The Future of Immunotherapy in Bladder Cancer

The treatment of bladder cancer is moving away from VEGF-targeted therapies toward immune checkpoint inhibition, according to Dr. Thomas Powles, director of Barts Cancer Centre in London.

In an interview with CURE® during the American Society of Clinical Oncology’s 2020 Genitourinary Cancers Symposium, he discussed the future of treatment for the disease and what it means for patients.

CURE®: How is the field of treating bladder cancer transforming?

Powles: There are two really big findings in urothelial cancer at the moment. There are two randomized phase 3 (trials). We don’t have the data yet, but the press release tells us that the maintenance approach with immune therapy after chemotherapy — so metastatic disease, induction chemotherapy, and then maintenance avelumab (Bavencio) versus best supportive care — is showing a survival advantage. So that is the first frontline trial with a survival advantage.

There are two key learnings. Number one, it’s not necessarily the case that combining things improves outcomes yet. But we do know the maintenance period does appear to be important. Observation two is just copying what we do in lung cancer but it’s probably not the best way of approaching these cancers. I talked previously about neoadjuvant chemotherapy and the biology we learned from the disease, which is important, and we will need to treat it differently in the future.

What does the latest CheckMate 214 data mean for patients?

The 42-month follow-up of the CheckMate 214 data is really important because it shows long-term durable remissions. This is important because there was always the fear that immune checkpoint inhibitors would open a new chapter but the durability that we saw initially would not be sustained. And sometimes patients can relapse, three or four years down the line, but if that was to occur what we would have achieved was a very provocative signal. But how many patients five years down the line are still alive?

Many of our endpoints are quite early, 12-month survival or two-year survival. But when you speak with patients, they’re looking for more than 12-month survival. All patients want to see not next Christmas but Christmas in five- and 10-years’ time. This data is pointing toward that, that we can actually change the biology of the disease not just sort of altering the deck chairs on the Titanic but keeping the Titanic afloat.

What lies ahead for bladder cancer?

Looking into the future there is a study called COSMIC-313 and the control arm is ipilimumab (Yervoy)/nivolumab (Opdivo). Many people have done a lot of work in the development of VEGF-targeted therapies and it’s been really successful, but I think we’ve moved on from VEGF-targeted therapies in frontline renal cancer. I think we have now moved to a backbone of immune checkpoint inhibition. I hope (COSMIC-313) is going to be positive because it’s bringing everything together and making sure that there aren’t any patients who aren’t getting the three active targets that we know are really important in this disease.