One of the main challenges with checkpoint inhibitors is that they do not work for everyone. There is a lot of excitement because when they do work, they work well. The fact remains that 70% to 80% of our patients do not respond to them and will not achieve benefit. What we are now looking at in clinical trials are ways to improve the activity of immunotherapy. For example, novel agents in combination with these checkpoint inhibitors, such as IDO inhibitors, are on the forefront of investigation. These are agents that are not immunotherapeutic for patients who either cannot tolerate immunotherapy or quickly progressed through them.
Are there any combinations that are looking promising?
In terms of checkpoint combinations, there are a couple of trials that are in development. One is with an IDO inhibitor epacadostat with pembrolizumab. There is also an IDO inhibitor in combination with nivolumab being tested by Bristol-Myers Squibb. The early phase I data with epacadostat and pembrolizumab was encouraging in terms of efficacy in patients with previously treated bladder cancer. That will be explored going forward.
Another combination is ipilimumab (Yervoy) and nivolumab. Again, we have seen the phase I basket data for that combination but based on the efficacy and the durability of response in those patients, it has been investigated in a phase III trial, as well. There are immunotherapy combinations, immunotherapy novel combinations and immunotherapy chemotherapy combinations, which all need to be investigated further. Hopefully, we will be smarter about them this time next year. Looking back on this year, how would you describe the growth of immunotherapy in bladder cancer?
The last approval prior to May 2016 in bladder cancer was cisplatin in 1978. It has been a long drought in bladder cancer, but now there is an explosion of approvals and interest in bladder cancer. There are more trials for patients with bladder cancer than ever before, which is wonderful for our patients and the community of us who treat bladder cancer. This was a huge year for publications and for many of these early data that we saw in meetings in 2016.
Again, we are going to be seeing a lot of new data at upcoming meetings that are going to advance the field forward. The standard of care today might not be the standard for very long.
Is there anything else you would like to add?
Helping clinicians choose therapies in the metastatic space is important because it is more confusing now for good reasons. There are good clinical trials available now with agents that have demonstrated efficacy in early phase trials and early phase designs involving rational testing of novel biologic agents. It has never been a better time to consider a clinical trial.
Smith DC, Gajewski T, Hamid O, et al. Epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma: Preliminary phase I/II results of ECHO-202/KEYNOTE-037. J Clin Oncol. 35 2017 (suppl; abstr 4503).