Investigator Perspectives on Emerging Concepts in the Management of Genitourinary CancersAtezolizumab in advanced bladder cancer
4:02 minutes.
TRANSCRIPTION:
DR PETRYLAK: So atezolizumab is an anti-PD-L1 antibody that has shown activity in patients with metastatic urothelial carcinoma, breast cancer, lung cancer. It basically blocks the inhibition of the immune system. And it’s a checkpoint inhibitor. And there have been a number of different drugs that have been tried in that particular space, either anti-PD-L1 or anti-PD-1. DR LOVE: And I guess this is an anti-PD-L1 — DR PETRYLAK: Correct. DR LOVE: — agent, as opposed to, for example, people are very familiar with nivolumab and pembrolizumab. They’re anti-PD-1. What I’ve heard in terms of mechanism is the anti-PD-L1 agents, like this one, bind the ligand. DR PETRYLAK: Correct. DR LOVE: Whereas, the others bind the receptor? DR PETRYLAK: Exactly. DR LOVE: So far, it kind of seems like they’re pretty similar in different tumors. Any way to distinguish them? DR PETRYLAK: So far, no. Theoretically there’s less toxicity, pulmonary toxicity, with the PD-L1 drugs, but there has not been a good head-to-head comparison of the two. DR LOVE: Interesting. And how often is the drug given? DR PETRYLAK: The drug usually is given every 3 weeks. DR LOVE: Hmm. You’ve been very much involved with the research on this agent. Can you talk about specifically the trials that have been done, what they’ve shown and what’s been seen with other PD-1 checkpoint blockade? DR PETRYLAK: So initially, the excitement was generated from a Phase I trial. That’s been presented, originally by Tom Powles. That was written up in Nature. And then we presented some follow-up data at ASCO last year. And basically, in that trial we demonstrated that the PD-L1 expression was important to response and subsequent survival. Those patients who were strong expressers of PD-L1 had about a 50% response rate. Those who were weak expressers or nonexpressers of PD-L1 had about an 11% response rate. Jonathan Rosenberg presented the Phase II experience, 311 patients, at the ESMO meeting this year. And the response rate was somewhat lower. It was 27% overall. And it did seem to trend toward a better response in the PD-L1-positive versus the -negative patients. It’s too early to determine what the overall survival is for the 2+ and 3+ expressers, but the median survival for all patients, including the nonexpressers, was 7 months. The PFS is about 2 months overall. DR LOVE: What about the duration of response? Of course, a lot of the excitement in the other tumors has been the prolonged duration. Have you had enough follow-up to see what it is in this situation? DR PETRYLAK: The only long-term follow-up we do have is from the Phase I trial. And we have not yet reached the median duration as of our presentation last year. And interestingly, if you’re PD-L1-positive or -negative, it doesn’t matter. If you respond, you respond for a good, durable period of time. IHC status in the immune cells really does not correlate with the duration of response. And you could see a very similar early response pattern in the Phase II trial — that, again, if you respond, you respond well. DR LOVE: And have you had any patients — because you hear these stories with other tumors — who had the treatment discontinued for whatever reason, toxicity or any other reason, who remain in response? DR PETRYLAK: We have not discontinued on our patients at this point. If they’ve progressed, we’ve discontinued them. But we have not discontinued anybody who has been responding. DR LOVE: Do you have patients who have had responses, for example, more than a year? DR PETRYLAK: Yes. Yes. DR LOVE: What’s the longest that you’ve observed yourself? DR PETRYLAK: The first patient we treated on a Phase I trial, he started in March of 2013. And he progressed in January of 2015. |