"It's really gratifying to see how the field has changed over the last 10 years," says Daniel P. Petrylak, MD.
In this video, Daniel P. Petrylak, MD, discusses the current bladder cancer treatment landscape. Petrylak is professor of medicine (medical oncology) and of urology at Yale School of Medicine and chief of genitourinary oncology at Yale Cancer Center, New Haven, Connecticut.
It's really gratifying to see how the field has changed over the last 10 years. In the early part of the last decade, we only had MVAC or gemcitabine cisplatin, which showed improvements in survival for patients with metastatic disease. But the majority of patients relapsed and progressed. And although we do see a tail to the curve; in other words, about 5% to 10% of those patients treated with chemotherapy, classically, live 5 years, now we've developed new agents such as checkpoint therapy, as well as ADCs, or antibody drug conjugates. The checkpoints were the first ones to be approved; there are 3 that are now still approved for use in urothelial carcinoma, and we have different settings in which they're approved. So for example, pembrolizumab [Keytruda] is approved as a second-line agent after patients have been on chemotherapy. Avelumab [Bavencio] is approved for those patients who respond to chemotherapy, and then we give them maintenance therapy. That showed an improvement in survival over just observation; same thing with pembrolizumab in the second line. I started working with enfortumab vedotin [Padcev]—it's hard to believe—almost 12 years [ago] now. It's an antibody drug conjugate. One of the remarkable things about this drug is that the response rates in first line, second line, and third line are all about 40% irrespective of whether the disease is in lymph node, which actually does better with chemotherapy, or if it's visceral, which includes liver metastases, which classically have been fairly resistant to both chemotherapy as well as checkpoint therapy. In fact, from our experience with phase 1 with enfortumab, we have some patients with liver metastases, who are complete responses and who are 8 and 9 years out. Same thing with lung metastases as well. So long-term survival in the third-line setting, which was unheard of in the past, is now possible. I was a senior author on the EV-301 study, which was a third-line study, which randomized patients to receive standard-of-care chemotherapy, which could have been a taxane or in Europe was vinflunine, or enfortumab vedotin. And we saw a survival benefit, so this drug is now moving up earlier, and the combination of enfortumab plus pembrolizumab is remarkably showing survival of 30 months, where the control arm was 15 months. So it's double the median survival. My opinion is it probably has done that by now the fact that we can treat that disease that we couldn't treat before - the liver metastases, the visceral disease. The other thing, too, which I think is remarkable about the combination is that the duration of response has been more than a year, and time to progression is about the same. So this is showing us that there's some interaction between pembrolizumab as well as enfortumab, which is unique. I think it's the first example of true synergy. So the question is going to be now, what are we doing second line for those patients who've, unfortunately, not responded to enfortumab-pembrolizumab? Do we go back to standard chemotherapy? What's the right sequence that we should be using in these patients? There are a lot of important research questions. And then of course, how do we develop new drugs in this new world? If you have survival of 30 months, you have to start looking at other surrogate end points to least assess activity, such as progression-free survival, because it's going to take a long time to get drugs approved.
This transcription was edited for clarity.