Top ASCO GU 2026 Takeaways for Nurses and APPs

The 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium featured several high-impact studies detailing therapeutic advancements and patient-reported outcomes (PROs) across bladder, renal, and prostate cancers. For oncology nurses and advanced practice providers (APPs), these findings provide essential data on new treatment combinations, evolving safety profiles, and the long-term impact of therapy on patient quality of life (QOL).

KEYNOTE-B15/EV-304 Findings Show Neoadjuvant EV/Pembrolizumab Promise in MIBC

Data from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124) demonstrated that the combination of enfortumab vedotin-efjv (EV; Padcev) and pembrolizumab (Keytruda) significantly improved outcomes for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC).¹ In this study, 808 patients eligible for radical cystectomy and cisplatin-based chemotherapy were randomly assigned to receive either neoadjuvant EV/pembrolizumab or cisplatin plus gemcitabine.

The trial met its primary end point of event-free survival (EFS); EFS was not reached in the EV/pembrolizumab arm compared with 48.5 months in the control arm. Secondary end points also favored the experimental regimen. The pathological complete response rate was 55.8% vs 32.5%, respectively. At 24 months, the overall survival rate was 86.9% compared with 81.3%, respectively (HR, 0.65; 95% CI, 0.48-0.89; P = .0029).

From a nursing perspective, the safety profiles differed notably between the arms but were consistent with prior findings on the respective agents. Adverse events (AEs) of special interest for the combination included peripheral neuropathy and ocular disorders associated with EV, hypothyroidism and pneumonitis associated with pembrolizumab, and skin reactions associated with both.

LITESPARK-011 Data Favor Belzutifan/Lenvatinib in Clear Cell Renal Cell Carcinoma

In the second- and third-line settings for advanced clear cell renal cell carcinoma, the phase 3 LITESPARK-011 (NCT04586231) trial evaluated the HIF-2α inhibitor belzutifan (Welireg) in combination with lenvatinib (Lenvima) against cabozantinib (Cabometyx).² All 747 enrolled patients had experienced disease progression following immune checkpoint inhibitor (ICI) therapy.

Results showed a statistically significant improvement in progression-free survival (PFS) for the belzutifan/lenvatinib arm, with a median PFS of 14.8 months compared with 10.7 months with cabozantinib (HR, 0.70; 95% CI, 0.59-0.84; P = .00007). The objective response rate was also higher in the combination arm vs the cabozantinib arm, including 20 complete responses compared with 4 in the cabozantinib group. Further, the median duration of response was nearly doubled with the combination.

The most frequent treatment-emergent AEs for belzutifan/lenvatinib were anemia (69.2%), hypertension (58.9%), and diarrhea (52.7%); the cabozantinib arm saw frequent diarrhea (70.1%), hypertension (56.6%), and skin toxicities (51.2%). QOL was similar between the arms.

¹⁷⁷Lu-PSMA-617 Does Not Significantly Affect QOL and Pain in Metastatic Hormone-Sensitive Prostate Cancer

The phase 3 PSMAddition trial (NCT04720157) explored the impact of adding lutetium Lu 177 prostate-specific membrane antigen 617 (¹⁷⁷Lu-PSMA-617; Pluvicto) to androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) vs ADT/ARPI alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC).³ While previous data established a radiographic PFS benefit (HR, 0.72), new data on longitudinal PROs assessed the triplet’s impact on daily functioning.⁴

The analysis revealed that health-related QOL (HRQOL) and pain levels were largely maintained when ¹⁷⁷Lu-PSMA-617 was added to the standard doublet. Although there was a transient divergence in HRQOL scores during the 36-week period when patients were receiving doublet therapy alone, the scores reconverged with the control arm after the triplet phase was completed.

The time to the first symptomatic skeletal event or death was comparable between the arms. Pain control remained stable across both groups throughout the evaluable timeframe, suggesting that the addition of ¹⁷⁷Lu-PSMA-617 does not increase the symptomatic burden for patients with mHSPC.

Early QOL Dip Followed by Cognitive Decline, Pain With Durvalumab/Tremelimumab in Renal Cell Carcinoma

Findings from the phase 3 RAMPART trial (NCT03288532) demonstrated early declines in QOL for patients with resected RCC at risk of recurrence receiving adjuvant durvalumab (Imfinzi) plus tremelimumab (Imjudo), followed by later declines in cognitive function and pain, despite a 3-year median disease-free survival of 81% for the combination vs 73% for active monitoring (HR, 0.65; 95% CI, 0.45-0.93; P = .0094).

The QOL substudy found that patients receiving the combination therapy experienced significant early reductions in overall health, role functioning, and increased fatigue and insomnia by week 16. Many of these early deficits improved by month 15, but clinically meaningful declines in cognitive function and pain emerged at that later time point.

Safety data showed that 40% of patients in the combination arm experienced grade 3 or higher AEs, 32% discontinued treatment due to toxicities, and 36% required systemic corticosteroids. Common immune-related AEs included fatigue, colitis, pneumonitis, hypothyroidism, and dermatologic toxicity.

References

1. 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
2. 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):LBA417. doi:10.1200/JCO.2026.44.7_suppl.LBA417
3. Morris MJ, 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
4. Tagawa ST, Sartor O, Piulats JM, et al. LBA6 phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Ann Oncol. 2025;36(suppl 2):S1627-S1628. doi:10.1016/j.annonc.2025.09.101
5. Merrick S, Murphy L, Frangou E, et al. Patient-reported outcomes in resected renal cell carcinoma: active monitoring vs. durvalumab and tremelimumab in the RAMPART trial. J Clin Oncol. 2026;44(suppl 7):420. doi:10.1200/JCO.2026.44.7_suppl.420