Alicia Morgans: Hi, I'm so excited to be at ASCO 2022 with Dr. Cora Sternberg, where we're talking about the latest and greatest on the JAVELIN trial. So thank you so much for speaking with me today, Dr. Sternberg.

Cora Sternberg: It's a pleasure to be here as always. Thank you, Alicia.

Alicia Morgans: Well, thank you. And you know, you were a participant in this JAVELIN Bladder 100 trial and have been one of the presenters in various settings for the data that continues to come out of this study. And data's been presented at multiple meetings over the last number of months.

Cora Sternberg: That's true.

Alicia Morgans: Really continues to be so exciting. So can you set the stage for us? Let us know, remind us, what was the JAVELIN Bladder 100 trial?

Cora Sternberg: So the JAVELIN Bladder 100 trial was for patients with urothelial cancer that was either metastatic or locally advanced, inoperable cancer, that were treated with platinum-based combination therapy, either cisplatin or carboplatin and gemcitabine, treated between four and six cycles. And those patients, we chose the patients who either had a complete response, a partial response, or stable disease. We did not have any patients who progressed on chemotherapy. There were 700 patients in that trial. We then waited about four to 10 weeks and those patients were then randomized between receiving Avelumab, which is a PD-L1 inhibitor, IV every two weeks or observation. And what we saw was clearly that the patients who received Avelumab, we didn't wait until they progressed, as we've had immunotherapy, second-line therapy. This is called switch maintenance. But by treating patients before they progressed and switching over immediately to the Avelumab, that the overall survival was prolonged compared to not receiving treatment.

And this has made it into all of the guidelines, NCCN, ESMO, AUA, and has become actually a real standard of care to do the switch maintenance and not wait for patients to progress and then get a second line of immunotherapy. We've looked at lots of different things in this trial. We've looked at the patients who had CR and PR and stable disease. All of those patients benefit. We look at all patients as compared to the PD-L1 positive patients. I would say the PD-L1 positive patients benefited a little bit more, but everyone actually benefited. We've looked at the patients who had four, five or six cycles of chemotherapy and perhaps it's better to give six cycles, but actually, even if they've only had four cycles, or five, or six, they all benefit. Actually, all subgroups of patients benefited, those who got carboplatin, those who got cisplatin, all benefited by getting the switch maintenance to Avelumab.

Alicia Morgans: So let's dig in a little bit to some of these subgroup analyses that you just mentioned, because I think they're so relevant in clinic. Let's start with the one that I think you actually presented, which was four versus five or six cycles of chemotherapy. And then understanding whether the number of cycles of chemotherapy was associated with outcome in clinical practice. This is really relevant because we certainly see patients that we can't get all the way through cycles even if that's our original plan. Does this come into play in your practice?

Cora Sternberg: It does come into play into my practice and I try to give six cycles of chemotherapy and I try to give cisplatin chemotherapy when I can and not carboplatin chemotherapy. And in this trial, those patients who had four or five cycles benefited, not quite as much as those who had six cycles, but they did benefit. They had a really important benefit. When we were first designing the trial, I tried very hard to get MVAC into the trial and not just have gemcitabine and carboplatin or platinum. I was initially one of the first principal investigators of this trial, but people didn't want to confuse the waters. But if you look at the guidelines, the guidelines now say that it should be used with either gemcitabine and a platinum or dose-dense MVAC, which really wasn't evaluated in this trial.

But I think that what we can say is that anyone who's had combination chemotherapy with a platinum, be it MVAC or Dose-dense MVAC, or gemcitabine carbo, or cisplatin, and have responded with a CR, a PR, or stable disease, are eligible. I think many people are more willing to try to give upfront, even gem carboplatin, where they may not have been before, to try to give at least four cycles of that and to then switch over for those patients that they're not really sure about whether or not they should give chemotherapy, knowing that they can maybe get away with giving four cycles and still have a benefit. I do try to give cisplatin and I do try to give six cycles when possible.

Alicia Morgans: And I think so many of us do, but to your point, we can't always do it. We don't always achieve that goal, but it is so helpful to know that these patients can still respond. And then other data that was presented at ASCO 2022 was really around stable disease, CR, PR, all of these patients seemed to really benefit. You didn't have to have a PR or a CR to receive some benefit from this treatment.

Cora Sternberg: Exactly, exactly. And we saw that the patients on the placebo arm, many, many more got second-line therapy than those who were on the Avelumab arm, because they just stayed on Avelumab for a very long time, so not as many got second-line therapy

Alicia Morgans: And important too that we had a control arm where patients did receive subsequent therapy, so it was a bit of a fair comparison against this early initiation of Avelumab.

Cora Sternberg: But you know, the first data were presented with a follow-up in October. It was October 21st, 2019. And now we have more than 38 months of follow-up until June 2021. So as the follow-up increases, the data got even a little bit stronger in terms of the overall survival benefit in this study, so I think that's important too that we have much longer follow-up.

Alicia Morgans: I agree. And really, I think this data changed practice, changed standard of care for any patient who can get a platinum combination. So gem or gem with cisplatin or carboplatin, has stable disease or better, really we need to offer our patients maintenance Avelumab. There's a seven-month survival benefit. This holds even at a longer-term follow up, and as long as our patients get a stable disease or better, they really can hopefully benefit from this treatment. Thank you so much for your time and your expertise today.

Cora Sternberg: My pleasure. Thank you.