What Were The Most Impactful GU Oncology Data From ESMO 2025?

Following the European Society for Medical Oncology (ESMO) Congress 2025, Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, met to discuss the presentations and data sets that may have the biggest impacts across genitourinary (GU) cancer care. Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers.

Bupathi and Garmezy outlined the top 5 abstracts from the meeting that have the potential to change or inform clinical practice across different GU malignancies. Notable presentations in bladder cancer, prostate cancer, kidney cancer, and other patient populations included the following:

#5: Phase 3 CAPItello-281 Trial (NCT04493853)

In the CAPItello-281 trial, combining capivasertib (Truqap) with abiraterone acetate, prednisone, and androgen deprivation therapy (ADT) prolonged radiographic progression-free survival (rPFS) among patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (HSPC).¹ Data revealed a median rPFS of 33.2 months (95% CI, 25.9-44.2) in the capivasertib arm vs 25.7 months (95% CI, 22.0-29.9) in the placebo arm (HR, 0.81; 95% CI, 0.66-0.98; P = .034).

#4: Phase 3 RC48-C016 Trial (NCT05302284)

Combining disitamab vedotin (PF-08046051) with toripalimab-tpzi (Loqtorzi) in the frontline setting significantly improved outcomes vs standard chemotherapy among patients with HER2-expressing locally advanced or metastatic urothelial carcinoma, according to data from the RC48-C016 trial.² Per blinded independent review committee (BIRC) assessment, the median PFS was 13.1 months (95% CI, 11.1-16.7) in the disitamab vedotin arm and 6.5 months (95% CI, 5.7-7.4) in the chemotherapy arm (HR, 0.36; 95% CI, 0.28-0.46; P <.0001). Additionally, the median overall survival (OS) was 31.5 months (95% CI, 21.7-not evaluable [NE]) vs 16.9 months (95% CI, 14.6-21.7) in each respective arm (HR, 0.54; 95% CI, 0.41-0.73; P <.0001).

#3: Phase 3 RAMPART Trial (NCT03288532)

Findings from the RAMPART trial showed that adjuvant therapy with durvalumab (Imfinzi) plus tremelimumab-actl (Imjudo) following renal cell carcinoma (RCC) resection improved disease-free survival (DFS) compared with active monitoring.³ The 3-year DFS rates were 81% in the durvalumab/tremelimumab arm vs 73% in the active monitoring arm across the intent-to-treat (ITT) population (HR, 0.65; 95% CI, 0.45-0.93; P = .0094). Additional data revealed that the DFS benefit associated with the durvalumab combination may have been driven by outcomes observed in the higher-risk population (HR, 0.52; 95% CI, 0.34-0.80; P = .0016).

#2: Phase 3 PSMAddition Trial (NCT04720157)

Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus ADT and an androgen receptor pathway inhibitor (ARPI) demonstrated statistically significant improvements in rPFS among patients with prostate specific-membrane antigen (PSMA)–positive metastatic HSPC in the PSMAddition trial.⁴ Data showed improvements with the lutetium Lu 177 vipivotide tetraxetan regimen vs an ARPI plus ADT alone in terms of rPFS (HR, 0.72; 95% CI, 0.58-0.90; P = .002) and OS (HR, 0.84; 95% CI, 0.83-1.13; P = .125).

#1: Phase 3 KEYNOTE-905/EV-303 Trial (NCT03924895)

Findings from the KEYNOTE-905/EV-303 trial showed improvements in event-free survival (EFS) among patients with muscle-invasive bladder cancer (MIBC) who were not eligible for or refused cisplatin-based chemotherapy following treatment with perioperative enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) with radical cystectomy and standard pelvic lymph node dissection.⁵ The median EFS was not reached (NR; 95% CI, 37.3-NR) in the enfortumab vedotin arm vs 15.7 months (95% CI, 10.3-20.5) in the control arm, in which patients underwent radical cystectomy and standard pelvic lymph node dissection followed by observation (HR, 0.40; 95% CI, 0.28-0.57; P <.0001).

References

1. Fizazi K, Clarke NW, De Santis M, et al. 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. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 2383O.
2. Sheng X, Zeng G, Zhang C, et al. Disitamab vedotin (DV) plus toripalimab (T) versus chemotherapy (C) in first-line (1L) locally advanced or metastatic urothelial carcinoma (la/mUC) with HER2-expression. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA7.
3. Larkin J, Powles TB, Frangou E, et al. First results from RAMPART: an international phase III randomised-controlled trial of adjuvant durvalumab monotherapy or combined with tremelimumab for resected primary renal cell carcinoma (RCC) led by MRC CTU at UCL. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA93.
4. Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA6.
5. Vulsteke C, Kaimakliotis HZ, Danchaivijitr P, et al. Perioperative enfortumab vedotin plus pembrolizumab in participants with muscle-invasive bladder cancer who are cisplatin-ineligible: phase 3 KEYNOTE-905 study. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA2.