(UroToday.com) The standard of care for eligible patients with muscle invasive bladder cancer (MIBC) is to receive neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC), which affords pathological tumor response assessment at surgery and also a survival advantage. Unfortunately, a subset of patients is not eligible for cisplatin-based chemotherapy due to extant heart failure, renal insufficiency, or neuropathy (peripheral and/or ototoxic). The authors highlight the unmet clinical need for effective systemic therapy for cisplatin-ineligible patients with MIBC. Given the success of pembrolizumab, an anti-PD1 immunotherapy agent, in both BCG-unresponsive non-muscle invasive bladder cancer and metastatic disease, the PURE-01 study was completed which demonstrated efficacy of pembrolizumab in the neoadjuvant setting.1
Here the authors sought to evaluate the subset of patients in PURE-01 who were cisplatin-ineligible, and compare those receiving neoadjuvant pembrolizumab and those who went immediately to radical cystectomy at the Moffitt Cancer Center. Endpoints of their evaluation included overall survival (OS) via Kaplan-Meier and comparison using Log-Rank functions. Cox-proportional hazards modeling was used to determine variable contribution to survival. To further eliminate confounding variables between the baseline clinicopathologic characteristics, those patients receiving immediate surgery were matched against cisplatin-ineligible patients from the PURE-01 trial using nearest neighbor propensity scoring technique. Patients were matched by pre-cystectomy ECOG status, GFR, age, sex, and clinical T stage. An exploratory analysis also matched patients by pathologic T stage.
Thirty-nine cisplatin-ineligible patients treated on the PURE-01 were identified against which 313 patients, also cisplatin-ineligible, received immediate RC. Baseline characteristics between the two groups, following nearest neighbor matching were well-balanced, as follows:
Higher rates of complete response on surgical pathology were observed in those patients receiving neoadjuvant pembrolizumab (pT0: 33% vs. 13%, p=0.03). Additionally, median OS was longer in the pembrolizumab group (NR v 21.0 months, p<0.01), a difference that persisted in both unmatched (top) and matched (bottom) cohorts.
The authors conclude this carefully completed study by stating that neoadjuvant pembrolizumab in cisplatin-ineligible patients with MIBC results in higher rates of downstaging and survival advantage, as compared to those patients proceeding to immediate RC without neoadjuvant treatment. Results of ongoing prospective randomized studies will hope to validate these findings and add non-platinum neoadjuvant treatment as a standard of care for cisplatin-ineligible patients with MIBC.
Presented by: Kyle M. Rose, MD, Moffitt Cancer Center, Tampa FL
Written by: Jones Nauseef, MD, PhD, Assistant Professor of Medicine within the Division of Hematology and Medical Oncology, Sandra and Edward Meyer Cancer Center, and Englander Institute for Precision Medicine Weill Cornell Medicine and Assistant Attending physician at NewYork-Presbyterian Hospital. @DrJonesNauseef on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.
References:
- Basile G, Bandini M, Gibb EA, Ross JS, Raggi D, Marandino L, Costa de Padua T, Crupi E, Colombo R, Colecchia M, Lucianò R, Nocera L, Moschini M, Briganti A, Montorsi F, Necchi A. Neoadjuvant Pembrolizumab and Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Cancer: 3-Year Median Follow-Up Update of PURE-01 Trial. Clin Cancer Res. 2022 Dec 1;28(23):5107-5114. doi: 10.1158/1078-0432.CCR-22-2158. PMID: 36190522.