We had the three updates from the JAVELIN Bladder 100 study at the virtual ASCO 2021 meeting. I will run through the three of them quickly. One of them was by Professor Powles and we look at different clinical and genomic subgroups of patients to evaluate whether the overall survival and progression free survival benefit with avelumab as switch maintenance therapy is consistent across different subsets of patients. For example, we look at the subset of patients with locally advanced unresectable disease versus metastatic disease with distant mets or based on the primary tumour location – upper or lower tract. We also looked at different molecular subsets – genomic findings or gene expression profiling findings. In this particular poster there was actually a poster discussion at ASCO which showed the benefit with avelumab switch maintenance therapy after response or stable disease to chemotherapy, platinum-based chemotherapy, seems to be consistent across the board across different clinical and molecular subsets of patients. There were some differences in the degree or magnitude of benefit but overall I would say that in the clinic the take home point from the practice in oncology is that we do not have an accurate molecular biomarker to select our patients and we offer avelumab for patients with response or stable disease after induction platinum-based chemotherapy if they have no progression.
The other abstract we presented and I was the first author in that poster, we calculated and measured the actual time from randomisation on the JAVELIN Bladder 100 trial until the end of next line therapy. We did not have granular data to answer the specific question of PFS2, PFS2 meaning the progression free survival of the second subsequent line of therapy, but to try to approximate or estimate the answer to this question we measured the time from the randomisation on the trial until the completion of the next line therapy. We saw that patients randomised to avelumab had a longer time from randomisation until the completion of the next line, the second line, therapy, thus corroborating the benefit with avelumab in a different angle, I would say. Obviously we would like to see particular impact of PFS2 but we did not have the granular data specifically for the duration of the second line therapy. But this is a relevant and reasonable approach in order to get data on how these patients do and how much time they spend in the first and second line therapy in advanced urothelial cancer, again supporting further the role of avelumab which has level 1 evidence in this first line setting of advanced urothelial cancer after response or stable disease to platinum-based chemotherapy.
The third abstract was a question about the treatment-free interval between the completion of first line chemotherapy, platinum-based chemotherapy, and the initiation of avelumab. In that clinical trial, the JAVELIN Bladder 100, we had a treatment-free interval of between 4 and 10 weeks and the question was does it matter? Is the benefit with avelumab in terms of overall survival and progression free survival dependent on how soon or late you start avelumab maintenance. We saw that the benefit appears to be across the board, regardless of the treatment-free interval, 4-6, 6-8 or 8-10 weeks between end of chemo and beginning of avelumab. This is important so it can inform discussions with the patients on when they start avelumab maintenance. However, in my clinical practice I’m worried about progression of disease, especially if we wait too long, and we know that median progression free survival is short, it can be as short as two months after the end of chemotherapy. So in my practice I tend to start earlier, sooner rather than later, so as long as the patient agrees, I discuss with the patient, of course, pros and cons based on social or family events. But I prefer and tend to start earlier, sooner rather than later, the avelumab maintenance.
Overall we keep working on the JAVELIN Bladder 100 programme and we are working on a manuscript of biomarkers and translational research and, of course, we keep evaluating data, quality of life, different subgroups so we can inform the scientific field and the community and keep identifying predictive biomarkers. So we are very excited about the work and hopefully we will see everybody in person when it’s safe, probably in the next year at the next ASCO meeting. Thank you so much for your attention.