How Will ESMO 2025 Data Shape the Future of Genitourinary Cancer Care?

The upcoming European Society for Medical Oncology Congress (ESMO) 2025 is poised to reveal key advances and potential breakthroughs in the management of several cancer types. On top of new data in the breast and lung cancer fields, the congress will exhibit noteworthy updates in genitourinary malignancy care.

To learn more about the presentations and late-breaking abstracts to look out for in genitourinary oncology, CancerNetwork^® connected with Oncology Decoded hosts Benjamin Garmezy, MD, and Manojkumar Bupathi, MD, MS. They outlined the sessions that may signal a shift in standards of care across different prostate and bladder cancer populations.

Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers. Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers.

LBA6: Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition).

Presentation: October 19, 5:14 – 5:24 PM CEST by Scott T. Tagawa, MD, MS, FACP, FASCO

“ESMO 2025 has the potential to make some groundbreaking changes for patients with genitourinary cancers. One of the most exciting spaces that may soon see a paradigm shift [is] metastatic hormone-sensitive prostate cancer [HSPC],” Garmezy stated in a written correspondence to CancerNetwork®. “Currently, the backbone of therapy is traditional androgen deprivation therapy [ADT] and an androgen receptor pathway inhibitor [ARPI] with the option to intensify with 6 cycles of docetaxel in high-risk [or] high-volume patients.”

According to Garmezy, one notable presentation that will shed light on a potential additional option for intensified therapy in this space relates to updated results from the phase 3 PSMAddition trial (NCT04720157). In this trial, investigators assessed lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus ADT and ARPIs among patients with prostate-specific membrane antigen (PSMA)–positive metastatic HSPC.

In June 2025, developers announced topline findings from PSMAddition showing that combining lutetium Lu 177 with standard of care (SOC) significantly improved radiographic progression-free survival (rPFS) vs SOC alone in this population.¹ Additionally, investigators noted a positive trend in overall survival (OS) favoring the lutetium Lu 177 arm at the time of analysis.

The FDA previously approved lutetium Lu 177 as a treatment for those with PSMA-positive, metastatic castration-resistant prostate cancer (CRPC) who received prior ARPIs in March 2025 based on data from the phase 3 PSMAfore trial (NCT04689828).² Investigators intend to submit detailed findings from the PSMAddition trial to regulatory authorities in the second half of 2025; these data may support the expanded use of lutetium Lu 177 in an earlier treatment setting.

2383O: A phase III study of capivasertib (capi) + abiraterone (abi) vs placebo (pbo) + abi in patients (pts) with PTEN deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC): CAPItello-281.

Presentation: October 19, 11:19 – 11:29 AM CEST by Karim Fizazi, MD, PhD

Garmezy and Bupathi highlighted an upcoming presentation on the phase 3 CAPItello-281 trial (NCT04493853) as one that may pose implications for the HSPC treatment algorithm. Impending data will reveal how treatment with capivasertib (Truqap) plus abiraterone compares with abiraterone alone among patients with PTEN-deficient de novo metastatic HSPC.

In November 2024, investigators shared topline results from the CAPItello-281 trial, which demonstrated a clinically meaningful and statistically significant rPFS improvement with the addition of capivasertib to abiraterone and ADT in this HSPC population.³ The experimental combination also produced an early trend towards improved OS, although data were immature at the time of analysis.

The safety profile of the capivasertib combination in CAPItello-281 appeared to be comparable with the known profiles of each individual agent. Presenting study investigator Karim Fizazi, MD, PhD,of Institut Gustave Roussy and University of Paris Saclay in Villejuif, France, noted that these trial data “represent a step forward” for patients with PTEN-deficient disease.³

“If positive, intensification choices may expand to PARP [inhibitors], docetaxel, lutetium Lu 177, or capivasertib,” Bupathi wrote regarding the upcoming presentations on the CAPItello-281 and PSMAddition trials. “An excellent problem that reflects real progress for patients.”

LBA2: Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: the phase III KEYNOTE-905 study

Presentation: October 18, 5:14 – 5:26 PM CEST by Christof Vulsteke, MD, PhD

Beyond the prostate cancer realm, Garmezy and Bupathi described how updated findings from the phase 3 KEYNOTE-905/EV-303 trial (NCT03924895) may be “instantly practice-changing” in the muscle-invasive bladder cancer (MIBC) space. Investigators of this randomized trial evaluated enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) before and after surgery compared with surgery alone among those who were ineligible to receive cisplatin.

Topline results from the first interim efficacy analysis shared in August 2025 showed that the enfortumab vedotin combination produced clinically meaningful and statistically significant improvements in event-free survival (EFS) and OS vs surgery alone.⁴ Furthermore, the experimental regimen reached the secondary end point of the pathological complete response rate.

At the time of this analysis, presenting investigator Christof Vulsteke, MD, PhD, head of Integrated Cancer Center Ghent (IKG, Belgium) and Clinical Trial Unit Oncology Ghent, said that data from the KEYNOTE-905 trial represent “the first time a systemic treatment approach, used before and after surgery, significantly extended survival over [SOC] surgery in this population,” suggesting that the enfortumab vedotin regimen may “address a critical unmet need.”⁴

References

1. Novartis Pluvicto™ demonstrates statistically significant and clinically meaningful rPFS benefit in patients with PSMA-positive metastatic hormone-sensitive prostate cancer. News release. Novartis. June 2, 2025. Accessed June 14, 2025. https://tinyurl.com/fedzdhfx
2. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. News release. FDA. March 28, 2025. Accessed October 14, 2025. https://tinyurl.com/y77tmenc
3. TRUQAP® (capivasertib) combination in PTEN-deficient metastatic hormone-sensitive prostate cancer demonstrated statistically significant and clinically meaningful improvement in radiographic progression-free survival in CAPItello-281 phase III trial. News release. AstraZeneca. November 25, 2024. Accessed October 14, 2025. https://tinyurl.com/tnwmuwpk
4. PADCEV plus KEYTRUDA significantly improves survival for certain patients with bladder cancer when given before and after surgery. News release. Pfizer and Astellas Pharma. August 12, 2025. Accessed October 15, 2025. https://tinyurl.com/mtnvfvv2