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A Therapeutic Revolution: Immunotherapy for Bladder Cancer

Published: Friday, Mar 09, 2018



Transcript: 

Jonathan Rosenberg, MD: Treatment with immunotherapy dates back decades, actually, in bladder cancer. BCG (Bacillus Calmette-Guerin) was the first vaccine-based immunotherapy that was deployed in bladder cancer. It was deployed back in the 1970s. Long ago, it was FDA approved for non–muscle invasive bladder cancer. Until recently, it was the only therapeutic cancer vaccine that was used for treatment. It’s administered in the bladder, and it is actually quite effective at reducing the risk of relapse in patients who have resected non–muscle invasive bladder cancer. It also potentially may decrease the chance of relapse and progression in patients who have carcinoma in situ of the bladder—a noninvasive but aggressive cancer.

There really had been a therapeutic stagnation, for many years, without any improvements in non–muscle invasive bladder cancer treatment, or with immunotherapy, for advanced disease. Then, about 10 years ago, a trial was done in muscle-invasive bladder cancer that looked at the anti-CTLA–4 antibody, ipilimumab, as a single agent in pre-cystectomy patients. It showed that you could generate an immune response, leading to T-cell infiltration of immune cells into the tumor. That did not lead to further work at that time, but several years later, when the PD-1 and PD-L1 checkpoint antibodies entered the field, they were tested in metastatic bladder cancer. This led to the approval of 5 new drugs in the last 2 years to treat either newly diagnosed metastatic disease that has been untreated with chemotherapy or those who failed platinum chemotherapy.

And so, there has been a therapeutic revolution that’s happened in the treatment of bladder cancer—incorporating these agents, as single agents, into the treatment of advanced bladder cancer. Two drugs that were approved for first-line treatment of bladder cancer were pembrolizumab and atezolizumab. They were approved for patients who were ineligible to receive cisplatin. Cisplatin ineligibility is related to renal function, poor performance status, hearing loss, and inability to tolerate the fluid load of cisplatin. There are 3 other drugs that are approved for the second-line setting, but only in patients with prior platinum therapy. They are nivolumab, durvalumab, and avelumab. Both atezolizumab and pembrolizumab are approved in the second-line setting, as well.

There are multiple drugs that are being tested in combination with these agents, or independently, as immunotherapies for advanced urothelial cancer. And now they’re starting to move into the non–muscle invasive arena. Multiple trials are testing a single-agent checkpoint blockade or combinations of novel approaches with a checkpoint blockade in patients who have high-risk non–muscle invasive bladder cancer. Those trials haven’t read out yet. They’re currently ongoing and are actively accruing patients. These trials are industry sponsored trials and Cooperative Group trials.

Transcript Edited for Clarity 
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Transcript: 

Jonathan Rosenberg, MD: Treatment with immunotherapy dates back decades, actually, in bladder cancer. BCG (Bacillus Calmette-Guerin) was the first vaccine-based immunotherapy that was deployed in bladder cancer. It was deployed back in the 1970s. Long ago, it was FDA approved for non–muscle invasive bladder cancer. Until recently, it was the only therapeutic cancer vaccine that was used for treatment. It’s administered in the bladder, and it is actually quite effective at reducing the risk of relapse in patients who have resected non–muscle invasive bladder cancer. It also potentially may decrease the chance of relapse and progression in patients who have carcinoma in situ of the bladder—a noninvasive but aggressive cancer.

There really had been a therapeutic stagnation, for many years, without any improvements in non–muscle invasive bladder cancer treatment, or with immunotherapy, for advanced disease. Then, about 10 years ago, a trial was done in muscle-invasive bladder cancer that looked at the anti-CTLA–4 antibody, ipilimumab, as a single agent in pre-cystectomy patients. It showed that you could generate an immune response, leading to T-cell infiltration of immune cells into the tumor. That did not lead to further work at that time, but several years later, when the PD-1 and PD-L1 checkpoint antibodies entered the field, they were tested in metastatic bladder cancer. This led to the approval of 5 new drugs in the last 2 years to treat either newly diagnosed metastatic disease that has been untreated with chemotherapy or those who failed platinum chemotherapy.

And so, there has been a therapeutic revolution that’s happened in the treatment of bladder cancer—incorporating these agents, as single agents, into the treatment of advanced bladder cancer. Two drugs that were approved for first-line treatment of bladder cancer were pembrolizumab and atezolizumab. They were approved for patients who were ineligible to receive cisplatin. Cisplatin ineligibility is related to renal function, poor performance status, hearing loss, and inability to tolerate the fluid load of cisplatin. There are 3 other drugs that are approved for the second-line setting, but only in patients with prior platinum therapy. They are nivolumab, durvalumab, and avelumab. Both atezolizumab and pembrolizumab are approved in the second-line setting, as well.

There are multiple drugs that are being tested in combination with these agents, or independently, as immunotherapies for advanced urothelial cancer. And now they’re starting to move into the non–muscle invasive arena. Multiple trials are testing a single-agent checkpoint blockade or combinations of novel approaches with a checkpoint blockade in patients who have high-risk non–muscle invasive bladder cancer. Those trials haven’t read out yet. They’re currently ongoing and are actively accruing patients. These trials are industry sponsored trials and Cooperative Group trials.

Transcript Edited for Clarity 
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