Practical Considerations With Checkpoint Inhibitors in Bladder Cancer
Insights From: Daniel J. George, MD, Duke University Medical Center
Daniel J. George, MD: Checkpoint inhibitors in bladder cancer have been remarkable on the efficacy side, but there are still concerns about safety in this patient population. And it has to do with both the disease and the patient population. With the disease, particularly when I have patients who have visceral disease or bone metastases, these are the patients who get medical complications very quickly. And so, this is the group of patients where I like to monitor them very frequently. With a lot of checkpoint inhibitors, after a while, we’ll see them every other visit or every third visit because they’re doing so well and we’re very comfortable after 6 months or more of both response and tolerance. But those first 3 months, particularly for bladder cancer patients who have decreased performance status, visceral disease, or bone disease, these are the group of patients whom I like to monitor very frequently. Sometimes, we’ll see them every week for symptom management if they’re really symptomatic.
And these are the group of patients where if they get any complications associated with the agent, they could easily end up in the hospital. And those rates are rare, thankfully, but they do happen. They happen a lot more when we use checkpoint inhibitors in combination, but even as single agents, about 10% of our patients will get serious adverse events that will require hospitalization.
And if you treat enough patients with bladder cancer with these agents, you’re going to see these complications, GI complications, diarrhea and colitis, pneumonitis. We’ve seen endocrinopathies, we’ve seen problems with severe rash. All land patients in the hospital with grade 3, even grade 4 complications. So, these are things not to be trifled with. They’re not to be managed lightly over the phone. These are things that patients are going to be unaware of the seriousness of their complications until perhaps it’s too late. So, it’s really incumbent on us to educate them, particularly in those first 3 to 6 months, and be on the lookout for these complications.
When I’m treating a patient with metastatic bladder cancer, I always put this into context for patients, and sometimes the historical context is scary, but it’s important for patients to know. This is a disease we haven’t done very well in for a long period of time. And when we’re particularly looking in the platinum-refractory setting, we’re looking at median survivals between 6 and 9 months. Patients absolutely need to know that because we’re going to give them a checkpoint inhibitor, and they very well may respond and get a dramatic effect and do wonderful. But there’s a subset of patients who are not going to respond at all or are going to respond very short periods of time. And for that group of patients and for their families, it’s ultimately really critical that we get them into hospice and supportive care measures quickly.
As excited as I am about checkpoint inhibitors in bladder cancer, if you take care of patients with this disease on a regular basis, you’re humbled enough to know that these patients can suffer and these patients can deteriorate very quickly. And they just may not have time to either benefit or tolerate a checkpoint inhibitor. So even in our practice where we’re trying to anticipate these patients and move quickly, we have some patients who get only 1 or 2 doses of checkpoint inhibitors and move on to hospice. And that’s not what we want to do, but sometimes this disease is bigger, stronger, and faster than we’d like.
So, probably the most important advice I can give to people is to be honest with patients up front about that risk. And again, it’s scary but they need to be scared. This is a tough disease. If they’re in the platinum-naïve setting, there’s a little bit more time. Median survivals are more like 10 months. Believe it or not, that extra 3 months is huge because patients can spend a few months in hospice. If you’ve got a 10-month median survival, even your patients shorter than that are going to have 4 or 5 months to see if they can respond to that first line of therapy. And so, using checkpoints in that setting gives us more time to prepare patients and to be hopeful and to give the benefit of the doubt. But in that platinum-refractory setting, that is where we have to be ready for a quick move to hospice. If not, then patients end up in the hospital, they end up with more complications, and that’s when we really run into patients unprepared for what lies ahead.