So the Bladder JAVELIN 100 study is a study which investigated avelumab versus best supportive care as maintenance therapy after front-line chemotherapy. The front-line chemotherapy was Gem-Cis or Gem-Carbo, and patients had to have a response or stable disease with frontline chemotherapy. So essentially, it's for those patients who you give chemotherapy to, and then at the end of chemotherapy, provided you responded or had stable disease with chemotherapy, you either get maintenance avelumab or best supportive care in a randomized phase-3 setting.
The reason we did the trial was because we felt the waiting until the cancer comes back in the second-line setting is too late. And we also felt that there were other aspects of the maintenance approach which may be attractive.
Essentially, the results of the trial showed that the patients who got avelumab compared to the patients who got best supportive care, from an overall survival perspective, had a significant overall survival advantage, with a hazard ratio of 0.69. The median overall survival in the avelumab arm was 21 months versus 14 months for best supportive care. When one looks at the PD-L1-positive population, that hazard ratio was 0.56. The PD-L1-positive population was a co-primary endpoint.
The benefit was across broad spectrums of patients, so it didn't matter which chemotherapy regime you got, or whether or not you had stable disease, or response to frontline treatment, or the presence or absence of visceral metastasis from a survival perspective. The benefit was across broad -- a broad spectrum of patients. And the progression-free survival also favored avelumab, again, with similar hazard ratios as seen with overall survival.
The drug was well tolerated, as you would expect, from a PD-L1 inhibitor. And it's in line with other PD-L1 inhibitors and other avelumab data in this setting. Therefore, in summary, this study, the JAVELIN-100 study, looking at maintenance avelumab sequenced with first-line chemotherapy, showed a significant survival advantage.
It's the first front-line randomized trial to show a survival advantage. The drug was well tolerated and worked across a broad spectrum of patients. And therefore, it could be considered a new standard of care in urothelial cancer.
Could you put these data in context of the recent study of maintenance pembrolizumab in the same setting?
And that publication came out in the JCO a few weeks ago, and Matt Galsky was the lead author. It was an investigator-initiated randomized phase-2 trial. And progression-free survival was the primary endpoint, and overall survival was a secondary endpoint. This had a similar progression-free survival, but did not hit overall survival.
It's not clear why there are differences between the two. Having said that, the randomized phase-3 was clearly powered for overall survival with 700 patients, where the randomized phase 2, which is smaller, was not powered for that. But both had a similar PFS signal. People will discuss different reasons why that might be the case, but comparing results across different studies has challenges, and that's a debate which I think we are going to have over the next few months.
What are the key unanswered questions?
Actually, when you look at the results of the maintenance approach in context, it looks like starting therapy before progression in the second-line setting-- this maintenance approach directly after chemotherapy-- is advantageous. So I think this will change the way we look at urothelial cancer. The really important questions now is firstly, is the chemotherapy-immune combinations going to also achieve a survival advantage? And we don't know that yet.
I think you do need to get a survival advantage to change practice. And so will the front-line chemotherapy-immune combinations achieve survival? That's an important next step because if they do, then the maintenance approach may become less relevant. However, if they don't achieve that survival advantage, it's possible or likely that actually, most of the benefit derived from those trials may be coming from, actually, the maintenance period, not the front-line combination period.
And again, that's the second really important debate the community needs to have. So debate number one-- around the pembrolizumab data. Debate number two-- around the atezolizumab- chemotherapy-combination data, and what that means, and what that's going to show in the future. We haven't yet seen the mature survival of that study or the pembrolizumab plus chemotherapy data. So that's the second really important step for me.
And then the third-important step is we haven't yet seen the biomarker-positive monotherapy mature data for pembrolizumab, atezolizumab, or atezolizumab, or, indeed, durvalumab, where we know the durvalumab data is negative. So the third-important question for me, in the short term, is what is the role of PD-L1 monotherapy in biomarker-positive chemotherapy-naive metastatic urothelial cancer?
So this data that we've presented here looks at a different approach. It is currently practice changing, in my opinion, and there are three key questions that will build on that, which we'll look at in the future.