Perioperative EV plus pembro tied to better outcomes in patients with MIBC

Perioperative treatment with enfortumab vedotin and pembrolizumab (EV plus pembro) significantly improves event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) rates in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy, according to the KEYNOTE-905 trial presented at EAU26.

This phase III trial involved 344 patients with MIBC who were randomized to receive IV EV 1.25 mg/kg on days 1 and 8 Q3W plus IV pembro 200 mg Q3W for three cycles in addition to surgery (RC* and PLND**) and EV for six cycles plus pembro for 14 cycles (EV plus pembro arm; n=170) or surgery alone (control arm; n=174). [EAU26, abstract A0875]

At 2 years, the median EFS and OS were not reached in the EV plus pembro arm compared with 15.7 and 41.7 months, respectively, in the control arm (hazard ratios [HRs], 0.40; p<0.0001 [EFS] and 0.50; p=0.0002 [OS]).

In turn, the 2-year EFS and OS rates were higher among patients treated with EV plus pembro compared with surgery alone (74.7 percent vs 39.4 percent [EFS] and 79.7 percent vs 63.1 percent [OS]).

The disease-free survival (DFS) rate was also higher in the combination arm than in the control arm at 2 years (62 percent vs 49.6 percent), with median DFS not reached vs 23.6 months.

As assessed by the Central Pathology Review, patients treated with EV plus pembro demonstrated a significantly higher pCR rate compared with those who underwent surgery alone (57.1 percent vs 8.6 percent), with an estimated difference of 48.3 percentage points (one-sided p<0.000001).

Additionally, pathological downstaging, defined as a tumour stage <pT2N0, was observed in 65.9 percent of patients in the combination arm compared with 12.6 percent in the control arm, with an estimated treatment difference of 53.1 percentage points.

Safety

Grade ≥3 treatment-emergent adverse events (TEAEs) occurred more frequently in the combination arm than in the control arm (71.3 percent vs 45.9 percent), as did serious TEAEs (58.1 percent vs 40.9 percent) and TEAEs that led to death (7.8 percent vs 5.7 percent).

The most common TEAE reported with EV plus pembro in the neoadjuvant and adjuvant phases was pruritus (35.3 percent and 28 percent, respectively), whereas urinary tract infection (12.9 percent) was observed in the control group during the surgical phase.

The safety profile of neoadjuvant and adjuvant EV plus pembro was consistent with prior studies that included patients with locally advanced or metastatic urothelial carcinoma, with no new safety signals observed. [NEJM 2026;doi:10.1056/NEJMoa2511674]

“Overall, these results suggest that perioperative EV plus pembro can be integrated into uro-oncology decision making and may now represent a new standard of care,” said study author Dr Neal Shore from Carolina Urologic Research Center in Myrtle Beach, South Carolina, US.