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Emerging Advances for Immunotherapy in Urothelial Cancer

Insights From: Jonathan Rosenberg, MD, Memorial Sloan Kettering Cancer Center
Published: Friday, Mar 09, 2018



Transcript: 

Jonathan Rosenberg, MD: These are very exciting times—in the treatment of advanced bladder cancer and even in non–muscle invasive bladder cancer. We have a whole new therapeutic armamentarium that we’re understanding how to better use in this disease. We are now understanding the role of combinations of these treatments with standard therapies, whether or not they augment chemotherapy or whether they detract from chemotherapy, which is also possible. In addition, the data from other tumor types is now being applied to bladder cancer, in terms of other novel combinations. I’m very excited about the new approaches with vaccine therapies, which generally appear to be very well tolerated and would be useful in this patient population. IDO inhibitors also represent a very promising therapeutic approach. Large randomized phase III trials have launched and are testing several of these.

One of the very interesting areas, right now, is in studying whether or not the same people who benefit from chemotherapy also benefit the most from immunotherapy. Patients with high levels of mutations often have DNA damage repair genes that sensitize them to both chemotherapy and, potentially, immunotherapy. There is the real possibility, in metastatic disease, that the combinations with the right cytotoxic chemotherapy or with immunotherapy might take a portion of patients who might do well with either agent alone and synergize and lead to cures in patients who have DNA damage repair mutations. And so, we think that there’s a possibility that there are certain patient populations for whom this terminal illness might no longer be terminal, if we apply the right treatments and understand the biology of the disease well enough.

We, and others, are conducting clinical trials with these combinations. Trials are analyzing the tumor genome, at the same time, to better understand which groups of patients will do extraordinarily well. At the same time, we need to remember that the majority of patients don’t have these mutations. We need to identify other approaches. There are other approaches, beyond immunotherapy, that are promising, at this time. There are classes of drugs, called antibody–-drug conjugates, which also look very promising. There is some evidence that some of these cell-killing mechanisms, with cytotoxics, leads to immunogenic cell death and may actually synergize with a checkpoint inhibitor. And so, beyond immunotherapy, there are multiple approaches that are being tested. Many of these look very promising.

Transcript Edited for Clarity 
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Transcript: 

Jonathan Rosenberg, MD: These are very exciting times—in the treatment of advanced bladder cancer and even in non–muscle invasive bladder cancer. We have a whole new therapeutic armamentarium that we’re understanding how to better use in this disease. We are now understanding the role of combinations of these treatments with standard therapies, whether or not they augment chemotherapy or whether they detract from chemotherapy, which is also possible. In addition, the data from other tumor types is now being applied to bladder cancer, in terms of other novel combinations. I’m very excited about the new approaches with vaccine therapies, which generally appear to be very well tolerated and would be useful in this patient population. IDO inhibitors also represent a very promising therapeutic approach. Large randomized phase III trials have launched and are testing several of these.

One of the very interesting areas, right now, is in studying whether or not the same people who benefit from chemotherapy also benefit the most from immunotherapy. Patients with high levels of mutations often have DNA damage repair genes that sensitize them to both chemotherapy and, potentially, immunotherapy. There is the real possibility, in metastatic disease, that the combinations with the right cytotoxic chemotherapy or with immunotherapy might take a portion of patients who might do well with either agent alone and synergize and lead to cures in patients who have DNA damage repair mutations. And so, we think that there’s a possibility that there are certain patient populations for whom this terminal illness might no longer be terminal, if we apply the right treatments and understand the biology of the disease well enough.

We, and others, are conducting clinical trials with these combinations. Trials are analyzing the tumor genome, at the same time, to better understand which groups of patients will do extraordinarily well. At the same time, we need to remember that the majority of patients don’t have these mutations. We need to identify other approaches. There are other approaches, beyond immunotherapy, that are promising, at this time. There are classes of drugs, called antibody–-drug conjugates, which also look very promising. There is some evidence that some of these cell-killing mechanisms, with cytotoxics, leads to immunogenic cell death and may actually synergize with a checkpoint inhibitor. And so, beyond immunotherapy, there are multiple approaches that are being tested. Many of these look very promising.

Transcript Edited for Clarity 
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