Lung Cancer Update, Issue 3, 2016 (Video Program) - Video 28JAVELIN trial: Efficacy and safety of the anti-PD-L1 antibody avelumab in unresectable advanced mesothelioma
2:49 minutes.
TRANSCRIPTION:
DR BLUMENSCHEIN: We know that PD-L1 is expressed in mesothelioma, and that was part of the rationale from enrolling patients on this trial. It was about a 50, 54-patient study, single arm, and patients received avelumab, which is a monoclonal antibody, IgG1, targeting PD-L1, which is on the surface of the tumor. Patients were enrolled independent of their PD-L1 status. And what they were looking for was indication of activity, measured by response, progression-free survival and then also expression of PD-L1 to see if they could correlate that with outcomes. They did see a response. Response rate was about 9.4%. And then the interesting thing was, when they looked at outcomes by PD-L1 status — and they had tissue of the 50-odd patients, they had tissue in about 39 that they could utilize to evaluate PD-L1 status. Two of the patients who responded were PD-L1-positive, and 2 of the patients who responded were PD-L1-negative. So a little bit clouding of the picture there. But again, it may come down to the fact that the testing with PD-L1 is not an exact science. DR LOVE: The other issue that, of course, it comes with checkpoint inhibitors and it’s kind of hard to say this with just a few patients, would be duration of response. Anything you can say at all about that right now? Not just with this agent, but in general? DR BLUMENSCHEIN: So what they reported from that trial, in particular, was the PFS benefit of about 17 weeks versus 7 weeks for patients who were PD-L1-positive. But then when you look at it at about 20 — I think it was 24 weeks when they took a look back at the progression-free survival, they were equivalent. They were 39 and 40%, respectively. So that didn’t correlate over the long haul. I think what this study represented was just an opportunity to demonstrate activity. And they’re going to be building upon this, looking at combinations with CTLA-4, which can upregulate PD-L1, and potentially turn a “cold tumor” into hot one that might benefit from anti-PD-L1 therapy. Plus, there will be combinations with chemotherapy and also with vaccines. And potentially with anti-mesothelin ADCs as well. But to get to your point, the duration of response, those patients who respond, especially in the non-small cell lung cancer space, have very durable responses. In the Phase III studies that were reported out with nivolumab in the second-line setting, duration of response was on the order of 18 months or 17 months. Quite long. So when these responses occur, they are durable. DR LOVE: But can we say anything about duration of response with mesothelioma at this point? DR BLUMENSCHEIN: That was a small trial. It was one of the largest studies done with immunotherapy, aside from the tremelimumab trial, but it was only 50-odd patients. And I don’t think we have enough data to really comment on that. There were 5 responses. So I think we need more time. |