Transcript Related Guidelines

What Are the Treatment Options for Stage IVB Bladder Cancer?

Tracy L. Rose, MD, MPH · University of North Carolina   


March 30, 2021

Editor’s Note: In consultation with the US Food and Drug Administration (FDA), AstraZeneca has withdrawn the indication of the monoclonal antibody durvalumab in previously treated adult patients with locally advanced or metastatic bladder cancer (mBC).[1]

In addition, in consultation with the FDA, Roche has withdrawn the indication of the monoclonal antibody atezolizumab in patients with previously treated mBC.[2]

This transcript has been edited for clarity.

Stage IVB bladder cancer refers to a cancer that has spread outside the bladder to other distant organs, and there is now, luckily, a substantial list of options for treatment of this bladder cancer, including several different types of drugs. Classic chemotherapy still remains the standard treatment recommendation for many patients with metastatic or stage IVB bladder cancer.[3,4]

The most commonly utilized drugs include what we call platinum-based chemotherapy, which includes the drug cisplatin and carboplatin in bladder cancer, which is typically given in combination with other chemotherapy drugs.[3,4,5,6] These chemotherapy drugs are associated with pretty typical side effects, including fatigue, suppressed immune system and blood counts (and thereby a risk of infection or bleeding), electrolyte abnormalities, and sometimes kidney injury, hearing trouble, or nerve damage. 

But there [are] also several other classes of drugs that have been approved in the last few years for treatment of stage IV bladder cancer, which has finally given us some options for treatment outside of standard chemotherapy, mainly immune checkpoint inhibitors, which are drugs that work on your own immune system to harness its ability to fight your cancer. So your immune system's job under normal conditions is to get rid of things that aren't supposed to be in your body, like viruses, bacteria, or even cancer. In metastatic bladder cancer, the cancer has evaded the immune system and grows despite this immune surveillance by your immune system. 

One way cancers do this is by putting proteins on their surface that interact with proteins on the surface of the immune cells and keep them from getting attacked. These immune checkpoint inhibitors block these proteins, thus retraining the immune system to recognize the cancer as foreign and kill it. Currently there [are] five drugs approved for bladder cancer that fall into this class of immune checkpoint inhibitors. These include atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab, and they all block similar proteins.[3] Patients typically will receive one of these agents since we don't know that giving one after another really does any good. 

Immune checkpoint inhibitors are most typically used after chemotherapy for stage IV bladder cancer, although a subset of patients do receive it as a first treatment if either they're unable to receive any platinum chemotherapies, or if they cannot receive the drug cisplatin, and their tumors also have these proteins called PD-L1 on the surface that might suggest a better response to immunotherapy. Additionally, a recent study called JAVELIN Bladder 100 showed that starting immunotherapy right after you finished chemotherapy actually improves survival for patients even whose tumors did not grow on chemotherapy.[3,4]

So the most standard treatment right now is chemotherapy followed immediately by immunotherapy. Additionally, there [are] a few other drugs that have been recently approved as options for metastatic or stage IV bladder cancer. Enfortumab vedotin is a drug in a class called an antibody-drug conjugate.[2] This means that it's a chemotherapy that is linked to an antibody that tries to target the cancer. 

This drug has been shown to have pretty exciting activity in patients [who] have received prior treatment for stage IV bladder cancers.[2] The major side effects include fatigue, neuropathy or numbness or pain in the extremities, rash, or hair and skin changes, gastrointestinal side effects like decreased appetite, nausea, vomiting, among others. 

There's also a drug called erdafitinib that's now a treatment option for some patients whose tumors have mutations or fusion in a receptor called the fibroblast growth factor receptor 2 or 3.[2] This drug is an oral drug so it's taken by mouth, but that does not necessarily mean that the side effects are any less than the other treatment options that we've discussed. Those can include electrolyte changes, eye problems, mouth ulcers, fatigue, diarrhea, nail and skin changes, among others. 

And lastly, clinical trials are a great option for many patients. Clinical trials can provide access to upcoming or unapproved drugs but also to promising combinations or drugs that we know work in later stages of the disease which are now being tested in earlier stages.[2]


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