What Were the Top 2026 ACSO Genitourinary Symposium Abstracts?

Genitourinary oncologists convened in San Francisco, California, to attend the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Key abstracts across genitourinary cancers were presented and included readouts of key trials examining pembrolizumab (Keytruda)-based combination regimens in renal cell carcinoma (RCC), a final overall survival (OS) analysis of the EORTC 1333/PEACE-3 trial (NCT02194842) evaluating enzalutamide (Xtandi) and radium-223 for the treatment of metastatic castration-resistant prostate cancer (CRPC), and findings from the phase 3 PSMAddition trial (NCT04720157) evaluating [¹⁷⁷Lu] Lu-PSMA-617 (Pluvicto) plus androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) in PSMA-positive metastatic hormone-sensitive prostate cancer (HSPC).

Could Pembrolizumab Bolster the Efficacy of Belzutifan in High-Risk Clear Cell RCC?

One key abstract presented at the trial was a readout of the phase 3 LITESPARK-022 study (NCT05239728) given by Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, coleader of the Kidney Cancer Program at Dana-Farber/Harvard Cancer Center, and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School.¹ Specifically, the analysis provided interim OS data on pembrolizumab with or without belzutifan (Welireg) among patients with histologically confirmed clear cell renal cell carcinoma (RCC) who did not receive prior systemic therapy.

Among patients treated with belzutifan (n = 921) vs those treated with placebo (n = 920), a disease-free survival (DFS) benefit emerged, although median DFS was not reached in either arm. The 24- and 30-month DFS rates per investigator assessment was 80.7% vs 73.7% and 75.8% vs 68.6% in the respective arms (HR, 0.72; 95% CI, 0.59-0.87; P = .0003).

Additionally, interim OS data revealed a non-significant advantage with belzutifan, with 24-month rates of 96.2% vs 95.7% with placebo, and 30-month rates of 95.6% vs 93.8%, respectively (HR, 0.78; 95% CI, 0.51-1.19; P = .1220).

A safety analysis revealed a greater incidence of grade 3 or higher treatment-emergent adverse effects (TEAEs) with belzutifan at 52.1% vs 30.2% with placebo. Moreover, 11.9% vs 9.0% led to discontinuation of study treatment, and 1.1% vs 1.2% led to death, respectively. Grade 3 or higher treatment-related AEs (TRAEs) occurred in 42.2% vs 17.9% of patients, respectively, with 10.2% vs 7.3% and 0.3% vs 0.3% leading to discontinuation or death, respectively.

“The safety profile of pembrolizumab and belzutifan was manageable with a low rate of AEs leading to the discontinuation of both study drugs and an overall safety profile that was consistent with the expected profiles of each individual drug,” Choueiri explained in the presentation. “These results support the addition of belzutifan to standard-of-care adjuvant pembrolizumab for patients with clear cell RCC at increased risk of recurrence.”

Does the Addition of an Alpha-Pharmaceutical Enhance CRPC Efficacy with Enzalutamide?

In an oral presentation of the phase 3 EORTC 1333/PEACE-3 trial, Enrique Gallardo, MD, medical oncologist at Parc Taulí University Hospital in Sabadell, Spain, discussed the efficacy of adding radium-223 to enzalutamide for the treatment of metastatic CRPC.²

Specifically, among 222 patients treated with the combination vs 224 treated with enzalutamide alone, the median OS was 38.21 months (95% CI, 33.08-44.75) vs 32.62 months (95% CI, 29.31-38.24) for an HR of 0.76 (95% CI, 0.60-0.96; P = .0096). Moreover, the respective 24- and 36-month rates were 71.1% (95% CI, 64.7%-76.6%) vs 67.7% (61.2%-73.4%) vs 54.2% (95% CI, 47.1%-60.6%) vs 47.4% (95% CI, 40.6%-54.0%).

Additionally, subgroup analyses revealed a reduced effect in patients 75 years or older, up to an HR of 1.01 from an HR of 0.66 in those who were younger. Moreover, those with prior docetaxel use or a higher World Health Organization (WHO) performance status experienced worse outcomes.

The median radiographic progression-free survival (PFS) was 19.19 months (95% CI, 16.92-24.57) vs 16.43 months (95% CI, 13.77-19.15) among the combination and control arms (HR, 0.71; 95% CI, 0.57-0.89). The respective 18- and 24-month rates were 52.9% (95% CI, 45.9%-59.4%) vs 44.5% (95% CI, 37.7%-51.0%) and 44.1% (95% CI, 37.2%-50.7%) vs 37.2% (95% CI, 30.7%-43.7%).

Regarding safety, treatment-emergent adverse effects (TEAEs) occurred in 100% of the combination arm vs 97.8% of the enzalutamide monotherapy arm. Treatment-related AEs (TRAEs) occurred at a rate of 83.0% vs 71.4%, with serious AEs occurring in 49.1% vs 32.6%, and serious TEAEs occurring in 10.6% vs 1.3% of each arm. Grade 3 or higher TEAEs were reported in 69.3% vs 57.6% of patients, with 28.9% vs 18.8% experiencing grade 3 or higher TRAEs.

Deaths resulting from AEs were observed in 4.6% vs 2.7% of the respective arms, although none were due to drug-related AEs. Treatment discontinuation of enzalutamide occurred in 5.5% of patients vs 5.4% in each arm, with a total of 3.2% of patients treated with radium-223 discontinuing the drug.

“With a median follow-up of nearly 5 years, enzalutamide plus 6 cycles of radium-223 demonstrated clinically meaningful OS benefit with a median gain of 5.6 months,” Gallardo explained. “The improvement in radiographic PFS is confirmed, and the safety profile shows a moderate but manageable increase in toxicity. Based on these results, this combination represents a first-line option for patients with metastatic CRPC with bone metastases, in conjunction with a bone-protecting agent as standard of care.”

What Did the Latest Readout of the KEYNOTE-B15 Trials Reveal About EV/Pembrolizumab in MIBC?

In an oral presentation of the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124) presented by Matthew D. Galsky, MD, professor of medicine and deputy director of the Mount Sinai Tisch Cancer Center, the combination of enfortumab vedotin-ejfv (EV; Padcev) delivered perioperatively plus pembrolizumab exhibited enhanced efficacy vs neoadjuvant cisplatin and gemcitabine for the treatment of patients with muscle-invasive bladder cancer (MIBC) eligible for cisplatin-containing regimens.³

Among patients treated with EV and pembrolizumab (n = 405) or cisplatin and gemcitabine (n = 403), the median event-free survival (EFS) was not reached (NR, 95% CI, NR-NR) vs 48.5 months (95% CI, 43.3-NR), respectively (HR, 0.53; 95% CI, 0.41-0.70; P <.0001), with respective 12- and 24-month rates of 86.0% vs 75.4% and 79.4% vs 66.2%. The median OS, which was a key secondary end point, across both arms was NR, with 12- and 24-month rates of 93.1% vs 89.6% and 86.9% vs 81.3%. (HR, 0.65; 95% CI, 0.48-0.89; P = .0029).

Regarding response, a pathologic complete response (pCR) was reached in 55.8% (95% CI, 50.8%-60.7%) of the investigational arm vs 32.5% (95% CI, 28.0%-37.3%) of the cisplatin/gemcitabine arm, for an estimated difference of 23.4% (95% CI, 16.7%-29.8%; P <.0001).

A total of 98.0% of patients experienced any-grade TEAEs in the EV/pembrolizumab arm vs 98.2% in the chemotherapy arm. The rate of grade 3 or higher or serious TEAEs were 75.7% and 63.3% in the investigational arm vs 67.2% vs 48.0% in the control arm. Moreover, TEAEs leading to death occurred in 4.2% vs 2.8% of the respective arms, and TRAEs leading to death occurred in 0.5% vs 0.3% of patients.

“This is a pivotal moment. For the first time in almost 25 years, since we first saw that cisplatin-based neoadjuvant therapy could improve outcomes in MIBC, a non-platinum regimen has now surpassed it,” Galsky stated in the presentation. “These results support neoadjuvant and adjuvant EV/pembrolizumab as a novel treatment option for patients with MIBC, regardless of their cisplatin eligibility.”

How Well is ¹⁷⁷Lu-PSMA-617 Tolerated in PSMA-Positive Metastatic HSPC?

Michael J. Morris, MD, prostate cancer section head in Genitourinary Oncology and Steven A. Greenberg Chair in Prostate Cancer Research at Memorial Sloan Kettering Cancer Center, delivered another oral session on a quality-of-life (QOL) analysis of the phase 3 PSMAddition trial evaluating ¹⁷⁷Lu-PSMA-617 for the treatment of patients with PSMA-positive metastatic HSPC.⁴

Therein, the higher median Functional Assessment of Cancer Therapy–Prostate (FACT-P; HR, 0.14; 95% CI, 0.98-1.33) and EQ-5D-5L utility scores (HR, 1.13; 95% CI, 0.97-1.31) were lower with ¹⁷⁷Lu-PSMA-617 vs ADT plus ARPI. Moreover, an HR of 1.02 (95% CI, 0.87-1.18) was observed in the BPI-SF pain intensity index.

Additionally, the median composite time to first symptomatic skeletal event (SSE) or death was NR in either arm (HR, 0.89; 95% CI, 0.62-1.26). Moreover, median time to first SSE excluding death was NR in both arms as well (HR, 0.87; 95% CI, 0.58-1.31).

“These data represent time to worsening [QOL] and pain…when the patient has the decline in [QOL], the patient is censored, and even if the patient’s [QOL] improves later in the study, you will not see that…We are presenting today the actual [QOL] data longitudinally, which is much more illuminating,” Morris explained in the presentation.

Does Lenvatinib Confer Synergistic Efficacy With Belzutifan in Advanced ccRCC?

In a readout of the phase 3 LITESPARK-011 trial (NCT04586231), Robert J. Motzer, MD, the Jack and Dorothy Byrne Chair in Clinical Oncology and section head of Kidney Cancer at Memorial Sloan Kettering Cancer Center, outlined the efficacy and safety findings with belzutifan and lenvatinib (Lenvima) vs cabozantinib (Cabometyx) among patients with advanced RCC.⁵

The PFS outcomes were significantly improved among patients treated with belzutifan/lenvatinib (n = 371) vs cabozantinib (n = 376). The median PFS in the respective arms was 14.8 months (95% CI, 11.2-16.6) vs 10.7 months (95% CI, 9.2-11.1), with 12- and 24-month rates of 55.0% vs 41.0% and 35.6% vs 19.1% (HR, 0.70; 95% CI, 0.59-0.84; P = .00007).

Moreover, the median OS was 34.9 months (95% CI, 27.5-NR) in the belzutifan/lenvatinib arm vs 27.6 months (95% CI, 24.0-31.4) in the cabozantinib arm. The 12- and 24-month rates were 79.7% vs 77.7% and 62.8% vs 55.4%, respectively (HR, 0.85; 95% CI, 0.68-1.05; P = .06075). Additionally, the overall response rate in the respective arms was 52.6% (95% CI, 47.3%-57.7%) and 40.2% (95% CI, 35.2%-45.3%), with 5.4% vs 1.1% of each arm achieving complete responses.

Any-grade AEs occurred in 99.7% vs 99.5% of the respective patient groups, with 84.1% vs 82.7% of each experiencing grade 3 or higher events. Serious AEs were reported in 51.6% vs 43.9%, respectively. Grade 3 or higher TRAEs occurred in 71.6% vs 65.8% of the respective arms, 26.5% vs 17.0% of which were serious. Of note, 0.5% vs 0.3% of TRAEs led to death in each arm.

“[T]here was statistically superior benefit in [PFS] for belzutifan plus lenvatinib compared with cabozantinib,” Motzer expressed in the presentation. “Belzutifan plus lenvatinib addresses an unmet clinical need and represents a potential new treatment option for patients with RCC that has progressed after anti–PD-(L)1 therapy.”

References

1. Choueiri TK, Motzer RJ, Karam JA, et al. Adjuvant pembrolizumab plus belzutifan versus pembrolizumab for clear cell renal cell carcinoma (ccRCC): the randomized phase 3 LITESPARK-022 study. J Clin Oncol. 2026;44(suppl 7):LBA418. doi:10.1200/JCO.2026.44.7_suppl.LBA418
2. Gallardo E, Tombal BF, Saad F, et al. Final overall survival results from the EORTC 1333/PEACE-3 trial: enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer. J Clin Oncol. 2026;44(suppl 7):15. doi:10.1200/JCO.2026.44.7_suppl.15
3. Galsky MD, Valderrama BP, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: randomized, open-label, phase 3 KEYNOTE-B15 study. J Clin Oncol. 2026;44(suppl 7):LBA630. doi:10.1200/JCO.2026.44.7_suppl.LBA630
4. Morris M, Gupta S, Tagawa ST, et al. Health-related quality of life, pain and symptomatic skeletal events in the phase 3 PSMAddition study of [177Lu]Lu-PSMA-617 combined with ADT and ARPI in patients with PSMA-positive mHSPC. J Clin Oncol. 2026;44(suppl 7):18. doi:10.1200/JCO.2026.44.7_suppl.18.
5. Motzer RJ, Park SH, McDermott RS, et al. Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti-PD-(L)1 therapy: open-label phase 3 LITESPARK-011 study. J Clin Oncol. 2026;44(suppl 7):417. doi:10.1200/JCO.2026.44.7_suppl417