Pembrolizumab with Chemoradiation as Treatment for Muscle-invasive Bladder Cancer: Analysis of Safety and Efficacy of the PCR-MIB Phase 2 Clinical Trial (ANZUP 1502).

Autor: Weickhardt A; Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Melbourne, Australia. Electronic address: andrew.weickhardt@austin.org.au., Foroudi F; Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Melbourne, Australia., Lawrentschuk N; Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Australia., Xie J; Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Australia., Sidhom M; Liverpool Hospital, Sydney, Australia., Pal A; Liverpool Hospital, Sydney, Australia., Grimison P; Chris O'Brien Lifehouse, Sydney, Australia., Zhang A; Chris O'Brien Lifehouse, Sydney, Australia., Ng S; Sir Charles Gairdner Hospital, Perth, Australia., Tang C; Sir Charles Gairdner Hospital, Perth, Australia., Hovey E; Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Sydney, Australia., Chen C; Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Sydney, Australia., Hruby G; Royal North Shore Hospital, Sydney, Australia., Guminski A; Royal North Shore Hospital, Sydney, Australia., McJannett M; Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, Australia., Conduit C; Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Australia; Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, Australia., Tran B; Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Australia., Davis ID; Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, Australia; Monash University, Melbourne, Australia; Eastern Health, Melbourne, Australia., Hayne D; Fiona Stanley Hospital, Perth, Australia.
Jazyk: angličtina
Zdroj: European urology oncology [Eur Urol Oncol] 2024 Jun; Vol. 7 (3), pp. 469-477. Date of Electronic Publication: 2023 Oct 07.
DOI: 10.1016/j.euo.2023.09.011
Abstrakt: Background: Radiation may improve the efficacy of immune checkpoint inhibition. This study investigates the combination of pembrolizumab and chemoradiation (CRT) for muscle-invasive bladder cancer (MIBC).
Objective: To assess the feasibility and safety of pembrolizumab combined with CRT for MIBC.
Design, Setting, and Participants: A single-arm phase 2 trial was performed with 28 participants having cT2-T4aN0M0 MIBC (Eastern Cooperative Oncology Group performance status 0-1; estimated glomerular filtration rate ≥40 ml/min; no contraindications to pembrolizumab) suitable for CRT.
Intervention: Whole bladder radiation therapy (RT; 64 Gy in 32 daily fractions, over 6.5 wk, combined with cisplatin (35 mg/m 2 intravenously [IV] weekly, six doses) and pembrolizumab (200 mg IV q3 weeks, seven doses), both starting with RT. Surveillance cystoscopy/biopsy and computerised tomography scans performed 12 and 24 wk after CRT.
Outcome Measurements and Statistical Analysis: The primary endpoint was feasibility, determined by a prespecified satisfactory low rate of grade 3 or worse nonurinary toxicity or completion of planned CRT according to defined parameters. Secondary endpoints were complete cystoscopic response, locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and overall survival (OS).
Results and Limitations: Twenty-eight patients were enrolled with a 31-mo median follow-up. Six had Grade >3 nonurinary adverse events during/within 12 wk after treatment; three had more than one cisplatin dose reduction. The 24-wk post-CRT complete response (CR) rate was 88%. Eight patients developed metastatic disease, and three had nonmetastatic progression. The DMFS at 2 yr is 78% (95% confidence interval [CI] 54-90%), with LRPFS at 2 yr of 87% (95% CI 64-96%) and median OS of 39 mo (95% CI 17.1-not evaluable). Limitations are the single-arm design and sample size.
Conclusions: Combining pembrolizumab with CRT for MIBC was feasible, with manageable toxicity and promising CR rates.
Patient Summary: Immunotherapy treats nonmetastatic/metastatic bladder cancer effectively. We combined pembrolizumab with chemotherapy and radiation to assess its safety and impact on treatment delivery. The combination was feasible with encouraging early activity. Further larger trials are warranted.
(Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: