A big step forwards in the management of muscle invasive bladder cancer in which platinum cannot be used has been taken in the KEYNOTE-905 study of perioperative antibody drug conjugate thereapy with
An interview with: Christof Vulsteke MD PhD, Medical Oncologist, Head of the Integrated Cancer Center Ghent, Belgium
BERLIN, Germany—Patients with muscle invasive bladder who were ineligible for cisplatin chemotherapy gained large, clinically meaningful and statistically significant benefits from treatment with the antibody drug conjugate enfortumab vedotin combined with pembrolizumab checkpoint inhibition in the phase three KEYNOTE-905 study.
At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Medical Oncologist Christof Vulsteke, Head of the Integrated Cancer Centre in Ghent, Belgium, reported marked improvements of event-free and overall survival among patients treated with the new combination, in comparison with those receiving standard radical cystectomy plus pelvic lymph node dissection. After his talk in Berlin he gave more details to Audio Journal of Oncology reporter Peter Goodwin:
Audio Journal of Oncology: Christof Vulsteke MD PhD; IN: “[GOODWIN] I am at the ESMO meeting in Berlin ……OUT: …Goodwin for the Audio Journal of Oncology, Goodbye 7:12 secs
ESMO 2025 ABSTRACT No. LBA2
“Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study”
Speaker: Christof Vulsteke (Gent, Belgium)
Authors:
Christof Vulsteke (Gent, Belgium) Hristos Kaimakliotis (Indianapolis, United States of America) Pongwut Danchaivijitr (Bangkok, Thailand) Maksym Y. Sabadash (Lviv, Ukraine) Alejo Rodriguez-Vida (Barcelona, Spain) Zhentao Zhang (Fort Wayne, United States of America) Vagiz Atduev (Nizhny Novgorod, Russian Federation) Yunus Emre Goger (Konya, Türkiye) Steffen Rausch (Tuebingen, Germany) Seok Ho Kang (Seoul, Republic of Korea) Yohann Loriot (Villejuif, France) Jens Bedke (Stuttgart, Germany) Matthew D. Galsky (New York, United States of America) Peter H. O’Donnell (Chicago, United States of America) Michael Mihm (Chicago, United States of America) Changting Meng (Groton, United States of America) David Huang (Rahway, United States of America) Chethan Ramamurthy (North Wales, United States of America) Blanca Homet Moreno (Madrid, Spain) Anders Ullén (Stockholm, Sweden)
Background
Radical cystectomy + pelvic lymph node dissection (RC + PLND) is the standard treatment for pts with MIBC who are cisplatin-ineligible. Periop therapy may improve outcomes in these pts.
Methods
The phase 3 KEYNOTE-905/EV-303 study (NCT03924895) evaluated efficacy and safety of periop EV + pembro and RC + PLND vs RC + PLND in adult pts with MIBC (T2-T4aN0M0 or T1-T4aN1M0) who were cisplatin-ineligible or declined cisplatin. Pts were randomized 1:1 to EV + pembro (3 cycles EV 1.25 mg/kg on d1 and d8 + pembro 200 mg on d1 Q3W, followed by RC + PLND, then 6 cycles EV + 14 cycles pembro) vs control (RC + PLND only). Study therapy continued until progression, unacceptable adverse events (AEs), withdrawal of consent, or completion of planned treatment. The primary endpoint was event-free survival (EFS) by blinded independent central review. Secondary endpoints were overall survival (OS; key), pathological complete response (pCR) rate (key), and safety.
Results
170 pts were randomized to EV + pembro and 174 pts to control. >80% of pts were cisplatin-ineligible per Galsky criteria. As of Jun 6, 2025, median follow-up time was 25.6 mo (range, 11.8–53.7). 149 pts (87.6%) in the EV + pembro arm and 156 (89.7%) in the control underwent surgery. EV + pembro significantly improved EFS (median not reached [NR] vs 15.7 mo; HR 0.40; 95% CI 0.28–0.57; P<.001), OS (NR vs 41.7 mo; HR 0.50; 95% CI 0.33–0.74; P<.001), and pCR rate (57.1% vs 8.6%; estimated difference 48.3%; 95% CI 39.5–56.5; P<.001) vs control. Treatment-emergent AEs occurred in 100% (gr ≥3, 71.3%) of pts in the EV + pembro arm and 64.8% (gr ≥3, 45.9%) in the control. Most frequent gr ≥3 AE of special interest (based on distinct prespecified lists for each drug) was severe skin reactions (grouped term; 11.4%) for pembro, and skin reactions (grouped term; 10.8%) for EV.
Conclusions
Adding periop EV + pembro to surgery significantly and meaningfully improved EFS, OS, and pCR rate in pts with MIBC who were predominantly cisplatin-ineligible. The safety profile of EV + pembro was manageable and consistent with prior reports. This is the first perioperakthrough regimen to improve outcomes vs RC + PLND in this setting and may be a new standard of care.
Clinical trial identification: NCT03924895.
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