(UroToday.com) The 2026 GU ASCO annual meeting featured a urothelial carcinoma session and a presentation by Dr. Brigida Maiorano discussing the perioperative enfortumab vedotin + pembrolizumab versus neoadjuvant pembrolizumab in cisplatin-ineligible patients with muscle-invasive bladder cancer.
Cisplatin-based chemotherapy is the standard neoadjuvant therapy for patients with muscle-invasive bladder cancer. However, a significant proportion of patients are ineligible for/refuse chemotherapy, requiring alternative perioperative strategies. PURE-01 tested neoadjuvant pembrolizumab monotherapy before radical cystectomy in patients with cT2–T4N0M0 muscle–invasive bladder cancer, without an adjuvant period.1 KEYNOTE-905/EV-303 is a randomized, phase III study testing perioperative enfortumab vedotin + pembrolizumab, followed by radical cystectomy and adjuvant enfortumab vedotin + pembrolizumab for 6 cycles, then pembrolizumab alone for an additional 6 cycles, versus radical cystectomy alone. EV-303 included a third arm of pembrolizumab monotherapy, which was stopped in 2022. The contribution of both therapeutic components in the enfortumab vedotin + pembrolizumab regimen and the neoadjuvant versus adjuvant part remains uncertain.
An indirect comparison of trials was performed using individual patient data reconstructed from Kaplan–Meier curves. The endpoints were event-free survival and overall survival since initiation of treatment. Individual patient-level data were retrieved using a graphical reconstructive algorithm and merged into a single dataset including two treatment groups. Event-free survival was estimated with Kaplan–Meier curves and compared with the log-rank test and the Cox proportional hazards model. Landmark estimates at 12 and 24 months, and median values were calculated.
A total of 170 patients from KEYNOTE-905/EV-303 (enfortumab vedotin + pembrolizumab arm) and 155 from PURE-01 were included. Baseline staging was cT2 in 17.6% of patients in the enfortumab vedotin + pembrolizumab group and 48.4% in the pembrolizumab group. Additionally, there were 78.2% and 51.6% of patients with cT3/T4 disease, respectively, and 4.1% and 0% for clinical N1 stage, respectively:
Pathologic complete response was higher in the enfortumab vedotin + pembrolizumab group than in the pembrolizumab group: 57.1% versus 39.5%. The individual patient data -based Cox analysis showed no significant difference in event-free survival (HR 0.75, 95% CI 0.49–1.14; p = 0.181):
Additionally, the medians were not reached in both arms:
Dr. Maiorano concluded her presentation discussing the perioperative enfortumab vedotin + pembrolizumab versus neoadjuvant pembrolizumab in cisplatin-ineligible patients with muscle-invasive bladder cancer with the following take-home points:
- An indirect individual patient data-based comparison between enfortumab vedotin + pembrolizumab and pembrolizumab did not result in statistically significant differences in event-free survival
- These results emphasize the importance of conducting clinical trials aimed at discriminating the contribution of components that remain uncertain, representing a critical need
- Limitations include the retrospective design, indirect comparison, and patient and geographical heterogeneity
Presented by: Brigida A. Maiorano, MD, IRCCS Ospedale San Raffaele, Milan, Italy
Reference:
- Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol 2018 Dec 1;36(34):3353-3360.