Clinical Summary:

• Design/Population: The phase 3 KEYNOTE-905 trial evaluated perioperative enfortumab vedotin plus pembrolizumab (neoadjuvant followed by adjuvant therapy) versus radical cystectomy alone in patients with muscle-invasive bladder cancer who were cisplatin-ineligible or declined cisplatin. The reported analysis focused on health-related quality of life (HRQoL), with the primary endpoint assessing change from baseline to week 18 and additional longitudinal HRQoL assessments throughout treatment.
• Key Outcomes: Overall HRQoL was generally preserved in both treatment arms, with no major differences between baseline and week 18. Expected declines in bowel function and sexual function occurred after radical cystectomy, reaching a nadir approximately 9 weeks after surgery before improving over time. Importantly, the addition of enfortumab vedotin plus pembrolizumab did not result in additional deterioration in overall or cystectomy-specific HRQoL.
• Clinical Relevance: These findings complement the previously reported efficacy results supporting perioperative enfortumab vedotin plus pembrolizumab as the standard of care for cisplatin-ineligible muscle-invasive bladder cancer. The preservation of HRQoL provides reassurance that the addition of systemic therapy does not substantially worsen patient-reported outcomes beyond the expected effects of cystectomy.

Peter O’Donnell, MD, of the University of Chicago, discusses health-related quality-of-life (HRQoL) findings from the phase 3 KEYNOTE-905 study evaluating perioperative enfortumab vedotin plus pembrolizumab in patients with muscle-invasive bladder cancer who were cisplatin-ineligible or declined cisplatin. The trial established perioperative enfortumab vedotin plus pembrolizumab as a new standard of care, and the current analysis examined both general and cystectomy-specific HRQoL using longitudinal patient-reported outcome measures.

Results showed that HRQoL was generally maintained with perioperative enfortumab vedotin plus pembrolizumab and was comparable with cystectomy alone. Although expected postoperative declines in bowel and sexual function were observed after radical cystectomy, these changes reached their greatest severity approximately 9 weeks after surgery and generally improved over time. Importantly, the addition of enfortumab vedotin plus pembrolizumab did not result in meaningful additional deterioration in overall or cystectomy-specific HRQoL, supporting the favorable benefit-risk profile of this perioperative treatment approach.

Dr O’Donnell presented these findings at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

Hi, I’m Dr. Peter O’Donnell at the University of Chicago, and I was really excited at this meeting, ASCO 2026, to present the health-related quality-of-life findings from KEYNOTE-905.

As everybody remembers, KEYNOTE-905 was the paradigm-shifting trial that looked at the use of perioperative, or neoadjuvant plus adjuvant, enfortumab vedotin plus pembrolizumab in patients with muscle-invasive bladder cancer who were cisplatin-ineligible or who declined cisplatin.

In that trial, everybody remembers that there was a neoadjuvant portion of EV plus pembro, then radical cystectomy, and then patients received an adjuvant portion of EV plus pembro. What we really layered onto those efficacy data, which are well known and which have resulted in that regimen now becoming the standard of care for muscle-invasive bladder cancer patients who are cisplatin-ineligible, were the health-related quality-of-life data.

We used several different metrics that looked at general health-related quality of life and bladder cancer/cystectomy-specific health-related quality of life in patients in both arms of the trial. The primary endpoint was looking at change in health-related quality-of-life assessments from baseline to week 18, but we also looked at subscales that involved longitudinal data over the entire course of patients being observed through these regimens.

What we saw was that health-related quality of life was generally preserved in patients in both arms, the EV plus pembro arm and the cystectomy-alone arm. We didn’t see major decrements in health-related quality of life comparing baseline to week 18.

We did see some differences right after surgery in patients in both arms, and these were functional changes that would be well known and well associated with cystectomy, including changes in bowel habits and decreases in sexual function. These tended to reach their nadir around the 9-week point after surgery. So that first assessment after radical cystectomy is where we saw patients experience some of these decreases.

However, patients generally regained function in most domains over time after cystectomy. So, in some ways, the trial really showed us in a formal way what we already know about cystectomy having a functional impact on patients.

Patients who received the addition of EV plus pembro did not show additional decrements in health-related quality of life from receiving those systemic drugs.

I think these are really important health-related quality-of-life data that complement the exciting efficacy data that have now led to EV plus pembro as a perioperative regimen becoming the new standard of care. We can now complement those efficacy findings by knowing that, according to these health-related quality-of-life metrics, we don’t see major decrements in patients’ overall health-related quality of life or cystectomy-specific health-related quality of life with the addition of EV plus pembro.

Source:

O’Donnell PH, Adra N, Alimohamed N, Ku JH, Danchaivijitr P, Ullén A, et al. Health-related quality of life (HRQoL) with neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin ineligible: Phase 3 KEYNOTE-905 study. Presented at the ASCO Annual Meeting. 2026.