Experts Break Down Practice-Informing Presentations From the 2025 Genitourinary Cancers Symposium

The 2025 Genitourinary (GU) Cancers Symposium concluded on Saturday, February 15, 2025, after 3 days of presentations showcasing emerging data across the fields of urothelial cancer, prostate cancer, and renal cell carcinoma (RCC). From practice-changing research to promising therapies in development, the following GU cancer experts shared their most notable takeaways in interviews with OncLive®:

• Tanya B. Dorff, MD, section chief, Genitourinary Disease Program, and professor, Department of Medical Oncology & Therapeutics Research, City of Hope
• Rohan Garje, MD, chief, Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute
• Robert Jones, MBChB, PhD, professor, clinical cancer research, University of Glasgow School of Medicine
• Bradley McGregor, MD, director, Clinical Research, Lank Center for Genitourinary Oncology, senior physician, and Marra Lochiatto investigator Dana-Farber Cancer Institute
• Funda Meric-Bernstam, MD, department chair, Department of Investigational Cancer Therapeutics, medical director, Department of Khalifa Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center
• Guru P. Sonpavde, MD, medical director, Genitourinary (GU) Oncology, assistant director, Clinical Research Unit, and Christopher K. Glanz Chair for Bladder Cancer Research, AdventHealth Cancer Institute

For those who missed the meeting in San Francisco, California, check out these experts’ perspectives and insights below!

Final Data From TALAPRO-2 Support the Use of Talazoparib Plus Enzalutamide in Unselected Patients With mCRPC

Garje: When we look at [metastatic castration-resistant prostate cancer (mCRPC), in] the update from the phase 3 TALAPRO-2 trial [NCT03395197], the all-comer cohort appeared to [experience] an overall survival [OS] benefit [with talazoparib (Talzenna) plus enzalutamide (Xtandi) vs placebo plus enzalutamide]. [However], we saw that the major benefit was [in] the homologous recombination–deficient [HRD] population.

Jones:The most provocative data we saw in prostate cancer were the survival data from TALAPRO-2. This was a trial in first-line mCRPC where [most patients] had not received a prior receptor pathway drug for metastatic hormone-sensitive prostate cancer. This is a slightly modern, slightly unusual population. [The trial] evaluated the combination of talazoparib and enzalutamide.

We have seen the data from the HRD population, [but in the] all-comers population, we [also saw] a statistically significant OS advantage [regardless of homologous recombination repair (HRR) mutation status], and that was a key secondary end point.

These drugs work in patients with BRCA mutations, and they probably work in [those with] some other HRD mutations. More provocatively, we’ve seen the breakdown of [those data] by fairly rigorously excluding patients with an HRD mutation. In the patients who did not harbor an HRD mutation, there still seems to be at least a strong trend [in favor of enzalutamide plus talazoparib]. This was an unplanned subgroup analysis, but even with those caveats, it seems that those patients still have a survival gain. We’ve [previously] seen a progression-free survival benefit in this subgroup of patients, but we had not seen that [OS] benefit. To my mind, that’s the question we needed to answer before we could offer [talazoparib plus enzalutamide] to all patients. Those are going to be important data [for informing] how we treat patients going forward.

McGregor: One of the more interesting presentations was on the role of talazoparib with enzalutamide in mCRPC, and whether we should be [using this combination in] patients who are [HRR-proficient]. We saw the data [showing] an OS signal in the intention-to-treat population. [However], that was driven a lot by those HRD, normally BRCA1/2–mutant, patients. As we get all these data, the question is: How do we incorporate them into care? That’s probably a more controversial topic.

NIAGARA Follow-Up Suggests Adjuvant Durvalumab May Provide Benefit in MIBC Regardless of pCR

Sonpavde: The single most practice-affecting abstract might be the long-term follow-up data from NIAGARA [NCT03732677]. NIAGARA was a large phase 3 study investigating neoadjuvant chemotherapy with or without durvalumab [(Imfinzi) in patients with muscle-invasive bladder cancer (MIBC)]. Durvalumab was given in the neoadjuvant phase and for 8 more cycles in the post-operative phase. The question for patients who achieve pathologic complete remission [pCR] with gemcitabine, cisplatin and durvalumab has always been: Do we need the adjuvant durvalumab component?

Notably, this regimen is still not approved. This analysis suggests that there was some benefit to the adjuvant component regardless of whether the patients achieved a pCR. At the moment, we are not at the point of saying that [patients] can live without the adjuvant component. Further studies need to be done incorporating circulation tumor DNA and perhaps predictive biomarkers to select patients who might benefit from adding durvalumab to gemcitabine and cisplatin. It’s interesting to see that both patients [who did and did not] achieve a pCR seemed to benefit, although the HRs seem more impressive in the pCR group.

Novel Targets and Updated Perioperative Data Reinforce Practice Patterns in Urothelial Cancer, But Sequencing Questions Remain

Garje: Updated data continue to show significant [benefit] with enfortumab vedotin-efjv [Padcev] in the metastatic setting for urothelial cancer. We can now communicate durable CR rates with patients. That enhances our confidence in that first-line agent.

There are a lot of new, upcoming agents targeting HER2, [as well as] newer variants of TROP2- and FGFR3-targeting agents in urothelial cancer. It’s an evolving area.

The perioperative space in MIBC has huge potential now with chemoimmunotherapy and HER2-based therapy. That is a paradigm that provides opportunities for cisplatin-ineligible or biomarker-selected patients.

There are also a lot of data on bladder-preservation strategies, including the update [from the phase 3 CheckMate 274 trial (NCT02632409) with] adjuvant nivolumab [Opdivo] showing a disease-free survival benefit and interim data suggesting an OS benefit [compared with placebo in patients with high-risk muscle-invasive urothelial carcinoma]. [Overall], there are a lot of new lessons from this meeting. Hopefully they improve our current practice patterns and re-emphasizes our treatment choices. There are a lot of new studies ongoing that will change our practice in the years to come.

Meric-Bernstam: There was quite a bit of debate [at the meeting]. It’s exciting to see how rapidly [the treatment paradigm is] changing, and there are still a lot of unanswered questions regarding how we sequence treatments. How do we give [treatment]? How do we decide on how to use immunotherapy in the adjuvant setting when we can bring in antibody-drug conjugates? We have much work to do over the next few years.

Mevrometostat May Be a New Treatment Approach in Abiraterone Acetate–Pretreated mCRPC

Dorff: The phase 3, randomized MEVPRO-1 study [NCT06551324] of mevrometostat [PF-06821497] in combination with enzalutamide [in patients with abiraterone acetate (Zytiga)–Pretreated mCRPC is showing] exciting data so far. [Mevrometostat is part of] a new class of drugs, and we’re always hoping to find new ways to attack prostate cancer beyond the modalities we have.

Final Results From COSMIC-313 Confirm No OS Advantage for Cabozantinib/Nivolumab/ Ipilimumab in Advanced RCC

McGregor: We have extended fallout for cabozantinib [Cabometyx] and nivolumab in [advanced clear cell RCC]. We saw the final analysis from [the phase 3 COSMIC-313 trial (NCT03937219)] showing that there’s no OS benefit to adding cabozantinib to nivolumab and ipilimumab [Yervoy]. A lot of trials, even though they may not be practice changing, are practice informing and will help us continue to move care forward.

To check out more of OncLive’s coverage from the 2025 GU Cancers Symposium, click here.