Video
EV+P Combination Strategy Changing Bladder Cancer Treatment Landscape
Enfortumab vedotin monotherapy or its combination with pembrolizumab could significantly evolve the treatment landscape for urothelial cancer.
Arlene Siefker-Radtke, MD: Looking at the data presented, it’s certainly very possible that enfortumab vedotin [EV] plus pembrolizumab could be a game-changer in how we treat our patients with metastatic urothelial cancer. The combination is showing an improved objective response rate. It’s also suggesting an improvement in the median duration of response that we hope will translate to the overall survival benefit that we all hope to achieve when developing combination strategies. With a response rate this high, there’s even thought [about whether] this could compete with cisplatin-based chemotherapy. Even though [chemotherapy] is given in less than half of patients with metastatic urothelial cancer, itstill has toxicity, with neutropenic fever rates around 30% or greater, often resulting in readmission to the hospital.
When we develop a combination that has an improved toxicity profile, it may allow patients to remain on that therapy much longer than they would for any alternate therapy. If we improve toxicity, [we’ll see] fewer readmissions to the hospital, and an improved physical condition should they eventually need subsequent chemotherapy or treatment.
We’re all looking forward to the large phase 3 randomized trial comparing EV and pembrolizumab with EV alone in patients with frontline metastatic urothelial cancer. If these very promising early data pan out in the frontline setting with that larger phase 3 trial, we’ll have a new standard for our cisplatin-ineligible patients. Depending on the clinical activity that’s observed, we may even have a strategy that can finally take on cisplatin as a new way of treating our patients with bladder cancer.
I’m often asked how this combination may impact potential treatment approaches. We have a frontline strategy of chemotherapy followed by maintenance avelumab. If we have a better, less toxic frontline agent, it may result in more patients getting to the immune checkpoint inhibitor. It may also help enhance immune response when combining it with an immune checkpoint inhibitor. It’s possible that antigen release may result in improved enhancement of the immune response. It’s also possible that sheer cytoreduction of tumor volume can impact how well our immune system can respond or help control cancer.
When you look at the single-agent immunotherapy data and the treatment of patients with bulky [disease] and high disease burden, it often feels like we’re trying to put out a 3-alarm fire with only 1 fire truck when we’re giving an immune checkpoint inhibitor alone. The ability to cytoreduce, to get those tumors to a smaller size, may allow us more time to give the patient that immune checkpoint inhibitor, enhance the immunogenicity against the tumor, improve the objective response rate, and ultimately contribute to that enhancement in overall survival. That’s what we’re seeing based on the preliminary data from this ESMO [European Society for Medical Oncology Congress] abstract with that enhancement of response when combining enfortumab vedotin with pembrolizumab. We’re hoping that improved durability of response will translate to a significant overall survival benefit for our patients with bladder cancer.
When thinking about clinical outcomes for patients with bladder cancer in general, historically, we have focused on objective response rate as an early signal of potential clinical activity. Certainly, most clinical trials have first needed to show an improved objective response rate before we saw that translation to survival benefit. But not every strategy or chemotherapy agent that has been developed has a response rate that’s as promising. Even some with promising response rates haven’t had as much survival benefit as one would hope. As a result, we look at other criteria as well. Durability of response appears to be one of those promising signs. If you get not only a good response but a response that’s durable, then you have a combination or a treatment that has that potential to improve overall survival, resulting in FDA approval of that therapy.
Transcript edited for clarity.
