The second abstract that I would like to talk to you about is the updates that we provided from the JAVELIN Bladder 100 trial. Just to remind the audience, this was a practice-changing phase III trial that was presented by Professor Powles at the virtual ASCO 2020 at the plenary session, and it was published by the "New England Journal of Medicine" in September 2020.

Very briefly, the design of the JAVELIN Bladder 100 trial. This is a trial, phase III, that enrolled patients who had completed platinum-based chemotherapy, gem/cis or gem/carbo, as first-line induction chemotherapy in patients with metastatic urothelial cancer.

These patients had completed gem/cis or gem/carbo and had achieved a response or stable disease in the first-line setting, and patients were randomized to avelumab and the PD-L1 plus best supportive care or best supportive care alone, one-to-one randomization with the primary endpoint of overall survival.

Patients were stratified based on the site of metastasis, visceral or non-visceral, and also a response to induction chemotherapy. This trial saw the significant clinical and statistical significance, overall survival, and progression-free survival benefit with avelumab as switch maintenance therapy in patients who had achieved response or stable disease to induction chemotherapy.

In our new ASCO 2021 update, we looked at different questions. For example, I presented an abstract looking specifically at the time interval between randomization of the JAVELIN trial and the completion of the second-line therapy, so the next-line therapy after progression on the maintenance phase.

We did this in order to, let's say, approach the answer to the question, does avelumab maintenance have an impact in the subsequent line of therapy? It was very difficult to granularly get data about second-line therapy, specifically the dates.

We could not evaluate specifically the PFS2, the progression-free survival on the second-line therapy, but we tried to, as I mentioned, measure the time interval from randomization of the JAVELIN Bladder 100 maintenance trial and end of next-line therapy.

We saw that avelumab maintenance significantly prolongs the time interval between randomization and end of next-line therapy, overall corroborating the important role and the level-one evidence that we have shown with avelumab as switch maintenance therapy in patients with response or stable disease or induction-based chemotherapy.

There were a couple of other posters that were presented by Professor Powles and Dr. Schroeder. The bottom line of those posters was that the benefit with avelumab as switch maintenance therapy in the first-line setting of advanced urothelial cancer was across the board and was notable across the board regardless of which subset of patients you look at.

For example, patients with locally advanced unresectable disease versus distant metastasis, patients with lymph node-only disease or visceral, patients who got carbo/gem followed by avelumab maintenance versus best supportive care.

The benefit appears to be across the board regardless of the subset of patients of how you look at them. Also, despite the very interesting biomarker work we did in the JAVELIN Bladder 100 trial, there is no clinically useful molecular biomarker.

We do not use PD-L1, TMB, or molecular subtype to select patients. In my practice, if a patient has a response or stable disease to induction platinum-based chemotherapy in the first-line setting, I offer this patient avelumab switch maintenance as long as there is no contraindication to immunotherapy.

As long as there is no significant contradiction, patients should be offered avelumab if they are fit for immunotherapy in this maintenance setting. The last point to make is we also looked at the treatment-free interval between the completion of chemotherapy and the initiation of avelumab maintenance.

Does a treatment-free interval matter in that JAVELIN Bladder 100 trial? There was a treatment-free interval between 4 and 10 weeks, and we looked at the different subset of patients, 4 to 6, 6 to 8, 8 to 10 weeks. Did that impact the benefit of maintenance avelumab therapy?

The answer was that the benefit was across the board in different subsets of patients regardless of the treatment-free interval. Patients had benefit. However, in my practice, I discuss with my patients, and I prefer to start avelumab maintenance sooner than later.

Those patients had a very short median progression-free survival after response or stable disease to chemotherapy, and I am worried about losing patients because of progression. I discuss with the patients, and if the patients agree, I tend to start avelumab maintenance sooner than later, earlier than later, just to avoid them entering progression and attrition.

After we presented by Dr. Schroeder, the benefit appears to be regardless of treatment-free interval. Overall, I think the data corroborated and reinforced the level-one evidence with avelumab as switch maintenance therapy in the first-line setting.

This trial was a global effort. We had it open at the Seattle Cancer Care Alliance, University of Washington, and Fred Hutchinson. It was, as I mentioned, a global effort with 700 patients accrued. Big thanks to the patients and families.

The co-investigators and of course collaborators and staff from multiple sites around the world were working in the JAVELIN Bladder 100 Program to further inform practical questions, and obviously, we want to look at more biomarkers. We also showed some interesting quality-of-life, patient-reported outcomes data.

I would like to thank you for the attention and looking forward to seeing you face-to-face when it is safe, probably next year. In the meantime, stay safe and well. Thanks again.