Apolo Discusses Managing Immune-Related Toxicities in Bladder Cancer

Andrea Apolo, MD

The undoubtable highlight of 2017 in bladder cancer is the bundle of FDA-approved PD-1/PD-L1 inhibitors. While these achievements are worth noting, Andrea Apolo, MD, stresses the importance of recognizing and managing immune-related toxicities associated with their use.

Considering there were 5 FDA approvals of checkpoint inhibitors in the last 18 months, it is becoming a growing necessity for urologists to understand how to distinguish immune-related adverse events (AEs) and appropriately manage patients with them, says Apolo.

While most immune-related toxicities are easily managed, there are some that can be severe and even life-threatening. In these instances, urologists should reach out to other healthcare professionals and utilize the available tools and guidelines in order to provide optimal care for their patients.

OncLive: This was a banner year for bladder cancer. What have been the biggest advances?

Can you discuss the management of immune-related toxicity with checkpoint inhibitors in bladder cancer?

Can you share your insight on how to manage these toxicities?

In an interview with OncLive during the 2017 Society of Urologic Oncology Annual Meeting, Apolo, chief of the Bladder Cancer Section of the Genitourinary Malignancies Branch at the National Cancer Institute, discussed these immune-related AEs, advised urologists on optimal management, and reflected on 2017 successes in bladder cancer.Apolo: 2017 has been a big year for bladder cancer with multiple FDA approvals of checkpoint inhibitors for the treatment of this disease. A lot of the exciting things that we are seeing now are combination therapies and how these [checkpoint inhibitors] are being moved to earlier states of disease, such as non-muscle invasive bladder cancer and muscle invasive bladder cancer. 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 2 active agents together and see the efficacy in patients with advanced bladder cancer. [Combinations] are also being looked at in non-advanced bladder cancer, as well.This year, at the 2017 SUO Annual Meeting, I was asked to talk about immune-related toxicities for patients with bladder cancer receiving checkpoint inhibitors. This is an important topic for urologists, because one of the strategies that we are doing as [investigators], now that we have seen activity in the second-line setting, is to move these agents to an earlier state of disease, such as muscle-invasive and non-muscle invasive bladder cancer. Urologists will be seeing these patients treated with checkpoint inhibitors in their clinic, so it is important that they know how to manage these toxicities. One of the most important things about managing an immune-related toxicity is recognizing it early. Most immune-related toxicities are easily manageable; however, there are rare, serious, life-threatening toxicities that need to be recognized early. I say: educate the patient, educate the nurses, and make sure that they pick up on subtleties. A lot of these AEs can be non-specific, such as fatigue and headache. It is important to recognize these early so that you can intervene early.

There are great guidelines out there for the management of immune-related toxicities. Each company has algorithms within the investigative brochure, there are the ESMO guidelines for immune-related toxicities, and [healthcare professionals] should always involve consult service for whatever organ type is having the immune-related toxicity.

Are there any red flags that urologists or community oncologists should look out for?

Is there anything exciting that we are expecting in 2018?

Talk to colleagues who have a lot of experience in dealing with these immune-related toxicities, because they are rare so not everyone has experience in managing them. Involve as many people as possible; there are great tools to use to manage these toxicities in patients with bladder cancer.It is very important to be thorough in your review of systems when you are evaluating patients receiving checkpoint inhibitors, because there can be a lot of subtleties. Have the patient talk to you about fatigue, get lab values to check for endocrine abnormalities, send patients with headaches or blurry vision to the ophthalmologist, and get MRIs in patients when you are unsure why they are having persistent headaches. Being aggressive in evaluating symptoms is important, because many of these can be severe and life-threatening. I am very excited to see the results of the first-line randomized trials for patients with bladder cancer where immunotherapy is being compared with chemotherapy. That is going to be really important and will be a question that we have as to what the activity is in cisplatin-eligible patients with bladder cancer. How does it compare with chemotherapy in the frontline setting?