Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance.

Bladder cancer Clinical trial Immunotherapy Maintenance Phase 3 Randomized Urothelial carcinoma

Journal

European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719

Informations de publication

Date de publication:
13 Sep 2023
Historique:
received: 02 08 2022
revised: 28 06 2023
accepted: 01 08 2023
medline: 16 9 2023
pubmed: 16 9 2023
entrez: 15 9 2023
Statut: aheadofprint

Résumé

In the JAVELIN Bladder 100 phase 3 trial, avelumab first-line maintenance + best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (advanced UC) without progression after first-line platinum-based chemotherapy. To report post hoc analyses of subgroups defined by the duration of first-line chemotherapy and interval before maintenance. Patients with advanced UC without progression after four to six cycles of platinum-based chemotherapy and a 4-10-wk interval after chemotherapy (n = 700) were randomized to receive avelumab + BSC or BSC alone. Subgroups were defined by duration (quartile [Q]) and estimated number of cycles of chemotherapy, and interval between chemotherapy and maintenance. The median follow-up was >19 mo in both arms. OS (primary endpoint), PFS, and safety were assessed. Hazard ratios (95% confidence interval) for OS with avelumab + BSC versus BSC alone were as follows: by chemotherapy duration-<Q1: 0.65 (0.42-1.02), Q1-Q2: 0.79 (0.50-1.27), Q2-Q3: 0.74 (0.50-1.10), and >Q3: 0.63 (0.39-1.00); by number of cycles-four cycles: 0.69 (0.48-1.00), five cycles: 0.98 (0.57-1.71), and six cycles: 0.66 (0.47-0.92); and by interval-4-<6 wk: 0.75 (0.54-1.04), 6-<8 wk: 0.67 (0.43-1.06), and 8-10 wk: 0.69 (0.47-1.02). Results were similar for PFS. Safety was similar across subgroups. All analyses were exploratory. Post hoc analyses of OS and PFS in subgroups defined by first-line chemotherapy duration and interval before maintenance were generally consistent with the results in the overall population, with similar safety findings. Prospective trials are warranted to confirm these findings. Avelumab maintenance treatment helped patients with advanced urothelial cancer without disease progression after at least four cycles of prior chemotherapy, and who started maintenance treatment at least 4 wk after chemotherapy, to live longer.

Sections du résumé

BACKGROUND BACKGROUND
In the JAVELIN Bladder 100 phase 3 trial, avelumab first-line maintenance + best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (advanced UC) without progression after first-line platinum-based chemotherapy.
OBJECTIVE OBJECTIVE
To report post hoc analyses of subgroups defined by the duration of first-line chemotherapy and interval before maintenance.
DESIGN, SETTING, AND PARTICIPANTS METHODS
Patients with advanced UC without progression after four to six cycles of platinum-based chemotherapy and a 4-10-wk interval after chemotherapy (n = 700) were randomized to receive avelumab + BSC or BSC alone. Subgroups were defined by duration (quartile [Q]) and estimated number of cycles of chemotherapy, and interval between chemotherapy and maintenance. The median follow-up was >19 mo in both arms.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS METHODS
OS (primary endpoint), PFS, and safety were assessed.
RESULTS AND LIMITATIONS CONCLUSIONS
Hazard ratios (95% confidence interval) for OS with avelumab + BSC versus BSC alone were as follows: by chemotherapy duration-<Q1: 0.65 (0.42-1.02), Q1-Q2: 0.79 (0.50-1.27), Q2-Q3: 0.74 (0.50-1.10), and >Q3: 0.63 (0.39-1.00); by number of cycles-four cycles: 0.69 (0.48-1.00), five cycles: 0.98 (0.57-1.71), and six cycles: 0.66 (0.47-0.92); and by interval-4-<6 wk: 0.75 (0.54-1.04), 6-<8 wk: 0.67 (0.43-1.06), and 8-10 wk: 0.69 (0.47-1.02). Results were similar for PFS. Safety was similar across subgroups. All analyses were exploratory.
CONCLUSIONS CONCLUSIONS
Post hoc analyses of OS and PFS in subgroups defined by first-line chemotherapy duration and interval before maintenance were generally consistent with the results in the overall population, with similar safety findings. Prospective trials are warranted to confirm these findings.
PATIENT SUMMARY RESULTS
Avelumab maintenance treatment helped patients with advanced urothelial cancer without disease progression after at least four cycles of prior chemotherapy, and who started maintenance treatment at least 4 wk after chemotherapy, to live longer.

Identifiants

pubmed: 37714742
pii: S0302-2838(23)03020-8
doi: 10.1016/j.eururo.2023.08.001
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Srikala S Sridhar (SS)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Electronic address: Srikala.Sridhar@uhn.ca.

Thomas Powles (T)

Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew's Hospital, London, UK.

Miguel Á Climent Durán (MÁ)

Department of Medical Oncology, Instituto Valenciano de Oncología, València, Spain.

Se Hoon Park (SH)

Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Francesco Massari (F)

Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Antoine Thiery-Vuillemin (A)

Department of Medical Oncology, University Hospital Jean Minjoz, Besançon Cedex, France.

Begoña P Valderrama (BP)

Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Sevilla, Spain.

Anders Ullén (A)

Department of Pelvic Cancer, Genitourinary Oncology Unit, Karolinska University Hospital, Solna, Sweden; Department of Oncology-Pathology, Karolinska Institute, Solna, Sweden.

Norihiko Tsuchiya (N)

Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Jeanny B Aragon-Ching (JB)

Inova Schar Cancer Institute, Fairfax, VA, USA.

Shilpa Gupta (S)

Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.

Daniel P Petrylak (DP)

Yale Cancer Center, New Haven, CT, USA.

Joaquim Bellmunt (J)

Department of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Jing Wang (J)

Pfizer, Cambridge, MA, USA.

Robert J Laliberte (RJ)

Pfizer, Cambridge, MA, USA.

Alessandra di Pietro (A)

Pfizer srl, Milano, Italy.

Nuno Costa (N)

Pfizer, Porto Salvo, Portugal.

Petros Grivas (P)

University of Washington, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Cora N Sternberg (CN)

Hematology/Oncology, Meyer Cancer Center, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.

Yohann Loriot (Y)

Gustave Roussy, Department of Cancer Medicine, INSERMU981, Université Paris-Saclay, Villejuif, France.

Classifications MeSH