FDA Approval of Durvalumab for Advanced Bladder Cancer
David I. Quinn, MD
David I. Quinn, MD: For durvalumab, we had seen in an early phase II study that there was significant activity based on response rate that was durable in urothelial cancer. And these were patients who had been relatively heavily pretreated. The subsequent complimentary phase II study 1108 confirmed that activity, and led to the FDA moving the status of the drug from breakthrough status to accelerated approval so that it could be used.
Therapy, as with the other checkpoint inhibitors, is given intravenously every 3 weeks, and it’s extremely well tolerated by the patients, so it has a similar profile to the other checkpoint inhibitors. For people who are now potentially going to use this agent in urothelial cancer, it doesn’t hold any kind of mysteries or unusual toxicities. Most of our patients see a little bit of fatigue and they have no other side effects really very much to complain of. They’re often low-grade things as they’re being treated for.
Importantly, there are autoimmune-type phenomena that occur where various parts of the body can become inflamed. We can occasionally see colitis, pneumonitis, elevated liver enzymes as an older immune hepatitis, and then occasionally alterations to endocrine function, most particularly hypophysitis with loss of secretion of cortisol and thyroid hormone that needs to be supplemented. This is rare but when it occurs, it’s serious. So, in terms of the day-to-day management for medical oncologists who have used the other checkpoint inhibitors, either in urothelial cancer or in some of the other indications, this new drug does not hold any mysteries.
The response rate that we saw in the studies is within the same realm as the other agents. And interestingly, it does seem to congregate a little more tightly with their PD-L1 marker in tissue. We’re going to need to see phase III studies to work that out a little more, and you don’t need to do the marker to give the drug. And so, from that perspective, you can treat patients who are platinum experienced and have then progressed with the agent without too many difficulties.
Durvalumab we’ve used across a series of different histologies and primary sites, and so we have experience in melanoma, lung cancer, and urothelial cancer at our site. And this varies. Sometimes we’ve give it in combination. We’ve certainly seen responses. We have not really seen significant toxicity to date. Nothing unexpected. So, our experience is good with the agent. And I think we’ll now see how it’s developed further in urothelial cancer.