Impact of Immunotherapy in Advanced Bladder Cancer
Insights From: Daniel J. George, MD, Duke University Medical Center
Daniel J. George, MD: Historically, bladder cancer has been one of the most difficult cancers to treat among the solid tumors in oncology for a long time. This is a patient population that’s pretty sick. Many of these patients are diagnosed later in life, in their 50s, 60s, and 80s even. These are patients who typically have a history of smoking and can have a number of other comorbidities, including cardiovascular issues, diabetes, or other medical concerns; pulmonary, asthma, and bronchitis issues. But the real problem has been the cancer.
In bladder cancer, up until very recently, all of our therapies have been based on platinum-based chemotherapy, particularly cisplatin-based chemotherapy, which is a difficult chemotherapy even in our healthy patients to tolerate. Many of our bladder cancer patients have just not been able to either tolerate it or just have been ineligible to get platinum-based chemotherapy. Even in those patients who are able to tolerate platinum-based chemotherapy, our response rates tend to be limited. They tend to be subtotal, and they tend to recur within 6 months of completing the chemotherapy. Following platinum-based chemotherapy, there really hasn’t been any therapy that has shown a reproducible, reliable, and durable treatment response. Most of our small phase II studies, and even limited phase III studies, in platinum-refractory patients hover around a 10% response rate. So, the majority of patients blasting through that, and median survivals following platinum-based chemotherapy, are dismal, 6 to 9 months, historically. So, this has been a tremendous unmet need in the field for decades now, until just recently.
Immunotherapy has been a real paradigm shift in oncology the past few years in a number of cancers. But there is perhaps no greater unfulfilled need than platinum-refractory bladder cancer. This has been the population of patients where we’ve really had nothing to offer these folks. They’re sick, they’ve had platinum chemotherapy. Many of them either didn’t respond to it or responded for a while but then progressed. Many of the patients are symptomatic still from their platinum-based chemotherapy with complications, including issues with neuropathies and nephritis. The reality is we had no therapies, until just recently, to offer these patients who have a reliable response rate or any real hope of a durable effect.
And then, immunotherapy comes into the field, particularly the checkpoint inhibitors, PD-L1 inhibitors and PD-1 inhibitors. And what we’ve seen over and over again is a reliable 20% to 30% response rate in these patients who historically had nothing available for them. And even more remarkable is the duration of these responses. These are just life-changing, hope-giving effects that I know we’ve seen in other cancers, but we’ve really seen nothing work in bladder cancer in this setting. And believe me, we’ve tried all kinds of classes of drugs. So, for immunotherapy to literally walk in to one of the most refractory settings of cancer, one of our most difficult patient populations, and to show a reproducible recurrent and durable treatment response is really nothing short of remarkable.