Current SOC for pts w/ MIBC is neoadjuvant cis-based chemotherapy followed by radical cystectomy and pelvic lymph node dissection (RC+PLND). For pts who are cis-ineligible, SOC is RC+PLND alone but adjuvant therapy may be recommended. Due to high rates of recurrence in cis-ineligible pts, an urgent unmet need remains. Neoadjuvant EV showed promising antitumor activity in MIBC (pathological CR [pCR] of 36%, pathological downstaging [pDS] of 50%) in EV-103 Cohort H ( Petrylak 2022 ). Cohort L examines a perioperative approach.
Cohort L enrolled pts who are cis-ineligible w/ previously untreated MIBC (cT2-T4aN0M0 or cT1-T4aN1M0) who are medically fit for and agree to undergo curative intent RC+PLND within 12 wks. Pts received 3 cycles of neoadjuvant EV (1.25mg/kg) on Days 1 and 8 of each 3-week cycle followed by RC+PLND and then 6 cycles of adjuvant EV (1.25 mg/kg) on Days 1 and 8 of every 3 week cycle starting 8 weeks post-RC. Primary endpoint is pathological CR (pCR) per central pathology review; secondary endpoints include pathological downstaging (pDS) rate per central pathology review, safety and tolerability. Here we present initial results from the neoadjuvant/RC+PLND phase + 30 days post surgery.
52 pts were enrolled. 51 pts were treated w/ EV in the neoadjuvant phase w/ a median of 3 cycles; 42 pts (82.4%) completed RC+PLND. One pt achieved clinical CR and elected not to undergo RC+PLND and was excluded from pCR and pDS analyses; 17/50 (34.0%) pts had a pCR. pDS was seen in 21/50 (42.0%) pts. In the neoadjuvant/RC+PLND phase, of 51 treated pts most common EV-related TEAEs were fatigue (52.9%), rash maculo-papular (31.4%), and nausea (29.4%). 39.2% of pts had an EV-related TEAE ≥ grade 3; 31.4% pf pts had a RC-related TEAE ≥ grade 3. No surgeries were delayed due to EV-related TEAEs. One pt (2.0%) experienced an EV-related death (Stevens-Johnson syndrome) before surgery.
EV continues to show promising activity and was tolerable in cis-ineligible pts w/ MIBC in this ongoing trial. Both the efficacy and safety profiles were consistent with previously reported data from Cohort H. These data support the ongoing phase 3 trials evaluating EV + pembrolizumab in MIBC.
EudraCT 2018-001527-39; Release Date: Amendment 11, 15-Feb-2023.