Multidisciplinary Approaches to Managing IRAEs in RCC

At the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, a roundtable of expert panelists convened to discuss the latest research and practice updates related to advanced kidney cancer. Dr. Karine Tawagi of University of Illinois was joined by Drs. Regina Barragan-Carrillo, Benjamin Maughan, Laurence Albiges, and David McDermott in the discussion.

In the fifth part of the roundtable, the panel considers how managing real-world patients on novel therapies like belzutifan presents challenges such as pre-existing conditions impacting oxygen saturation, evolving toxicity management strategies, and the need for multidisciplinary collaboration, while education of ER teams and community oncologists remains crucial for effective immune-related adverse event management.

View the next segment on Expanding Treatment Horizons: Novel Approaches in RCC and Non-Clear Cell Disease.

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Dr. Tawagi: What challenges are you all seeing in real-world practice compared to the patients studied in clinical trials?

Dr. Albiges: Are we discussing this across all settings?

Dr. Tawagi: Well, I think we could focus on settings where we are seeing more elderly patients with RCC, more comorbidities, and we can also separately talk about non-clear cell RCC.

Dr. McDermott: If I had to answer that question, I would say that managing belzutifan in non-trial patients is a little more challenging. For example, patients with baseline COPD or other conditions that cause low oxygen saturation, what do you do when they walk into the clinic with an O2 saturation of 75 percent? It usually causes some concern at the front desk, but often these patients do not have any symptoms. So how do you manage that? Do you dose reduce or hold treatment? I have yet to have a patient experience significant issues in this setting, but I do find myself reducing the dose or holding the dose more in real-world settings than I did in clinical trials.

Dr. Tawagi: Right. Are you also seeing a lot of GI side effects affecting patient quality of life?

Dr. McDermott: Not necessarily with belzutifan.

Dr. Albiges: The good thing about combination therapy is that we have had more experience with single agents, particularly VEGF-TKIs, which has helped us manage toxicity more effectively. For example, we can offer drug holidays, alternative schedules, or off-treatment breaks. In Europe, at least in France, we cannot use IO-IO combinations due to reimbursement policies, so we rely on IO-TKI combinations. For good-risk patients, I am happy to achieve a great response and then offer an escalation like a drug holiday or withholding the TKI. I think we are now much better at managing toxicity. With belzutifan, we are still learning, but most of the toxicity we have encountered has been related to VEGF-driven or immune-mediated toxicity, which requires prompt management.

Dr. Tawagi: Yes, these novel agents come with new toxicity profiles, and we have discussed immune-related adverse events (IRAEs). These often require a multidisciplinary approach. When specific organs are affected at your institutions, do you have an IRAE team, or is it managed on a case-by-case basis?

Dr. Barragan-Carrillo: We are lucky that our approach to toxicities is managed by a team that is highly specialized in cancer care, as we are mostly a cancer-only center. When we need to consult specialists like GI or pulmonology, they are very familiar with the side effect profiles. However, I know this is not the reality everywhere. When I trained in Mexico, I often found myself as the oncologist being the only person who understood how certain toxicities would present and why some approaches worked better than others. So I think it is crucial to engage non-cancer-specific centers and practices, especially in global oncology. Managing toxicities is easier when you are in a room full of experts, but in day-to-day practice, most patients are not in that setting. I believe gaining experience with these drugs and reaching out to community practices is key to helping patients do better.

Dr. McDermott: I agree, and I think educating emergency room doctors is essential. They are often the first to evaluate and treat these patients, so getting it right matters. For example, I find my patients often receive broad-spectrum antibiotics in the ER when they do not necessarily need them. With data from City of Hope, we know that administering broad-spectrum antibiotics might not be ideal, especially if we are trying to preserve the gut flora, which could impact treatment response. Educating all the healthcare providers who may come into contact with these patients is crucial for better outcomes.

Dr. Maughan: To that point, I sometimes feel like a transplant doctor, where I educate my patients to make sure they tell every ER doctor, “I am a transplant patient.” In our case, I tell them to make sure they inform the ER staff that they are on a checkpoint inhibitor.

Dr. Tawagi: That is a great point. Some patients have IRAE wallet cards or alerts that inform healthcare providers about their immunotherapy treatment and the potential side effects to expect.

Dr. Maughan: Exactly. Many centers do not have specific IRAE treatment teams, so I am grateful for organizations like ASCO and NCCN, which have developed thoughtful treatment algorithms for managing IRAEs. These resources are invaluable to oncologists, especially those on the front lines managing these side effects for most patients.