapy. And that standard-of-care chemotherapy could be a taxane or, in countries where vinflunine was available, patients could receive vinflunine. What we do know from the presentation is that the likelihood of achieving an objective response to treatment was significantly higher in patients who received pembrolizumab. The overall survival was better in patients who received pembrolizumab. And this included all patients, and patients were selected — or, I should say, the subset of patients who had increased PD-L1 expression. In addition, looking at the side-effect profile, pembrolizumab appeared to be much better tolerated than standard chemotherapy. DR LOVE: So yes, I guess the other checkpoint inhibitor we’ve heard about is another anti-PD-L1 agent, durvalumab. What do we know about that in bladder cancer? DR GALSKY: So we have data from a fairly large experience with durvalumab in patients with, again, chemotherapy-pretreated metastatic urothelial cancer. And if you look at that data set and compare it to the other data sets, the response rate seemed to be a bit higher. However, that has to be interpreted with caution for a couple of reasons: (1), because the sample size is still smaller than the sample sizes that we have with these other drugs, and so the confidence intervals are wide. And the other issue is that patients were initially selected based on PD-L1 expression, and then all comers were allowed. And so it’s a little bit of a mixed population and might have been enriched a little bit for response. DR LOVE: Globally, when we look at all these trials and strategies, what do we know about predictors of benefit or predictors of response and, particularly, PD-L1 assays? DR GALSKY: So the PD-L1 data is really across the board, like it is in many cancers. For some trials, like the atezolizumab data in the chemotherapy-resistant population, you do appear to enrich the likelihood of response to treatment by using an assay testing for PD-L1 expression, similarly, with the nivolumab data, a similar finding. However, in both of those data sets, even for patients with no PD-L1 expression, the response rates are still as good to better than what we have with standard chemotherapy. So while one could probably enrich the likelihood of response, that hasn’t translated into an impact on clinical practice, because even in patients without expression, these treatments probably still represent better options than the treatments that we’ve had available before. The data from the randomized setting with the pembrolizumab trial is incredibly important, because it does show that the hazard ratio in terms of improvement in survival is even more impressive in the PD-L1-selected group. But in patients who were not selected, the all-comer population, there is still a significant improvement in survival, which appears to be clinically significant as well. |