Experts Revisit the Most Notable Data in GU Oncology From ASCO 2026

During the 2026 ASCO Annual Meeting, investigators gathered from around the world to share key data in prostate cancer, urothelial carcinoma, and other genitourinary (GU) malignancies.

To gain further perspective on the biggest news in GU cancers coming out of the meeting, OncLive gathered insights from the following experts:

• Daniel V. Araujo, MD, a medical oncologist specializing in genitourinary malignancies at the University of Florida Health in Gainesville.
• Alicia Morgans, MD, MPH, a physician and the medical director of the Survivorship Program at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School in Boston, Massachusetts.
• Gopa Iyer, MD, the section head of the Bladder Cancer Department at Memorial Sloan Kettering Cancer Center in New York, New York.

Perioperative (neoadjuvant and adjuvant) apalutamide (APA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with radical prostatectomy (RP) in high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): Final analysis of the PROTEUS phase 3 study (LBA1)

Findings from the phase 3 PROTEUS trial (NCT03767244), which were simultaneously published in the New England Journal of Medicine, demonstrated that apalutamide (Erleada) plus androgen deprivation therapy (ADT; n = 1057) reduced the risk of metastasis or death by 20% vs placebo plus ADT by blinded independent central review in patients with high-risk localized or locally advanced prostate cancer (HR, 0.80; 95% CI, 0.67-0.96; P = .02).¹ The investigator-assessed metastasis-free survival (MFS) benefit with the investigational regimen was also shown to be consistent (HR, 0.74; 95% CI, 0.62-0.87; P = .0004).

The apalutamide regimen also led to a 9-fold improvement in the rate of pathologic complete response/minimal residual disease (pCR/MRD) at radical prostatectomy at 8.9% (n = 94) vs 1.0% (n = 10) with placebo plus ADT (OR, 10.17; 95% CI, 5.27-19.64; P < .0001). More than half of the responses in the apalutamide arm were pCRs. An exploratory analysis of residual cancer burden corroborated the pCR/MRD findings at 30.6% vs 11.7%, respectively (OR, 3.36; 95% CI, 2.67-4.23; P < .0001).

TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations (LBA5007)

Data from the phase 3 TALAPRO-3 trial (NCT04821622) revealed that the combination of talazoparib (Talzenna) and enzalutamide (Xtandi) led to a 52% reduction in the risk of radiographic progression or death vs placebo plus enzalutamide in patients with metastatic castration-resistant prostate cancer harboring homologous recombination repair (HRR) gene alterations.²

At a median follow-up of 37.6 and 37.7 months in these respective arms, the median radiographic progression-free survival (rPFS) by investigator assessment was not reached (NR; 95% CI, NR-NR) with talazoparib plus enzalutamide (n = 300) vs 45.8 months (95% CI, 37.7-NR) with placebo plus enzalutamide (n = 299; HR, 0.481; 95% CI, 0.357-0.647; P < .0001). The 36-month rPFS rates were 76.6% (95% CI, 70.8%-81.4%) and 56.2% (95% CI, 50.0%-62.0%), respectively. This rPFS benefit was observed in both biomarker-defined subgroups. In patients with BRCA1/2 alterations, talazoparib plus enzalutamide reduced the risk of radiographic progression or death by about 63% (HR, 0.368; 95% CI, 0.222-0.609; P < .0001); in the non–BRCA-mutated HRR subgroup, the reduction was approximately 43% (HR, 0.567; 95% CI, 0.392-0.819; P = .0022).

Enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy for previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): 3.5-year follow-up and response analyses from the phase 3 EV-302 study (abstract 4507)

Results from the 3.5-year follow-up of the phase 3 EV-302/KEYNOTE-A39 study (NCT04223856) showed that, at a median follow-up of 42.8 months, enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda; n = 442) generated a median overall survival (OS) of 33.6 months (95% CI, 26.6-39.8) vs 15.9 months (95% CI, 13.6-18.3) with chemotherapy (n = 444) in patients with previously untreated locally advanced or metastatic urothelial carcinoma (HR, 0.53; 95% CI, 0.45-0.63).³ The respective 42-month OS rates were 44.0% and 24.6%.

In the enfortumab vedotin arm, the overall response rate was 67.5%, including complete response (CR) and partial response (PR) rates of 30.4% and 37.1%, respectively. In the chemotherapy arm, these respective rates were 44.2%, 14.5%, and 29.7%. In the enfortumab vedotin arm, 10.3% of patients achieved a CR directly, and 20.1% of patients achieved a CR after a PR. These rates were 5.9% and 8.6%, respectively, in the chemotherapy arm.

References

1. Taplin ME, Gleave M, Shore ND, et al. Perioperative (neoadjuvant and adjuvant) apalutamide (APA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with radical prostatectomy (RP) in high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): final analysis of the PROTEUS phase 3 study. J Clin Oncol. 2026;44(suppl 17):LBA1. doi:10.1200/JCO.2026.44.17_suppl.LBA1
2. Agarwal N, Matsubara N, Azad A, et al. TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2026;44(suppl 17):LBA5007. doi:10.1200/JCO.2026.44.17_suppl.LBA5007
3. Powles T, Van Der Heijden MS, et al. Enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy for previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): 3.5-year follow-up and response analyses from the phase 3 EV-302 study. J Clin Oncol. 2026;44(suppl 16):4507. doi:10.1200/JCO.2026.44.16_suppl.4507