Avelumab first-line maintenance therapy for advanced urothelial carcinoma: comprehensive clinical subgroup analyses from the JAVELIN Bladder 100 Phase 3 trial

Petros Grivas*, Se Hoon Park, Eric Voog, Claudia Caserta, Howard Gurney, Joaquim Bellmunt, Haralabos Kalofonos, Anders Ullén, Yohann Loriot, Srikala S. Sridhar, Yoshiaki Yamamoto, Daniel P. Petrylak, Cora N. Sternberg, Shilpa Gupta, Bo Huang, Nuno Costa, Robert J. Laliberte, Alessandra di Pietro, Begoña P. Valderrama, Thomas Powles

*Corresponding author for this work

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Abstract

Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab first-line (1L) maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (aUC) who were progression-free following 1L platinum-based chemotherapy, leading to regulatory approval in various countries. Objective: To analyze clinically relevant subgroups from JAVELIN Bladder 100. Design, setting, and participants: Patients with unresectable locally advanced or metastatic UC without progression on 1L gemcitabine + cisplatin or carboplatin were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350). Median follow-up was >19 mo in both arms (data cutoff October 21, 2019). This trial is registered on ClinicalTrials.gov as NCT02603432. Outcome measurements and statistical analysis: OS (primary endpoint) and PFS were analyzed in protocol-specified and post hoc subgroups using the Kaplan-Meier method and Cox proportional hazards models. Results and limitations: Hazard ratios (HRs) for OS with avelumab + BSC versus BSC alone were <1.0 across all subgroups examined, including patients treated with 1L cisplatin + gemcitabine (HR 0.69, 95% confidence interval [CI] 0.50–0.93) or carboplatin + gemcitabine (HR 0.64, 95% CI 0.46–0.90), patients with PD-L1+ tumors treated with carboplatin + gemcitabine (HR 0.67, 95% CI 0.39–1.14), and patients whose best response to chemotherapy was a complete response (HR 0.80, 95% CI 0.46–1.37), partial response (HR 0.62, 95% CI 0.46–0.84), or stable disease (HR 0.70, 95% CI 0.46–1.06). Observations were similar for PFS. Limitations include the smaller size and post hoc evaluation without multiplicity adjustment for some subgroups. Conclusions: Analyses of OS and PFS in clinically relevant subgroups were consistent with results for the overall population, further supporting avelumab 1L maintenance as standard-of-care treatment for patients with aUC who are progression-free following 1L platinum-based chemotherapy. Patient summary: In the JAVELIN Bladder 100 study, maintenance treatment with avelumab helped many different groups of people with advanced cancer of the urinary tract to live longer.

Original languageEnglish
Pages (from-to)95-108
Number of pages14
JournalEuropean Urology
Volume84
Issue number1
DOIs
Publication statusPublished - Jul 2023

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Bladder cancer
  • Clinical trial
  • Immunotherapy
  • Maintenance
  • Phase 3
  • Randomized
  • Urothelial carcinoma

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