The FDA recently approved avelumab (Bavencio®, EMD Serono, Inc.) for patients with advanced urothelial carcinoma (UC). Thomas Powles, MBBS, MRCP, MD, discusses with i3 Health the implication of this approval and future steps for research and offers community oncologists advice on treating this patient population.
What are the most challenging aspects of treating patients with locally advanced or metastatic UC?
Thomas Powles, MBBS, MRCP, MD: The overall survival outcomes are poor for the disease. Treatment for UC has not been particularly curable.
Can you comment on the significance of the FDA approval of avelumab for UC?
Dr. Powles: For first-line metastatic disease, current treatment is based around chemotherapy, and when that chemotherapy fails, second-line therapy is based around immune checkpoint inhibitors, such as pembrolizumab and atezolizumab. The problem with chemotherapy is that it has a high response rate, but the cancer invariably comes back quickly. And the problem with second-line immune checkpoint inhibitors is that most patients can't receive it because many patients are too ill to have second-line therapy. And those that do get the immune checkpoint inhibitors, if it is not given enough time, it won't achieve control of the disease. So the avelumab study brings forward the immune checkpoint inhibitor and sequences it directly off the chemotherapy. And by doing that, you get initial control with the chemotherapy, and then you maintain that control with the immune checkpoint inhibitor. And you don't run the risk of waiting for cancer to come back in many cases, which will be too late.
Dr. Powles: The results of the research are that if you give the immune checkpoint, but directly after chemotherapy, you improve survival by 31% and you delay progression-free survival by similar amounts. It works in many subgroups of patients, irrespective of what chemotherapy they've had before, their response to previous chemotherapy, and whether or not they're biomarker positive. Avelumab is well tolerated, and most patients who progress on the control arm, ended up getting subsequent chemotherapy. So it really does suggest that if you give the drug earlier, it results in a survival advantage. The implications of the research are that it will become a new standard of care instead of waiting until the cancer returns. Sequencing avelumab directly off chemotherapy appears to be a new side of the care. And as you're aware, the FDA recently approved that.
How do you see the treatment landscape evolving in the coming years?
Dr. Powles: Well, I think that this step is important because it doesn't look like the combination of chemotherapy plus immunotherapy will result in a viable advantage in my opinion. We therefore think that actually it may be better to sequence these drugs than giving them concurrently. So it looks like sequencing will be an important step for the future of bladder cancer, specifically immunotherapy and chemotherapy.
Do you have any advice for community oncologists who treat this patient population?
Dr. Powles: I think the important thing in metastatic urothelial cancer is that frontline immunotherapy is not great at getting control of disease, whereas frontline chemotherapy is very good at getting control of the disease. Because of that reason, it's easier and safer and probably better for patients to get frontline chemotherapy, getting control of the disease with that, and then give maintenance immunotherapy rather than the other way around—giving immunotherapy first and then try the sequencing in the chemotherapy. So I would say to community oncologists that giving chemotherapy first is probably the easiest way in getting in control of the disease. And, I think that this is important in urothelial cancer because remember, survival of these patients remains very short.
About Dr. Powles
Thomas Powles, MBBS, MRCP, MD, is a Professor of Genitourinary Oncology and a Director at Barts Cancer Center. His research interests include genital and urinary cancers, and he leads a spectrum of clinical studies from phase 1 to randomized phase 3. The majority of these studies are translational phase 2 studies investigating novel targeted and immunotherapies.
For More Information
Bavencio® (avelumab) prescribing information (2020). EMD Serono. Available at: https://www.bavencio.com/
Powles T, Grivas P, Aragon-Ching JB, et al (2016). A multicenter, international, randomized, open-label phase 3 trial of avelumab + best supportive care (BSC) vs BSC alone as maintenance therapy after first-line platinum-based chemotherapy in patients with advanced urothelial cancer (JAVELIN Bladder 100). Annal of Oncol, 27(6):266-295. Abstract 596. DOI:10.1093/annonc/mdw373
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.