Managing Toxicity Amidst Immunotherapy Expansion in Bladder Cancer Is Critical

After a long dry spell with no new agents to treat bladder cancer, the last year was astounding as the Food and Drug Administration (FDA) granted five approvals to immunotherapies in this space. Now, as more patients are being prescribed these therapies — both as monotherapies and in combination regimens – it is crucial to manage the immune-related side effects that may come along with them.

“We know what the efficacy is for monotherapy, so we are trying to do better. It is important to look out for toxicity in these combination regimens, but it is really exciting to take two active agents together and see the efficacy in patients with advanced bladder cancer,” Andrea Apolo, M.D., chief of the Bladder Cancer Section of the Genitourinary Malignancies Branch of the National Cancer Institute, said in an interview with OncLive, a sister publication of CURE. “Combinations are also being looked at in non-advanced bladder cancer.”

The 2017 immunotherapy approvals included the following:

• Opdivo (nivolumab) for the second-line treatment of locally advanced unresectable metastatic or advanced urothelial carcinoma that progressed on prior therapy;
• Tecentriq (atezolizumab) for the frontline treatment of cisplatin-ineligible patients;
• both Imfinzi (durvalumab) and Bavencio (avelumab), each for locally advanced or metastatic patients who progressed on prior therapy; and
• Keytruda (pembrolizumab) in both the frontline and second line settings for patients who are not eligible to receive cisplatin.

PD-1 and PD-L1 inhibitors work by helping the body to recognize cancer cells and getting the body to attack them. With that, patients often experience immune-related side effects — many of which resemble flu-like symptoms such as fatigue, fever and headache.

Whatever the side effect and however severe, it is crucial that patients alert their health care team about them. The sooner the better, Apolo said.

“One of the most important things about managing an immune-related toxicity is recognizing it early,” she said. “Most immune-related toxicities are easily manageable; however, there are rare, serious, life-threatening toxicities that need to be recognized early.”

Education plays a key role in making sure that patients, caregivers and members of the health care team can “pick up on the subtleties” of immune-related adverse events, according to Apolo. Fatigue, blurry vision and persistent headaches should always be reported, as they can end up being life-threatening.

“A lot of these adverse events can be non-specific, such as fatigue and headache. It is important to recognize these early so that you can intervene early,” she said.

This message will continue to be important as immunotherapy continues to be explored — either in additional bladder cancer settings or in comparison to chemotherapy.

“That is going to be really important and will be a question that we have as to what the activity is in cisplatin-ineligible patients with bladder cancer. How does it compare with chemotherapy in the frontline setting?” Apolo said.