PrECOG PrE0807: A Phase 1b Feasibility Trial of Neoadjuvant Nivolumab Without and with Lirilumab in Patients with Muscle-invasive Bladder Cancer Ineligible for or Refusing Cisplatin-based Neoadjuvant Chemotherapy.

Autor: Grivas P; Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA. Electronic address: pgrivas@uw.edu., Koshkin VS; Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, USA., Chu X; Dana-Farber Cancer Institute, Boston, MA, USA., Cole S; University of Texas Southwestern Medical Center, Dallas, TX, USA., Jain RK; H Lee Moffitt Cancer Center, Tampa, FL, USA., Dreicer R; University of Virginia Cancer Center, Charlottesville, VA, USA., Cetnar JP; Oregon Health and Science University, Portland, OR, USA., Sundi D; Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH, USA., Gartrell BA; Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Galsky MD; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Woo B; Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA., Li-Ning-Tapia E; University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hahn NM; Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Carducci MA; Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jazyk: angličtina
Zdroj: European urology oncology [Eur Urol Oncol] 2024 Aug; Vol. 7 (4), pp. 914-922. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1016/j.euo.2023.11.022
Abstrakt: Background and Objective: Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) improves overall survival (OS) in muscle-invasive bladder cancer (MIBC). However, many patients are cisplatin ineligible; therefore, new treatment options are needed. Nivolumab without/with lirilumab prior to RC was investigated in cisplatin-ineligible patients in this phase 1b trial (NCT03532451) to determine its safety/feasibility.
Methods: Patients with localized MIBC received two doses of nivolumab (480 mg) alone (cohort 1) or with lirilumab (240 mg; cohort 2) prior to RC. Cohorts were enrolled sequentially. The key eligibility criteria were cT2-4aN0-1M0 stage and cisplatin ineligibility/refusal. The primary endpoint was the rate of grade (G) ≥3 treatment-related adverse events (TRAEs) as per Common Terminology Criteria for Adverse Events version 5.0. The key secondary endpoints included the proportion of patients who underwent RC >6 wk after the last dose, CD8+ T-cell density change between pretreatment transurethral resection of bladder tumor (TURBT) and post-treatment RC, ypT0N0, Key Findings and Limitations: Among 43 patients enrolled (n = 13, cohort 1; n = 30, cohort 2), 13 and 29 completed intended neoadjuvant therapy, respectively, in cohorts 1 and 2, and 41 underwent RC. The median time from the last dose to RC was 4 wk. The G3 TRAEs occurred in 0% (90% confidence interval [CI] 0-21%) of patients in cohort 1 and 7% (90% CI 1-20%) in cohort 2; all these TRAEs resolved and no G4/5 TRAEs occurred. No patient had delayed RC for >6 wk. In cohorts 1 and 2, ypT0N0 rates for patients with MIBC and RC were 17% and 21%, Conclusions and Clinical Implications: Neoadjuvant nivolumab-based immunotherapy was safe, feasible, and well tolerated in cisplatin-ineligible patients with MIBC. Although ypT0N0 rates were lower than expected, 2-yr survival rates seem to be comparable with those of other neoadjuvant immunotherapy trials. Nivolumab is being evaluated in the CA-017-078 trial (NCT03661320).
Patient Summary: For patients with muscle-invasive bladder cancer unable to receive cisplatin-based chemotherapy, treatment with nivolumab without and with lirilumab prior to radical cystectomy was safe, feasible, and well tolerated. Nivolumab-based immunotherapy showed lower pathologic response rates than but similar survival rates to other neoadjuvant immunotherapy trials.
(Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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