Thomas Powles, MD, PhD on Next Steps for Avelumab and the Future of Treatment for Urothelial Cancer

Interim analysis from the phase III JAVELIN Bladder 100 trial suggest avelumab (Bavencio) as first-line maintenance in patients with urothelial cancer whose disease has not progressed with platinum-based chemotherapy should become the new standard or care, according to a late breaking abstract presentation at the 2020 ASCO Virtual Scientific Program.

In an interview with CancerNetwork, lead study author Thomas Powles, MD, PhD, director of Barts Cancer Centre, London, UK talked about future directions for avelumab research and treatment options for patients with advanced urothelial cancer as a whole.

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So, there are two parts to that question. The first is are there next steps for the avelumab (Bavencio) program, and are there next steps for urothelial cancer more widely. And I think I'm going to answer the second question first, urothelial cancer is moving incredibly quickly. If you go back 5 years, we use chemotherapy and when that failed, outcomes of patients was poor. Subsequent to that in the United States, we've introduced immune therapy. We've also introduced targeted therapy with fibroblast growth factor (FGF) inhibitors in the form of erdafitinib (Balversa). And we also have antibody drug conjugates with enfortumab vedotin (Padcev). That is three major changes over a very short period of time now changing the frontline treatment plans. We've changed it already with immunotherapy and biomarker-positive patients with atezolizumab (Tecentriq) and pembrolizumab (Keytruda) and we're now changing frontline immune therapy by sequencing chemotherapy and immunotherapy. So, we've done quite a lot in this period of time, but the next steps are really important. We need to improve our biomarker work and we need to do more combination work. At the moment we haven't been successful with combinations. As it currently stands, the immune targeted combinations, and the immune chemotherapy combinations have not yet made the big impact we expect. And importantly, the immune/immune combinations haven't made that change either. I think, my personal opinion, is we will see progress in those groups over the next 12 months. And I'm particularly excited about the immune/immune combinations. I also think we need to move the drugs earlier in the non-muscle invasive disease and the muscle-invasive disease space. We already have some preliminary data in that space, which is encouraging. And I think that's how you end up curing more patients. And then the final piece of this is about personalized therapy and selecting patients. We're beginning to understand a lot more about urothelial cancer than we did five years ago. And there is actually some data at ASCO this year with atezolizumab, looking at subsets of patients with two biomarkers, high mutational burden and high PDL-1, doing exceptionally well with immunotherapy. And so, the answer to your question, the first part is there is a huge amount of next steps and work to do. And this is only one piece in that jigsaw. In terms of what we need to do with avelumab, I think we need to clarify a few things. Number 1 is it would be useful to look at the quality of life data and the biomarker data in this study. Number 2 is moving forward, it will be nice to do further studies with avelumab. There aren't other randomized phase III [studies] currently with this particular drug, and I think we should be doing those. And we should be also in my opinion, refining the issue around maintenance therapies. Questions like how many cycles of chemotherapy do you really need to give? And can we sequence the drugs different? And, then can we sequence them in the perioperative space as well?