Bavencio Has Long-Term Benefit Regardless of Diabetes Status in Bladder Cancer

Treatment with Bavencio (avelumab) as first-line maintenance was associated with long-term efficacy and consistent safety in patients with advanced urothelial carcinoma regardless of if they had diabetes mellitus or not, according to research shared at the 2025 ASCO Genitourinary Cancers Symposium, Dr. Petros Grivas emphasized.

The JAVELIN Bladder 100 trial previously examined whether adding Bavencio to best supportive care improved survival in patients within this population, leading investigators to launch an explore exploratory analysis to examine if having diabetes affected treatment outcomes. While these findings suggest Bavencio is effective and safe for patients with or without diabetes mellitus, further research is needed to confirm these results, investigators concluded.

In an interview with CURE, Grivas sat down to discuss the topic of the sub-study and expanded on how these findings may influence treatment decisions for oncologists managing advanced urothelial carcinoma. Grivas currently serves as the clinical director of the Genitourinary Cancers Program and a professor in the Clinical Research Division at Fred Hutch Cancer Center, in Seattle, as well as a professor in the Division of Hematology and Oncology, at the University of Washington School of Medicine.

CURE: How does the presence of diabetes mellitus impact the effectiveness of immunotherapy in patients with advanced urothelial carcinoma?

Grivas: [Data] from the JAVELIN Bladder 100 phase 3 trial [showed] that switch maintenance with Bavencio — an anti-PD-1 immunotherapy —[demonstrated] significant overall and progression-free survival with Bavencio switch maintenance. We have conducted many studies since then, and the landscape continues to change. Obviously, we have practice-changing data [since then], so the landscape has changed significantly in the last few years.

A sub-study, [also called an] exploratory analysis, was conducted specifically looking at patients with and without diabetes mellitus. The key takeaway was that the benefit with Bavencio switch maintenance in the context of the JAVELIN Bladder 100 trial was independent of the presence of diabetes. Both patients with and without diabetes mellitus benefited from Bavencio switch maintenance therapy after responding to or achieving stable disease with platinum-based chemotherapy.

Given that diabetes is a common comorbidity, what precautions or modifications should be considered when treating patients with advanced urothelial carcinoma who have diabetes?

We have to take [medical comorbidities], like diabetes mellitus, into account when we treat patients. I always recommend very close follow-up with primary care providers and endocrinologists to optimize the treatment of diabetes mellitus. Diabetes, by itself, represents a significant risk for patients for cardiovascular disease and cardiovascular complications. I think this becomes even more relevant now that we use a lot of Padcev (enfortumab vedotin-ejfv) plus Keytruda (pembrolizumab).

The phase 3 EV-302/KEYNOTE-A39 trial demonstrated a significant overall and progression-free survival benefit with Padcev plus Keytruda versus platinum-based chemotherapy, making it the preferred standard of care. Padcev can cause hyperglycemia in about 10% of patients, so that makes it relevant to this discussion. We want patients with diabetes, both controlled and uncontrolled, to be followed closely by primary care providers and endocrinologists to optimize blood sugar control.

We have to pay very close attention to those patients regardless of treatment, and of course, while treating them with Padcev, to keep track of their blood sugar. We want to offer the best therapy to our patients with diabetes mellitus, and we need to pay extra attention to blood sugar and maintain very close follow-up. We should have a multidisciplinary approach in collaboration with primary care providers and endocrinologists for optimal control of diabetes mellitus, regardless of therapies.

As you said, the JAVELIN Bladder 100 trial showed prolonged overall and progression-free survival with Bavencioregardless of diabetes status. How should these findings influence treatment decisions for oncologists managing advanced urothelial carcinoma?

We have three practice-changing phase 3 trials: the JAVELIN Bladder 100 trial with switch maintenance Bavencio in patients with no progression after prior platinum-based chemotherapy; the CheckMate 901 trial, where gemcitabine plus cisplatin plus Opdivo (nivolumab) was better than gemcitabine plus cisplatin in cisplatin-eligible patients; and the EV-302 trial, with Keytruda plus Padcev, showing dramatic improvement in progression-free and overall survival compared with platinum-based chemotherapy.

I think, overall, Keytruda plus Padcev, based on the EV-302 trial, is the preferred standard of care. However, in many countries, this regimen or combination is not available due to lack of access or reimbursement. I think that's important to note because there are disparities in healthcare across different countries. Especially in countries where this Keytruda combination is not available, we have to consider even more the data from the JAVELIN Bladder 100 trial with switch maintenance Bavencio, particularly for patients who are cisplatin-ineligible and cannot receive cisplatin; the gemcitabine plus cisplatin plus Opdivo data do not apply to them.

The JAVELIN Bladder 100 trial remains the standard of care in countries where Keytruda plus Padcev is not available for cisplatin-ineligible patients. I think it's important to keep these three practice-changing trials in mind. We have to make the best individualized, personalized decision in clinical practice. We discuss the data with our patients. We take into account medical comorbidities, performance status, and organ function. We want to ensure we consider those relevant clinical factors when we make informed and shared decisions with our patients.

It's also important to hear our patients' priorities, wishes and treatment expectations, to consider efficacy data, toxicity data, quality of life and patient-reported outcomes data. To make informed decisions with our patients, we want to use the best treatment we have upfront. At the same time, we have to consider the particular details and specific context for individual patients.

What further research is needed to better understand the interplay between diabetes, immune response and treatment outcomes?

Diabetes is a common medical comorbidity in these patients and it, by itself, represents a risk for cardiovascular events. In terms of treatment, the highly relevant point is that Padcev can cause hyperglycemia in about 10% of patients, or one out of ten, and about half of those cases, around 5%, could potentially be severe and, in rare cases, life-threatening. So, we have to pay attention to the glucose levels of those patients, monitor their metabolic panels. [We must] work together with primary care providers and endocrinologists to optimize the control of diabetes, which can be beneficial across the board.

I think it's important to keep exploring data from different clinical trials and update the data sets with longer follow-up, and to look at different subsets of patients. Some of those subsets may be underpowered to give definitive answers, but they can at least generate hypotheses. It's definitely important to look at all those trials and try to keep updating the data, keep delving into relevant questions, and raising hypotheses that can be tested in subsequent trials.

Overall, the key is to synthesize these data sets and have a very informed, detailed discussion with our patients to help them make an informed decision.

Transcript has been edited for clarity and conciseness.

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