A Look at Upcoming Impactful Presentations at ASCO GU 2025

Updated findings from the phase 3 NIAGARA trial (NCT03732677) at the 2025 Genitourinary Cancers Symposium may further elucidate how pCR status influences other treatment outcomes with durvalumab in combination with gemcitabine/cisplatin.

Experts in the genitourinary oncology field are almost ready to meet in San Francisco, CA, to present the newest developments across different genitourinary malignancies as part of the 2025 ASCO Genitourinary Cancers Symposium. The conference will feature several sessions revealing key findings on potentially practice-impacting modalities and novel therapies in the management of bladder cancer, prostate cancer, kidney cancer, and other patient populations.

Here are some of the presentations that may influence clinical decision-making across various genitourinary cancer disciplines.

659: Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA.

In a post on X,Amol Akhade, MD, a medical oncologist at Hiranandani Hospital (@SuyogCancer), identified the pathologic complete response (pCR) analysis from the phase 3 NIAGARA trial (NCT03732677) as a potentially “interesting” update at the meeting.¹ Investigators of this open-label, multi-center, international trial are evaluating durvalumab (Imfinzi) in combination with gemcitabine/cisplatin as neoadjuvant therapy followed by adjuvant durvalumab for patients with muscle-invasive bladder cancer (MIBC).²

The FDA previously granted priority review to durvalumab/chemotherapy as a treatment for those with MIBC in December 2024 based on prior data from the NIAGARA trial.³ These findings were presented in a presidential symposium session at the 2024 European Society for Medical Oncology (ESMO) Congress.⁴

Planned interim analysis data showed that the median event-free survival (EFS)—one of the trial’s coprimary end points—was not reached (NR; 95% CI, NR-NR) with perioperative durvalumab vs 46.1 months (95% CI, 32.2-NR) among those who received chemotherapy alone (HR, 0.68; 95% CI, 0.56-0.82; P <.0001). Regarding the key secondary end point of overall survival (OS), combining durvalumab with chemotherapy lowered the risk of death by 25% (HR, 0.75; 95% CI, 0.59-0.93; P = .0106).

With a data cutoff of April 2024, investigators observed nominal statistical significance associated with the other coprimary end point of pCR in the durvalumab arm (odds ratio [OR], 1.60; 95% CI, 1.23-2.08; P = .0005).

Updated findings from the NIAGARA trial at the 2025 Genitourinary Cancers Symposium may further elucidate how pCR status influences other treatment outcomes with the durvalumab combination. Additionally, these data may lend additional support to the supplemental biologics license application for the regimen in MIBC, which the FDA has assigned a Prescription Drug User Fee Act date in the second quarter of 2025.

658: Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk muscle-invasive urothelial carcinoma (MIUC): Additional efficacy outcomes including overall survival (OS) in patients (pts) with muscle-invasive bladder cancer (MIBC) from CheckMate 274.

On X, Guru P. Sonpavde, MD, a medical oncologist, program director of Genitourinary Oncology and Phase 1 New Drug Development, and Christopher K. Glanz Chair for Bladder Cancer Research at AdventHealth Cancer Institute, as well as a professor of Internal Medicine at the University of Central Florida (@sonpavde), highlighted a list of “potentially practice-impacting" presentations in bladder cancer at this year’s symposium.⁵ One of these presentations was an oral abstract session on updated results from the phase 3 CheckMate 274 trial (NCT02632409) assessing nivolumab (Opdivo) vs placebo in patients with MIBC.⁶

Adjuvant nivolumab previously earned FDA approval for treating patients with urothelial carcinoma at a high risk of recurrence following radical resection in August 2021 based on prior findings from the CheckMate 274 trial.⁷

At the time of approval, investigators noted that the median disease-free survival (DFS) among all patients was 20.8 months (95% CI, 16.5-27.6) with nivolumab vs 10.8 months (95% CI, 8.3-13.9) with placebo; nivolumab also reduced the risk of disease recurrence or death by 30% compared with placebo (HR, 0.70; 95% CI, 0.57-0.86; P = .0008). Additionally, among those with PD-L1 positivity in at least 1% of tumor cells, the median DFS was NR (95% CI, 21.2-NE) and 8.4 months (95% CI, 5.6-21.2) in each respective arm; the risk of disease recurrence or death was 45% lower with nivolumab than placebo (HR, 0.55; 95% CI, 0.39-0.77; P = .0005). Overall, nivolumab demonstrated improvements in the primary end points of DFS across the intent-to-treat population and among those with a PD-L1 expression level of 1% or higher.

According to previously published findings in The New England Journal of Medicine, the trial’s secondary end point of OS was planned to be formally compared with the use of a hierarchical procedure in each population and evaluated after additional follow-up.⁸ The investigators noted that further data on OS and other secondary and exploratory end points may “provide greater insight into the efficacy of nivolumab in this context.”

LBA18: Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial.

Another topic of interest that Akhade highlighted was the final OS results from the phase 3 TALAPRO-2 trial (NCT03395197), in which investigators assessed talazoparib (Talzenna) plus enzalutamide (Xtandi) vs enzalutamide monotherapy as frontline therapy for patients with metastatic castration-resistant prostate cancer (CRPC).⁹

Investigators announced topline results from the final prespecified OS analysis of the TALAPRO-2 study in October 2024.¹⁰ Of note, talazoparib/enzalutamide conferred a statistically significant and clinically meaningful OS improvement among all-comers and in those with homologous recombination repair (HRR) gene mutations vs enzalutamide alone. The late-breaking abstract at the symposium may specifically illustrate how much of a survival advantage the combination regimen demonstrated over enzalutamide monotherapy in these populations.

“These [OS] results indicate potentially practice-changing efficacy for [talazoparib] in combination with [enzalutamide] for [patients] with metastatic [CRPC]. Metastatic [CRPC] is the most advanced and aggressive stage of the disease, and the TALAPRO-2 results provide much-needed hope to patients who remain in high unmet need for effective treatment options,” lead trial investigator Neeraj Agarwal, MD, FASCO, professor and presidential endowed chair of Cancer Research at Huntsman Cancer Institute of University of Utah, stated in a press release on the topline results from the final prespecified analysis.¹⁰

The FDA previously approved talazoparib/enzalutamide for patients with HRR-mutated metastatic CRPC in June 2023 based on data from the TALAPRO-2 trial.¹¹

441: Casdatifan (Cas) monotherapy in patients (pts) with previously treated clear cell renal cell carcinoma (ccRCC): Safety, efficacy and subgroup analysis across multiple doses from ARC-20, a phase 1 open-label study.

Another presentation will highlight the safety and efficacy results, including subgroup analysis, of the phase 1b ARC-20 study (NCT05536141) evaluating casdatifan monotherapy in patients with clear cell renal cell carcinoma (RCC) previously treated with at least 2 prior lines of therapy.¹²

Topline data exhibited from the first available clinical data presented at the 2024 EORTC-NCI-AACR Symposium revealed that among patients with metastatic clear cell RCC treated with 50 mg of the investigational agent (n = 28) in a dose expansion cohort, the objective response rate (ORR) was 25.0% (90% CI, 10.7%-44.9%).¹³Additionally, the disease control rate (DCR) was 85.7% (90% CI, 67.3%-96.0%).

The dose escalation cohort of the trial followed a 3+3 design with doses ranging from 20-200 mg once daily. Patients with clear cell RCC previously treated in the metastatic setting who were HIF- 2α-inhibitor naïve assessed in the dose expansion cohort trial were given 50 mg of casdatifan twice daily. In the dose expansion cohort, no dose-limiting toxicities were observed at the data cut-off.

In a written correspondence with CancerNetwork^®, Wenxin Xu, MD, assistant professor of Medicine at Harvard Medicine School and medical oncologist at the Dana-Farber Cancer Institute, wrote that the investigational therapy is moving forward in numerous large trials and could have potential as an important new drug for patients with RCC.

437: Evaluation of circulating kidney injury marker-1 (KIM-1) as a prognostic and predictive biomarker in advanced renal cell carcinoma (aRCC): Post-hoc analysis of CheckMate 214.

In a written correspondence to CancerNetwork, Xu highlighted a post-hoc analysis of the phase 3 CheckMate 214 trial (NCT02231749) he will be presenting at the event. He stated that the findings “show the kidney injury marker (KIM)-1 blood test is an early indicator for efficacy of nivolumab plus ipilimumab (Yervoy) in advanced RCC,” further emphasizing that blood biomarkers may be integral in informing treatment decisions for this disease state.¹⁴

Data exhibited at the 2024 Kidney Cancer Research Summit showed that the median OS in the intent-to-treat population was 52.7 months (95% CI, 45.8-64.5) with nivolumab/ipilimumab vs 37.8 months (95% CI, 31.9-43.8) with sunitinib (Sutent; HR, 0.72; 95% CI, 0.62-0.83).¹⁵ In the respective arms, the median PFS was 12.4 months (95% CI, 9.9-16.8) vs 12.3 months (95% CI, 9.8-15.2; HR, 0.88; 95% CI, 0.75-1.03).

Patients with previously untreated advanced RCC were enrolled and randomly assigned 1:1 to receive 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for 4 doses followed by 50 mg of maintenance nivolumab or sunitinib orally once daily for 4 weeks as part of every 6-week cycle. OS, PFS, and ORR among those with intermediate- or poor-risk disease in the primary population were assessed. As part of a secondary analysis, the intent-to-treat population was evaluated and those with favorable risk were assessed in an exploratory analysis.

A previous study Xu contributed to published in the Journal of Clinical Oncology assessed whether plasma KIM-1 could be used as a risk stratification tool among patients with renal masses.¹⁶ Study findings revealed that the presence of plasma KIM-1 was associated with worse metastasis-free survival (HR, 1.29; 95% CI, 1.10-1.53) and OS (HR, 1.31; 95% CI, 1.10-1.54), as well as more malignant pathology.

506: Association of clinical characterization of renal cell carcinoma (RCC) with merlin protein deficiency and biallelic loss of NF2.

Another trial highlighted by Xu in a written correspondence was a single institutional cohort study assessing patients with RCC with merlin deficiency and biallelic NF2 loss, which Xu claims contains some of the first data for this subtype which has no standard treatment paradigm.¹⁷

Previous results published in Histopathology, revealed that merlin immunohistochemistry (IHC) was approximately 92% sensitive and about 94% specific for biphasic hyalinizing psammomatous (BHP)-RCC, suggesting that merlin IHC was a reliable surrogate marker in identifying NF2 gene inactivation.¹⁸ By contrast, in all papillary RCC, TFE3-translocation RCC, and TFEB-altered RCC, merlin was diffusely or multifocally expressed.

Additionally, a previous study presented at the 2024 American Society of Clinical Oncology (ASCO) Meeting found that unclassified RCC (uRCC) subtypes exhibited unique genomic profiles vs more common RCC subtypes, with NF2 alterations emerging as more frequent in uRCC with poorer prognoses.¹⁹ Of note, median OS was less favorable in patients with NR2-mutant uHCC at 30.4 months vs those without NR2 alterations at 86.5 months (P = .063).

In a post on X, presenting author Emre Yekeduz, MD, a medical oncologist at the Dana-Farber Cancer Institute (@yekeduz_emre), claimed that thestudy received the Conquer Cancer Merit Award from the ASCO Foundation for this meeting.²⁰

References

1. @SuyogCancer. What is interesting in ASCO GU25 #GU25 @ASCO . 1 - Surgery vs RT for High Risk Prostate cancer. -IPD Data from 2 RCT 2 -OS for checkmate274 3 - PCR analysis for Nigeria trial 4 - Final OS for Talapro-2 trial 5- management of biochemical recurrence after RT for localized ca prostate. 6 - management of oligometastatic prostate cancer. @OncBrothers @OncoAlert @Larvol. February 6, 2025. Accessed February 11, 2025. https://x.com/SuyogCancer/status/1887694533359771909
2. Galsky M, Van der Heijden M, Catto J, et al. Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA. J Clin Oncol. 2025;43(suppl 5):659. doi:10.1200/JCO.2025.43.5_suppl.659
3. Imfinzi granted Priority Review in the US for patients with muscle-invasive bladder cancer. News release. AstraZeneca. December 6, 2024. Accessed February 11, 2025. https://tinyurl.com/3cj6yvup
4. Powles T, Van der Heijden MS, Galsky M, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA5.
5. @sonpavde. #GU25: Key #bladdercancer presentations (in my opinion)- highlights and summary coming after the conference from @AdventHealthCFL #cancer Institute- please note @OncoAlert @Larvol @OncLive @GUOncologyNow @SWOG @DrNeilLove @PeerView @doximity. February 9, 2025. Accessed February 11, 2025. https://x.com/sonpavde/status/1888611496843759676
6. Milowsky M, Galsky M, Witjes J, et al. Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk muscle-invasive urothelial carcinoma (MIUC): additional efficacy outcomes including overall survival (OS) in patients (pts) with muscle-invasive bladder cancer (MIBC) from CheckMate 274. J Clin Oncol. 2025;43(suppl 5):658. doi:10.1200/JCO.2025.43.5_suppl.658
7. U.S. Food and Drug Administration approves Opdivo® (nivolumab) for the adjuvant treatment of patients with high-risk urothelial carcinoma. News release. Bristol Myers Squibb. August 20, 2021. Accessed February 11, 2025. https://tinyurl.com/bdz7dmme
8. Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102-2114. doi: 10.1056/NEJMoa2034442. Erratum in: N Engl J Med. 2021;385(9):864. doi: 10.1056/NEJMx210012.
9. Agarwal N, Azad A, Carles J, et al. Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. J Clin Oncol. 2025;43(suppl 5):LBA18.
10. Pfizer’s TALZENNA® in combination with XTANDI® prolongs overall survival in phase 3 TALAPRO-2 trial. News release. Pfizer. October 10, 2024. Accessed February 11, 2025. https://tinyurl.com/2p9p98he
11. FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. News release. FDA. June 20, 2023. Accessed February 11, 2025. https://bit.ly/3pcuSTH
12. Choueiri T, Lee JL, Merchan J, et al. Casdatifan (Cas) monotherapy in patients (pts) with previously treated clear cell renal cell carcinoma (ccRCC): safety, efficacy and subgroup analysis across multiple doses from ARC-20, a phase 1 open-label study. J Clin Oncol. 2025;43(suppl 5): Abstract 441
13. Choueiri T, Garmezy B, Park SH, et al. Casdatifan in patients (pts) with previously treated clear cell renal cell cancer (ccRCC) and other solid tumors; preliminary results from ARC20: a phase 1, open-label dose-escalation and expansion study. Eur J Cancer. 2024:211(suppl 1): Abstract 4
14. Xu W, Vemula SV, Motzer R, et al. Evaluation of circulating kidney injury marker-1 (KIM-1) as a prognostic and predictive biomarker in advanced renal cell carcinoma (aRCC): post-hoc analysis of CheckMate 214. J Clin Oncol. 2025;43(suppl 5): Abstract 437
15. Atkins MB, Escudier B, McDermott DF, et al. Nivolumab plus ipilimumab vs sunitinib for first-line treatment of advanced renal cell carcinoma: 8-year follow-up with analyses in favorable-risk patients from the phase 3 CheckMate 214 trial. Presented at the 2024 Kidney Cancer Research Summit; July 11-12, 2023; Boston, MA. Abstract 8.
16. Xu W, Gaborieau V, Niman SM, et al. Plasma kidney injury molecule-1 for preoperative prediction of renal cell carcinoma versus benign renal masses, and association with clinical outcomes. J Clin Oncol. Published online May 3, 2024. doi:10.1200/JCO.23.00699
17. Yekeduz E, Machaallani M, Siegmund S, et al. Association of clinical characterization of renal cell carcinoma (RCC) with merlin protein deficiency and biallelic loss of NF2. J Clin Oncol. 2025;43(suppl 5): Abstract 506
18. Collins K, Hwang M, Antic T, et al. Merlin immunohistochemistry is useful in diagnosis of tumours within the spectrum of biphasic hyalinizing psammomatous renal cell carcinoma. Histopathology. 2022;81(5):577-586. doi:10.1111/his.14731
19. Yekeduz E, Braun DA, Chedade REH, et al. Applying genomic analysis to refine unclassified renal cell carcinoma. J Clin Oncol. 2024;42(suppl 16):4551. doi:10.1200/JCO.2024.42.16_suppl.4551
20. @yekeduz_emre. 🎉💥🎉Happy to share that our study on merlin-loss RCC has been awarded @ConquerCancerFd "Merit Award" by @ASCO ! 🌟🌟🌟Many thanks to my greatest mentor @DrChoueiri , @MikeSerzanMD , and Dr. Michelle Hirsch along with all contributors to the study! 🎯Looking forward to #GU25 ! @MarcMachaalani @eddy_saad @RazaneHChehade @Clara__Steiner @BradMcG04 @VincentWenxinXu @PrafulRavi1 @bergsa83 @CharleneMantia #CancerAwareness #Oncology #Cancer @DanaFarber_GU @AnkaraUni @AUTF_DEKANLIK @harvardmed @OncoAlert. January 31, 2025. Accessed February 11, 2025. https://x.com/yekeduz_emre/status/1885297854505173019