News|Articles|February 27, 2026

Padcev Plus Keytruda Improves Survival in Muscle-Invasive Bladder Cancer

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Key Takeaways

Event-free survival improved with EV/pembro: median not reached vs 48.5 months, and 24‑month EFS 79.4% vs 66.2% with cisplatin/gemcitabine.
Overall survival separated early (24‑month 86.9% vs 81.3%), alongside higher pathologic complete response (55.8% vs 32.5%; 64.4% vs 36.3% post-cystectomy).
Consistency across PD‑L1 status, clinical stage, and geography supports broad activity independent of biomarker stratification in cisplatin-eligible localized MIBC.
Study design randomized 808 patients to 4 neoadjuvant cycles then cystectomy; the experimental arm added adjuvant EV (5 cycles) plus pembrolizumab (13 cycles).
Grade ≥3 TEAEs were 75.7% vs 67.2%, with more pruritus/diarrhea/rash/alopecia on EV/pembro and more cytopenias/nausea on chemotherapy; deaths were rare.

Padcev plus Keytruda before and after surgery helped more bladder cancer patients live longer and remain cancer-free than standard chemotherapy.

Neoadjuvant and adjuvant Padcev (enfortumab vedotin) and Keytruda (pembrolizumab) significantly and meaningfully improved event-free survival, overall survival and pathological complete response versus neoadjuvant cisplatin plus gemcitabine in patients with muscle-invasive bladder cancer who are eligible for cisplatin-containing therapy and radical cystectomy. Results were delivered during the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Event-free survival, the primary end point, was longer for patients who received Padcev plus Keytruda compared with cisplatin and gemcitabine. The median event-free survival was not reached in the Padcev plus Keytruda arm versus 48.5 months for the cisplatin and gemcitabine arm. At 24 months the event-free survival rate was 79.4% for Padcev plus Keytruda versus 66.2% for cisplatin and gemcitabine.

The effect on event-free survival was generally consistent across key study subgroups, regardless of programmed death ligand 1 status, clinical stage and geographic region.

Overall survival was also longer with Padcev plus Keytruda versus cisplatin and gemcitabine. The median overall survival was not reached in either arm. At 24 months the overall survival rate was 86.9% with Padcev plus Keytruda versus 81.3% with cisplatin and gemcitabine.

Pathological complete response favored the Padcev plus Keytruda arm at 55.8% versus 32.5% with cisplatin and gemcitabine. Among patients who underwent cystectomy the pathological complete response rate was 64.4% with Padcev plus Keytruda versus 36.3% with cisplatin and gemcitabine.

“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 muscle-invasive bladder cancer, a non-platinum regimen has now surpassed it,” said Dr. Matthew Galsky, professor of medicine and deputy director of the Mount Sinai Tisch Cancer Center in New York.

Treatment duration was longer in the Padcev plus Keytruda arm. Patients received a median of 10.2 months of treatment versus 3.5 months with cisplatin and gemcitabine. Among those starting neoadjuvant therapy the median number of cycles was 4 in both arms. In the adjuvant phase patients received a median of 5 cycles of Padcev and 13 cycles of Keytruda.

The median age in both arms was 66 years and most patients had an Eastern Cooperative Oncology Group performance status of 0. Approximately 80% had clinical T3 disease or higher by central assessment and approximately 70% had clinical T2 disease by local assessment.

Grade 3 or higher treatment-emergent side effects occurred in 75.7% of patients in the Padcev plus Keytruda arm and 67.2% in the cisplatin and gemcitabine arm. Treatment-emergent side effects leading to death occurred in 2 patients in the experimental arm and in 1 patient in the cisplatin and gemcitabine arm.

The safety profiles were consistent with prior observations. Patients who received Padcev plus Keytruda experienced more pruritus, diarrhea, alopecia and rash. Patients who received cisplatin and gemcitabine experienced more neutropenia, thrombocytopenia, anemia and nausea. Surgical-phase side effects were similar between arms.

Side effects of special interest with Padcev included skin reactions, peripheral neuropathy and ocular disorders. With Keytruda the most common were skin reactions, hypothyroidism and pneumonitis.
Background
The study enrolled patients with clinically localized muscle-invasive urothelial cancer of the bladder who were eligible for cisplatin-based chemotherapy and radical cystectomy. A total of 808 patients were randomly assigned between May 2021 and December 2023.
Patients received enfortumab vedotin plus pembrolizumab (405 patients) versus cisplatin and gemcitabine (403 patients) for 4 cycles followed by radical cystectomy. Patients in the Padcev plus Keytruda arm then received adjuvant Padcev for 5 cycles and Keytruda for 13 cycles. Patients in the control arm were observed after cystectomy.

“These results support neoadjuvant and adjuvant enfortumab vedotin and pembrolizumab as a novel treatment option for patients with muscle-invasive bladder cancer regardless of their cisplatin eligibility,” Galsky concluded.

References

“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,” by Dr. Matthew Galsky, et al. Journal of Clinical Oncology.

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