Top 5 Takeaways for Genitourinary Cancer Care From 2025 ASCO GU

In the adjuvant treatment of patients with muscle-invasive bladder cancer (MIBC), nivolumab (Opdivo) continued to demonstrate an improvement in disease-free survival vs placebo based on post hoc analysis data from the phase 3 CheckMate-274 trial (NCT02632409).

The 2025 ASCO Genitourinary Cancers Symposium exhibited several updates in the management of various genitourinary cancers, with late-breaking abstract presentations and poster sessions alike highlighting potential advancements in the treatment of patients with bladder cancer, prostate cancer, kidney cancer, and other malignancies. These findings elucidated how modalities such as tyrosine kinase inhibitors and antiandrogen agents may continue to impact the treatment paradigm.

CancerNetwork® covered the latest data outlined in these presentations. Here are the top 5 articles on the results that may influence clinical practice in genitourinary oncology:

#1: Adjuvant Nivolumab Shows Sustained DFS Benefit in High-Risk Bladder Cancer

In the adjuvant treatment of patients with muscle-invasive bladder cancer (MIBC), nivolumab (Opdivo) continued to demonstrate an improvement in disease-free survival vs placebo based on post hoc analysis data from the phase 3 CheckMate-274 trial (NCT02632409).1

Among all randomly assigned patients, the median DFS was 25.6 months (95% CI, 19.2-41.8) with nivolumab vs 8.5 months (95% CI, 7.3-13.7) with placebo (HR, 0.63; 95% CI, 0.51-0.78). Additionally, among those who received prior neoadjuvant chemotherapy, the median DFS was 19.6 months (95% CI, 15.6-48.2) vs 8.3 months (95% CI, 5.6-11.2) in each respective arm (HR, 0.58; 95% CI, 0.43-0.79). In a population of patients who did not receive prior neoadjuvant chemotherapy, the median DFS was 25.9 months (95% CI, 19.2-51.5) and 13.7 months (95% CI, 7.8-22.1) in each arm (HR, 0.69; 95% CI, 0.50-0.94).

“The improvements demonstrated in patients with MIBC provide additional support for adjuvant nivolumab as a standard of care for high-risk muscle-invasive urothelial carcinoma, including MIBC after radical surgery, and regardless of prior neoadjuvant chemotherapy,” Matthew I. Milowsky, MD, FASCO, The George Gabriel and Frances Gable Villere Distinguished Professor of Bladder and Genitourinary Cancer Research, co-leader of the University of North Carolina (UNC) Lineberger Clinical Research Program, section chief of Genitourinary Oncology, and co-director of the Urologic Oncology Program at UNC School of Medicine in Chapel Hill, said regarding these outcomes.

#2: Nivolumab/Cabozantinib Demonstrates Long-Term Efficacy in Advanced RCC

Final follow-up results from the phase 3 CheckMate 9ER trial (NCT03141177) showed that nivolumab (Opdivo) in combination with cabozantinib (Cabometyx) improved long-term efficacy with a manageable safety profile vs sunitinib (Sutent) in those with previously untreated advanced renal cell carcinoma (RCC).2

Data showed a median progression-free survival (PFS) of 16.4 months (95% CI, 12.5-19.3) in the nivolumab combination arm vs 8.3 months (95% CI, 7.0-9.7) in the sunitinib arm across the intent-to-treat (ITT) population (HR, 0.58; 95% CI, 0.49-0.70). In each respective arm, the median overall survival (OS) was 46.5 months (95% CI, 40.6-53.8) vs 35.5 months (95% CI, 29.2-42.8; HR, 0.79; 95% CI, 0.65-0.96). Study treatment yielded an overall response rate (ORR) of 55.7% (95% CI, 50.1%-61.2%) and 27.4% (95% CI, 22.7%-32.6%) in each arm.

“The results continue to support [nivolumab plus cabozantinib] as a standard of care for previously untreated advanced RCC,” according to Robert J. Motzer, section head of Kidney Cancer in Genitourinary Oncology Service and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center, and coauthors.

#3: Cabozantinib Combo Yields Sustained PFS at Follow-Up in Advanced RCC

A combination regimen consisting of cabozantinib, nivolumab, and ipilimumab (Yervoy) demonstrated a sustained PFS benefit compared with placebo plus nivolumab/ipilimumab among patients with advanced RCC in the phase 3 COSMIC-313 trial (NCT03937219).3

Final results from the study showed that the median PFS was 16.6 months (95% CI, 14.0-22.6) with the cabozantinib combination vs 11.2 months (95% CI, 9.3-14.0) with placebo plus nivolumab/ipilimumab in the ITT population (HR, 0.82; 95% CI, 0.69-0.98).

According to lead study author Laurence Albiges, MD, PhD, head of the Department of Oncology at Gustave Roussy in France, “there were no significant differences in OS between the 2 arms in the ITT population or by [International Metastatic Renal Cell Carcinoma Database Consortium] risk group.”

#4: Darolutamide/ADT Improves Outcomes in mHSPC Across Disease Volumes

Subgroup analysis data from the phase 3 ARANOTE trial (NCT04736199) exhibited improved efficacy when combining darolutamide (Nubeqa) with androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer regardless of disease volume.4

The median radiological PFS (rPFS) in patients with high-volume disease was 30.2 months (95% CI, 28.8-not reached [NR]) with darolutamide plus ADT vs 19.2 months (95% CI, 16.1-26.0) with placebo plus ADT (HR, 0.60; 95% CI, 0.44-0.80). In the low-volume disease subgroup, the median rPFS was NR (95% CI, NR-NR) in the darolutamide arm and NR (95% CI, 25.0-NR) in the placebo arm (HR, 0.30; 95% CI, 0.15-0.60).

“Efficacy outcomes with darolutamide plus ADT were improved vs placebo plus ADT regardless of disease volume,” Fred Saad, MD, FRCS, the director of prostate cancer research at the Montreal Cancer Institute, a uro-oncologist in the Urology Department, and a professor in the Department of Surgery at the Centre Hospitalier de l'Université de Montréal in Canada, stated regarding these findings.

#5: Avelumab Maintenance Extends Survival in Advanced Urothelial Carcinoma, Regardless of Diabetes

Combining maintenance avelumab (Bavencio) with best supportive care (BSC) improved OS and PFS in the first-line treatment of patients with advanced urothelial carcinoma across diabetes mellitus status subgroups in the phase 3 JAVELIN Bladder 100 trial (NCT02603432).5

The median OS was 20.8 months (95% CI, 18.0-32.4) with avelumab plus BSC vs 14.5 months (95% CI, 11.7-21.3) with BSC alone in patients with diabetes (HR, 0.60; 95% CI, 0.37-0.95); among those without diabetes, the median OS was 24.7 months (95% CI, 19.9-30.0) vs 15.8 months (95% CI, 13.3-18.7) in each respective arm (HR, 0.78; 95% CI, 0.64-0.96). In each arm, the median PFS was 5.6 months (95% CI, 3.7-9.3) vs 2.0 months (95% CI, 1.9-3.7) for patients with diabetes (HR, 0.50; 95% CI, 0.33-0.77) and 5.4 months (95% CI, 3.8-7.2) vs 2.1 months (95% CI, 1.9-3.5) for those without diabetes (HR, 0.54; 95% CI, 0.45-0.65).

“Overall, these results show that avelumab frontline maintenance is associated with long-term efficacy benefits and consistent safety in patients with advanced urothelial carcinoma with or without diabetes mellitus who are progression-free after first-line platinum-based chemotherapy,” according to lead study author Shilpa Gupta, MD, director of Genitourinary Medical Oncology at the Cleveland Clinic Taussig Cancer Institute in Ohio.

References

1. Milowsky MI, Galsky MD, Witjes JA, et al. Adjuvant nivolumab vs placebo for high-risk muscle-invasive urothelial carcinoma: additional efficacy outcomes including overall survival in patients with muscle-invasive bladder cancer from CheckMate-274. J Clin Oncol. 2025;43(suppl 5):658. doi:10/1200/JCO.2025.43.5_suppl.658
2. Motzer RJ, Escudier B, Burotto M, et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate 9ER trial. J Clin Oncol. 2025;43(suppl 5):439. 10.1200/JCO.2025.43.5_suppl.439
3. Albiges L, Motzer RJ, Trevino S, et al. Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC): final results of COSMIC-313. J Clin Oncol. 2025;43(5):438. doi:10.1200/JCO.2025.43.5_suppl.438
4. Saad F, Shore N, Vjaters E, et al. Darolutamide plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC) by disease volume: subgroup analysis of the phase 3 ARANOTE trial. J Clin Oncol. 2025;43(suppl 5):151. doi:10.1200/JCO.2025.43.5_suppl.151
5. Gupta S, Grivas P, Park SH, et al. Avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) with or without diabetes mellitus (DM): long-term outcomes from JAVELIN Bladder 100. J Clin Oncol. 2025;43(suppl 5):869. doi:10.1200/JCO.2025.43.5_suppl.869