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Frontline Immunotherapy in Advanced Bladder Cancer

Insights From: Daniel J. George, MD, Duke University Medical Center
Published: Friday, Jan 05, 2018



Transcript: 

Daniel J. George, MD: For our patients who are, say, cisplatin-ineligible but maybe aren’t quite as symptomatic, maybe then I’m more concerned about their long-term tolerance to chemotherapy. I’m worried about maybe some other complications associated with chemotherapy. Say, perhaps they’re a little bit frail, I’m worried about GI tolerance with diarrhea, nausea, vomiting, weight loss, etc. Immunotherapy is an attractive approach. For many of these patients, immunotherapy may be the only therapy that they can tolerate, and what’s nice about this is we have a couple of immunotherapy options.

Pembrolizumab and atezolizumab have both been shown to have activity in this space. Pembrolizumab has shown a response rate that is quite impressive, about 30% response rate in this setting. That, to me, is very attractive. And given the fact that in the platinum-refractory setting it also is associated with a survival benefit, really, to me, makes it a standard choice in this setting. Atezolizumab is a very reasonable alternative, however. It also has activity in cisplatin-ineligible, as well as in platinum-refectory populations. It’s also an every-3-week administration. We don’t have any head-to-head data comparing these 2, so we can’t really say if one is better than the other.

To me, I think we have 2 good options. I’m comfortable with either choice. Some of that may depend on the comfort level of the physician in their practice with each of these agents. But it’s nice to know that we’ve got these 2 options. At this point in time, it’s hard to say that there are benefits to one or the other mechanistically, but they are different. One is targeting PD-L1, one is targeting PD-1. It’s possible there might be slightly different side effect profiles. One area that’s of interest in particular would be issues around PD-L2 toxicities, which you might see more by blocking PD-1 without necessarily see with blocking PD-L1. So, that’s something to look for in the future. I don’t know that we’ve fully defined that, but mechanistically, that’s where these 2 agents differ. It might be something then in the future we see as a marker for who we might choose one approach over the other.

Pembrolizumab has really defined now the standard for checkpoint inhibitors in bladder cancer, particularly now that it’s demonstrated a survival benefit in the platinum-refractory setting. More recently now, we’ve seen the data with KEYNOTE-052, which is a frontline study in patients with cisplatin-ineligible transitional cell carcinoma bladder cancer. And in that population, we see about a 30% response rate associated with pembrolizumab. This is, I think, very exciting for this patient population that historically has tolerated therapies rather poorly and has seen very few durable responses associated with this therapy. In the KEYNOTE-052 study, there were 6% complete response rates. That’s really remarkable for that patient population, again with very few treatment options. It’s become, for us, a standard of care for many of our patients who we deemed ineligible for platinum chemotherapy.

Transcript Edited for Clarity 
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Transcript: 

Daniel J. George, MD: For our patients who are, say, cisplatin-ineligible but maybe aren’t quite as symptomatic, maybe then I’m more concerned about their long-term tolerance to chemotherapy. I’m worried about maybe some other complications associated with chemotherapy. Say, perhaps they’re a little bit frail, I’m worried about GI tolerance with diarrhea, nausea, vomiting, weight loss, etc. Immunotherapy is an attractive approach. For many of these patients, immunotherapy may be the only therapy that they can tolerate, and what’s nice about this is we have a couple of immunotherapy options.

Pembrolizumab and atezolizumab have both been shown to have activity in this space. Pembrolizumab has shown a response rate that is quite impressive, about 30% response rate in this setting. That, to me, is very attractive. And given the fact that in the platinum-refractory setting it also is associated with a survival benefit, really, to me, makes it a standard choice in this setting. Atezolizumab is a very reasonable alternative, however. It also has activity in cisplatin-ineligible, as well as in platinum-refectory populations. It’s also an every-3-week administration. We don’t have any head-to-head data comparing these 2, so we can’t really say if one is better than the other.

To me, I think we have 2 good options. I’m comfortable with either choice. Some of that may depend on the comfort level of the physician in their practice with each of these agents. But it’s nice to know that we’ve got these 2 options. At this point in time, it’s hard to say that there are benefits to one or the other mechanistically, but they are different. One is targeting PD-L1, one is targeting PD-1. It’s possible there might be slightly different side effect profiles. One area that’s of interest in particular would be issues around PD-L2 toxicities, which you might see more by blocking PD-1 without necessarily see with blocking PD-L1. So, that’s something to look for in the future. I don’t know that we’ve fully defined that, but mechanistically, that’s where these 2 agents differ. It might be something then in the future we see as a marker for who we might choose one approach over the other.

Pembrolizumab has really defined now the standard for checkpoint inhibitors in bladder cancer, particularly now that it’s demonstrated a survival benefit in the platinum-refractory setting. More recently now, we’ve seen the data with KEYNOTE-052, which is a frontline study in patients with cisplatin-ineligible transitional cell carcinoma bladder cancer. And in that population, we see about a 30% response rate associated with pembrolizumab. This is, I think, very exciting for this patient population that historically has tolerated therapies rather poorly and has seen very few durable responses associated with this therapy. In the KEYNOTE-052 study, there were 6% complete response rates. That’s really remarkable for that patient population, again with very few treatment options. It’s become, for us, a standard of care for many of our patients who we deemed ineligible for platinum chemotherapy.

Transcript Edited for Clarity 
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