Transcript:Mark A. Socinski, MD: Dean, the PD-1 inhibitors in bladder/kidney cancer, tell us what role they may play there, what the data has been so far.

Dean F. Bajorin, MD: In terms of perspective, if you look at renal cell carcinoma, we’ve been using immunotherapy for many years. We used IL-2, and one of the problems with IL-2 is that although we have a 4% long-term survival rate, we had a 5% toxic death rate. It was exactly the same, which is really problematic—not frequently used, selective. We moved on to interferons and, again, poor, in terms of response and benefit. And in the last decade, we have all the antiangiogenic drugs. This was really novel and highly effective. We don’t see much in the way of CRs. We see mostly partial responses. But along comes nivolumab, a randomized trial comparing it head-to-head to everolimus in patients whose disease had progressed after first-line antiangiogenic therapy. We saw some of the similar findings that you see in other diseases. First of all, it was a much higher response rate for nivolumab and the survival was clearly superior in patients who got nivolumab versus those who got sorafenib with everolimus as second-line therapy.

The toxicity is substantially less. In fact, with 6-month improvement of survival—from 19 to 25 months—you had half the toxicity with nivolumab than you did with everolimus. That’s encouraging, and it has the same kind of benefit for all expressors with regard to PD-L1, so you don’t have to use a selection. And as a consequence of that finding, we know it’s an active drug, and now we’re starting to move forward to first-line therapy. It’s happening now, and I suspect these trials would be reporting out very, very quickly.

Mark A. Socinski, MD: In bladder, too?

Dean F. Bajorin, MD: In bladder, it’s a little different story. Actually, nivolumab is active in bladder cancer. At these meetings—at the ASCO 2016—Pam Sharma from MD Anderson is going to present the data from CheckMate-025, and it shows that it’s active. The response rate is 25% in patients who are heavily pretreated for bladder cancer. Now, just looking at that population, the median survival of patients for second- and third-line therapy for bladder cancer is roughly 7 to 8 months. One-year survival is pretty uncommon for the patient population. In this study of 78 patients, the response rate was 25%, basically twice what we would see with chemotherapy in that setting. And the 1-year survival was 50%. So, that’s highly encouraging. We’re waiting for the breakdown with regard to PD-L1 expression, in the mutational load analysis, etc. But the bottom line is, it’s active, and it’s undergoing more in the way of trials.

Pembrolizumab was also active. Actually, it’s been recorded in a phase I study and was 27% in PD-L1 expressors, based on the assay that was just discussed. And now it is in a randomized trial against standard chemotherapy in the United States and standard chemotherapy in Europe, which are drugs that we don’t have.

Transcript Edited for Clarity