Early Trial Data Provide Reason for Hope in Bladder Cancer

Though bladder cancer remains difficult to treat, there is reason for some hope.

An analysis of the immunotherapy durvalumab to treat approximately 60 patients with urothelial bladder cancer were “impressive,” according to Saeed Rafii, but major questions remain. Rafii presented on the study at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO), a gathering of 30,000 oncology professionals in Chicago.

CURE discussed these trial results with Rafii, a researcher at the Sarah Cannon Research Institute in London, and looked to gain insight into the future of bladder cancer care.

Can you give an overview of this study and its findings?

The study was a large phase 1 clinical trial of durvalumab in solid tumor cancers. More than 1,000 patients with 15 different tumor types participated in this clinical trial, but we presented data on about 61 patients with urothelial bladder cancer.

What are the next steps following this study?

Tecentriq (atezolizumab) was recently approved by the FDA for bladder cancer. Would it be worth comparing Tecentriq and durvalumab in a trial?

The most significant finding from this study was the impressive overall response rate to durvalumab in urothelial bladder cancer, which is a significant considering that the response rate to chemotherapy is quite low. Additionally, in the past 20 years, there have been few advances in the treatment of bladder cancer. The next step is to find out whether immunotherapies are going to do better than chemotherapy. Of course, we need to find out biomarkers for response to treatment. We also need to find out whether there’s going to be any improvement in overall survival rate in combination with other agents, such as anti-CTLA-4 inhibitors or other targeted therapy agents.We have a lot of other questions to answer first. I think we need to find out if there are other biomarkers of response to the treatment other than PD-L1 expression. Secondly, we need to find out how this agent in combination with other agents compares with chemotherapy and whether we need to bring it forward — before disease is metastatic — and try it in the adjuvant setting. There might be a trial comparing Tecentriq and durvalumab, but it won’t be any time soon.

What are some of the biggest challenges in treating patients with bladder cancer?

We need to be mindful of adverse events. We know that some of these agents cause nephritis, so we have to be careful about that, although the rate of toxicities relating to agents are not really high in durvalumab. Only one patient had a grade 3, drug-related, acute kidney injury, which was reversible. In terms of treatment-related adverse events, I think this treatment, generally speaking, was very well-tolerated so we just need to make sure we’re selecting the right patients.

What do you think treatment of bladder cancer will look like five years from now?

In the coming years, we’ll have trials with immunotherapies in bladder cancer and with immunotherapy combinations. I know there are a couple of basket trials at the moment trying to look at different combinations with Lynparza (olaparib), and maybe FGFR inhibitors in bladder cancer. There is trial going on now looking at Opdivo (nivolumab) in comparison with chemotherapy. In the next few years, we’ll hear more about immunotherapies and whether they’ll be combined with chemotherapy, used as single agents or combined with targeted agents.