Immune Checkpoint Inhibitors Demonstrate Safety in Genitourinary Cancers


In an interview with Targeted Oncology, Brian Ramnaraign, MD, further discussed the safety of immune checkpoint inhibitors in patients with genitourinary cancers.

Brian Ramnaraign, MD

Brian Ramnaraign, MD

When treated with at least 1 dose of an immune checkpoint inhibitor (ICI), most patients aged 65 years and older with upper tract urothelial carcinoma had mild or no immune-related adverse events (irAEs), according to findings from a retrospective study.1

The study included 139 patients aged 65 and older with kidney, bladder, and upper tract urothelial carcinoma. Between January 2018 and September 2022, these patients were treated at the University of Florida Health Cancer Center with at least 1 dose of pembrolizumab (Keytruda), nivolumab (Opdivo), or ipilimumab (Yervoy) with nivolumab, avelumab (Bavencio), or atezolizumab (Tecentriq).

The median age of patients was 74 (range, 65-93), with the majority of the patients being male (78%). Fifty-six patients (40%) had bladder cancer, 58 patients (42%) had kidney cancer, and 25 patients (18%) had upper tract urothelial carcinoma.

Findings showed that 76 (55%) patients had an irAE and 63 patients (45%) had no documented irAEs. Fifteen (11%) patients had a grade 1 toxicity, 41 (29%) patients had a grade 2 toxicity, 18 (13%) patients had a grade 3 toxicity, and 2 (1%) patients had a grade 4 toxicity. No grade 5 toxicities were observed in the study, and no deaths were directly linked to treatment.

Bladder Cancer, Urinary Bladder Image: © reineg -

Bladder Cancer, Urinary Bladder Image: © reineg -

Further, oral or intravenous steroids were given to 27 patients (19%) to manage their irAE, 16 (12%) patients discontinued treatment due to their irAE, and 12 (9%) patients underwent inpatient hospitalization due to their irAE.

Overall, these data show that severe AEs are uncommon among these patients with kidney, bladder, and upper tract urothelial carcinoma treated with an ICI, and patients rarely require hospital admissions.

In an interview with Targeted OncologyTM, Brian Ramnaraign, MD, an assistant professor of medicine in the division of hematology and oncology at the University of Florida College of Medicine, further discussed the safety of ICIs in patients with genitourinary cancers.

Targeted Oncology: What is the current role of immune checkpoint inhibitors in space?

Ramnaraign: Immune checkpoint inhibitors have revolutionized the care of patients with advanced genitourinary cancers. Currently, immune checkpoint inhibitors are used as first-line therapy for patients with advanced clear cell kidney cancer, and it's also used as maintenance therapy in patients with advanced urothelial carcinoma. In the adjuvant setting for both kidney and bladder cancer, it is used, so a lot of patients are getting checkpoint inhibitors as a part of their care.

Can you provide an overview of your research on ICIs in patients with advanced urinary cancers?

Our project was an analysis on the safety of immune checkpoint inhibitors and older patients with advanced genitourinary cancers. It was a retrospective study that we conducted at the University of Florida where we looked at patients with advanced kidney, bladder, and upper tract urothelial carcinoma who were treated with an immune checkpoint inhibitor between 2018 to 2022. We collected all data related to their treatment and to adverse events that they may or may not have experienced during that time.

What were the findings from this study?

What we found was that there were about 139 patients who were treated, and about half of those patients, or 45% to be exact, had no adverse events documented. Fifty-five percent of patients did experience some toxicity during their treatment. With regards to toxicities, most of the toxicities were low-grade toxicities, so grade 1 or 2 toxicities, and then about 14% of patients in the overall population experienced a grade 3 or higher toxicity or serious adverse event. When we look at the patients who experienced a serious adverse event, we had no grade 5 toxicities. That means that no patient had a toxicity that was associated or the cause of their death. In that patient population as well, only 2 patients had a grade 4 toxicity. One patient developed diabetic ketoacidosis and one other patient developed severe reactive arthritis. That patient had underlying rheumatoid arthritis. The vast majority of these severe adverse events were grade 3 toxicities and the most common of those were pneumonitis, diarrhea, transaminitis, and adrenal insufficiency.

The most common low-grade toxicities were hypothyroidism, which was easily correctable with the addition of levothyroxine. In the overall population, 19% of patients in the overall population required steroids, 9% of patients were hospitalized, and only 12% of patients had to discontinue because of the toxicity. What we found was that overall immune checkpoint inhibitors were very safe in patients in the geriatric population aged 55 and older, with very few developing severe toxicities or needing steroids becoming hospitalized because of an immunotherapy toxicity. Overall, what our study shows is that these drugs can be safely used in this patient population, but this data should be part of a greater discussion between the patient and the provider as to the risks and benefits and goals of such treatment.

In this study, how were toxicities managed?

When an immunotherapy toxicity occurred, specifically whether it was a severe toxicity, a grade 3 or higher toxicity, patients commonly received steroids. Steroids are the usual treatment when it comes to treating an immunotherapy toxicity. If it's a mild to moderate toxicity, usually patients can receive prednisone, which is an oral steroid, which is taken outpatient, so they can take it at home. But in patients who require hospitalization when it's a severe toxicity, usually they get [intravenous] steroids called methylprednisolone. In the case of severe toxicity, they're steroid refractory, we have to add in other immunosuppressants, but usually that's uncommon. When it comes to endocrine toxicities, usually we can just replace the hormone that the patient is deficient in. So in hypothyroidism, we can give the patient levothyroxine and in adrenal insufficiency, we can give patients hydrocortisone.

What was the purpose of this study? What are the key takeaways?

We wanted to evaluate this because in the clinical trials that have led to the approval of these drugs, the average age of the patients are actually in the low 60s, whereas in the real-world patients with advanced genitourinary cancers, the median age is the upper 60s. We see patients who are much older in clinical practice. In our study, where we found 139 patients over the past 4 years, the median age was actually 74. Our study is looking more at a real-world patient population.

What was interesting about our study too is we included several patients above the age of 85. I believe we had 18 patients who were 85 and older, including a few in their 90s who were treated with immune checkpoint inhibitors. I think this just adds to the growing body of evidence that suggests and supports the use of immune checkpoint inhibitors in this patient population, as long as they meet the FDA approvals and the current guidelines on care for this disease.

What ongoing research on this topic can you discuss?

For ongoing research, I think we're looking not just at safety, but efficacy with some of these drugs. We're looking at using checkpoint inhibitors in combination with other agents to try to improve patients efficacy. Our study was about safety, which is a huge concern in patients with advanced, incurable disease. We do want to try to improve outcomes in this patient population, but we don't want the risks to outweigh any potential benefits. Going back to our study, this class as a whole is fairly safe in this patient population. But the rest of the benefits of this drug class obviously should be discussed in detail with the patients and they should understand that there is a risk, but that overall in this patient population, it does seem to be fairly safe.

Ramnaraign BH, Patel NJ, Chatzkel JA, et al. Safety of checkpoint inhibitors in older patients with genitourinary cancers. J Clin Oncol. 41, 2023 (suppl 16) doi:10.1200/JCO.2023.41.16_suppl.12059. 12059.
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