(UroToday.com) The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting was host to a kidney and bladder cancers poster session. Dr. Nabil Adra presented an analysis of clinically relevant subgroups from the KEYNOTE-905 trial of perioperative (neoadjuvant + adjuvant) enfortumab vedotin + pembrolizumab (EV + pembro) in cisplatin-ineligible, muscle-invasive bladder cancer (MIBC) patients.
Patients with cisplatin-ineligible MIBC represent a major unmet clinical need. Although cisplatin-based neoadjuvant chemotherapy has been the standard perioperative approach for eligible patients, many individuals are unable to receive cisplatin because of renal dysfunction, poor performance status, neuropathy, or other comorbidities. EV + pembro has demonstrated substantial activity in advanced urothelial carcinoma, and results from the KEYNOTE-905/EV-303 trial have previously demonstrated significant improvements in event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) versus radical cystectomy with pelvic lymph node dissection (RC + PLND) alone in cisplatin-ineligible or cisplatin-declining patients.1 This analysis evaluated whether these benefits were maintained across clinically relevant patient subgroups.
KEYNOTE-905/EV-303 (NCT03924895) enrolled adults with:
- cT2-T4aN0M0 or T1-T4aN1M0 MIBC by central review
- Cisplatin-ineligible disease or declining cisplatin therapy
Patients were randomized 1:1 to:
- Neoadjuvant and adjuvant EV + pembro plus RC + PLND
- RC + PLND alone
Endpoints evaluated in clinically relevant subgroups included:
- BICR-assessed EFS
- OS
- pCR (pT0N0) by central review
The relevant subgroups of interest were as follows:
- Age: ≥65 to <75 years versus ≥75 years
- ECOG performance status: 0–1 versus 2
- Cisplatin eligibility status: ineligible versus declined
- Baseline clinical stage:
- T2N0
- T3-T4aN0
- T1-4aN1
These analyses were exploratory in nature, and no formal hypothesis testing was performed.
A total of 170 patients were assigned to EV + pembro, and 174 were assigned to the control group. The median follow-up was 25.6 months at the June 6, 2025 data cutoff.
Treatment effects with EV + pembrolizumab were generally consistent across baseline stage subgroups, although most enrolled patients had T3–T4aN0 disease (133 versus 132 patients), whereas fewer had T2N0 (30 versus 32) or node-positive T1–4aN1 disease (7 versus 10). Outcomes by stage were as follows:
- In the T2N0 cohort, the median EFS was not reached in either arm, though EV + pembrolizumab was associated with a marked improvement in EFS (HR 0.26, 95% CI 0.08–0.80) and substantially higher pCR rates (60.0% versus 18.8%).
- Among patients with T3–T4aN0 disease, EV + pembrolizumab improved both EFS (HR 0.43, 95% CI 0.29–0.63) and OS (HR 0.54, 95% CI 0.35–0.82), with median EFS and OS not reached compared to 17.2 months and 41.7 months in the control arm, respectively. pCR rates in this subgroup were also notably higher with EV + pembrolizumab (57.1% versus 6.8%).
- In the smaller T1–4aN1 cohort, median EFS was prolonged from 7.2 to 36.7 months (HR 0.35, 95% CI 0.09–1.40), with pCR achieved in 42.9% of EV + pembrolizumab-treated patients versus none in the control arm, although OS data for both the T2N0 and node-positive cohorts remain immature because of limited event numbers.
Benefits were similarly observed across age and performance status subgroups:
- Among patients aged 65 to <75 years, EV + pembrolizumab improved EFS (HR 0.41) and OS (HR 0.49), with pCR rates of 54.0% versus 9.1%, while patients aged ≥75 years experienced comparable improvements in EFS (HR 0.50) and numerically favorable OS outcomes (HR 0.63), alongside pCR rates of 53.8% versus 7.4%.
- Significant benefits were observed among patients with ECOG PS 2, in whom EV + pembrolizumab was associated with marked improvements in EFS (HR 0.19) and OS (HR 0.17), with pCR rates of 81% compared to 7.7% in the control arm. Similarly, among cisplatin-ineligible patients, EV + pembrolizumab improved EFS (HR 0.37) and OS (HR 0.46), with pCR rates of 54.9% versus 8.6%.
The investigators concluded that neoadjuvant and adjuvant EV + pembro for MIBC patients undergoing a RC + PLND demonstrated efficacy benefit across clinically relevant subgroups, consistent with findings in the intention-to-treat population. These data further reinforce EV + pembro as a potential new perioperative standard for cisplatin-ineligible MIBC, including older patients, those with ECOG PS 2, and patients with more advanced local disease. Particularly notable were the high pCR rates and durable EFS improvements observed across essentially all evaluated subgroups, supporting broad applicability of this regimen in a population historically lacking effective perioperative treatment options.
Presented by: Nabil Adra, MD, Associate Professor of Clinical Medicine, Indiana University Health, Indianapolis, IN, USA
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center, Tucson, AZ – @rksayyid on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026
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