Insights From: Daniel J. George, MD, Duke University Medical Center
Daniel J. George, MD: Immunotherapy in bladder cancer is here to stay. There is no doubt about the fact that we have changed this platinum-refractory setting. There’s no doubt in my mind that this is going to become more and more a part of our frontline therapies, whether it’s in combination with chemotherapy or in sequence with chemotherapy. We’re going to see more and more patients receiving immunotherapy as monotherapy for bladder cancer. But I think what’s going to evolve in this field and what we’re excited about is the opportunity to use immunotherapy now perhaps in some novel settings to change the outcome. I think one of the real exciting opportunities is bladder-sparing approaches, so avoiding having to do a cystectomy and using chemotherapy, radiation therapy, and immunotherapy to help control this disease in situ and to create the immune recognition necessary to get cures and long-term complete responses in patients who have their tumor left intact, and consequently allow us to leave their bladder intact.
Most solid tumors now we’re doing organ-sparing approaches for esophageal, head and neck, many other GI settings, lung cancer, etc. This is a setting I think we need to revisit, and I think it’s something that’s going to happen. I think the other area that’s exciting for bladder cancer will be combination immunotherapies, and these are going to happen on the back end. These are going to happen, again, in platinum-refractory settings or even our checkpoint-refractory settings where we’re going to revisit immunotherapy perhaps in combination with some additional targets. To me, this may be more biomarker-driven in the future and understanding what in the immune system is really driving that immune escape and overcoming that. But I think in bladder cancer now that we’ve established PD-1, PD-L1 as a standard, that’s what we’ll be building off of in the future rather than cisplatinum-based regimens.
As exciting as this field is with where checkpoint inhibitors have taken us now, there’s a lot of work to be done. There’s still the 70% to 75% of patients who don’t respond to a PD-1, PD-L1 inhibitor, and we need to figure out how to get them responsive. We also need to understand how to get some of these partial responders to a more durable effect, we need to understand what to add to the checkpoint inhibitor, and we need to understand how to use these in earlier disease settings. There are some studies looking at checkpoint inhibitors in more superficial disease, but that may be risky. That certainly would be expensive, and it may be toxic in a subset of patients. So, understanding how to use other forms of immunotherapy or perhaps even localized immunotherapy in some of those settings will be key. Integrating immunotherapy around our standard surgery and radiation will be important, and then ultimately, recognizing when immunotherapy can stop. How long you have to treat patients with immunotherapy in this disease who are in a long-term remission will be another really important question. So, I think there’s a lot of questions to still get after.
There’s going to be more than immunotherapy for bladder cancer. There are genetic alterations that are actionable, targetable. Some of those are under active investigation now. Others will emerge. How to integrate precision medicine with immunotherapy to make both of those more effective will be another critical step in the new few years ahead. So, I’m excited about bladder cancer. It was hard to say that 5 years ago, but now we’re excited about bladder cancer and we’re excited to see where we can take this field. And we have something really positive to build off of. I think you’re going to see continued progress in this field for at least the next 5 to 10 years.