Transcript

Hello, my name is David McDermott. I'm Chief of Medical Oncology at Beth Israel Deaconess Medical Center here in Boston. I'm here to talk about the KEYNOTE-427 trial, which was presented this year at ASCO as an update for last year's presentation.

So the KEYNOTE-427 trial was actually a trial of pembrolizumab, or a single-agent PD1 blockade, in untreated patients with advanced kidney cancer -- a large group of clear cell patients and an even larger group of non-clear cell patients.

It was unique in several aspects. Taking a step back, I think the treatment for advanced kidney cancers changed dramatically in the last couple of years, moving PD1 blockade into the frontline.

It's been moved to the frontline in combination with the old standard of care of VEGF blockade and it's produced significant improvements in outcome. But until the KEYNOTE-427 trial was reported out, we really didn't have a sense of what single-agent, PD1 blockade would give us in untreated patients, so we learned a lot from this trial.

I think one of the main things we learned from KEYNOTE-427 was a lot of the clinical benefit that we see with PD1 and VEGF combinations and PD1 and CTLA-4 combinations is actually driven by PD1 blockade alone. So it helps us put those results of combination, PD1-based combination therapy into some context.

For example, in cohort A of the study, the response rate was an impressive 36-percent with the single-agent pembrolizumab, which was actually better than we expected.

And in the larger cohort B, the response rate was 26 percent, once again, better than we would have expected and very different from what the conventional wisdom was about the old forms of immune therapy, like cytokine-based immune therapy typically not showing most activity in non-clear cell patients. Here we saw a healthy response rate.

I think one of the other aspects that we've seen this year with the update is the durability of that benefit. So now, with over an extra year of follow-up, we're seeing a more ongoing response, which is very encouraging. It's obviously what the patients want. They want to see benefit and then they want to see that benefit persist.

And not only did we see that in some of the patients, but we also saw benefit in patients who actually stopped treatment. In fact, I think it was about 40 percent of the patients who had a major response, were able to continue that response for over six months after stopping treatment. So 15 out of 40 responders, or 38 percent, fell into that category.

I think also we were seeing responses across all IMDC risk groups regardless of the PD-L1 status. Although if your tumor was PD-L1-positive, you were more likely to benefit from the treatment.