Enfortumab vedotin plus pembrolizumab extends survival in MIBC

In patients with muscle-invasive bladder cancer (MIBC) eligible for cisplatin-based chemotherapy, neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab elicits improvements in event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) rate relative to neoadjuvant gemcitabine plus cisplatin, according to the phase III KEYNOTE-B15 study.

Moreover, the safety profile of neoadjuvant and adjuvant EV plus pembrolizumab is consistent with previous results with this combination.

“The KEYNOTE-B15 study, coupled with the recently reported results from the KEYNOTE-905 study, supports neoadjuvant and adjuvant EV plus pembrolizumab as a treatment option for patients with MIBC, regardless of cisplatin-eligibility,” said lead author and presenter Dr Matthew D. Galsky, Mount Sinai Tisch Cancer Center, New York, New York, US.

A total of 808 patients with clinical stage T2-T4aN0M0 or T1-T4aN1M0 MIBC who were eligible for cisplatin-based chemotherapy and radical cystectomy plus pelvic lymph node dissection (RC plus PLND) were included in the KEYNOTE-B15 study.

Of the participants, 405 were randomized to receive 4 cycles neoadjuvant EV 1.25 mg/kg intravenously (IV) on days 1 and 8 plus pembrolizumab 200 mg IV on day 1 Q3W, followed by RC plus PLND, and adjuvant 5 cycles EV plus 13 cycles pembrolizumab, and 403 to 4 cycles neoadjuvant gemcitabine 1,000 mg/m² on days 1 and 8 plus cisplatin 70 mg/m² on day 1 Q3W, followed by RC plus PLND.

EFS by blinded independent central review was the primary endpoint, and secondary endpoints were pCR rate by blinded central pathological review, OS, and safety. Adverse events (AEs) of special interest were based on distinct prespecified lists for each drug.

The median time from randomization to data cutoff (27 October 2025) was 33.6 months. Baseline characteristics between treatment groups were generally balanced. [ASCO GU 2026, abstract LBA630]

Patients in the EV plus pembrolizumab arm, compared with those in the cisplatin plus gemcitabine arm, showed significant improvements in EFS (median not reached [NR] vs 48.5 months; 24-month estimated EFS rate: 79.4 percent vs 66.2 percent; hazard ratio [HR], 0.53, 95 percent confidence interval [CI], 0.41‒0.70; p<0.0001).

Secondary outcomes

Likewise, OS (median NR vs NR; 24-month estimated OS rate: 86.9 percent vs 81.3 percent; HR, 0.65, 95 percent CI, 0.48‒0.89; p=0.0029) and pCR rate (55.8 percent vs 32.5 percent; estimated difference, 23.4 percent, 95 percent CI, 0.16.7‒29.8; p<0.001) were significantly better with EV plus pembrolizumab than with cisplatin plus gemcitabine.

The median total duration of therapy was 10.2 months in the EV plus pembrolizumab group and 3.5 months in the cisplatin plus gemcitabine group.

Notably, grade ≥3 treatment-emergent AEs (TEAE) were higher in patients treated with EV plus pembrolizumab than those who received cisplatin plus gemcitabine (75.7 percent vs 67.2 percent). The most common TEAEs were pruritus (46.2 percent) in the EV plus pembrolizumab arm and anaemia (56.3 percent) in the cisplatin and gemcitabine arm.

“EV plus pembrolizumab represents the first antibody drug conjugate plus immune checkpoint inhibitor combination to improve outcomes vs cisplatin-based chemotherapy in patients with MIBC eligible for curative intent surgery and cisplatin-containing therapy,” Galsky said.