Outcomes by Retrospective Eligibility for Maintenance Therapy of Patients With Advanced Urothelial Carcinoma: Post Hoc Analysis of the Phase 3 KEYNOTE-361 Trial

Clin Genitourin Cancer. 2025 Feb;23(1):102248. doi: 10.1016/j.clgc.2024.102248. Epub 2024 Oct 28.

Abstract

Introduction: The phase 3 KEYNOTE-361 trial of first-line pembrolizumab with or without chemotherapy versus chemotherapy alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) completed enrollment before the approval of postchemotherapy maintenance avelumab for patients without progressive disease. This post hoc analysis evaluated the outcomes of patients who received chemotherapy alone in KEYNOTE-361 by retrospective eligibility for subsequent maintenance therapy.

Patients and methods: Patients in the chemotherapy alone arm were retrospectively categorized as maintenance eligible (received ≥4 cycles of chemotherapy and did not die or experience disease progression within 10 weeks of chemotherapy completion), maintenance ineligible (received <4 cycles of chemotherapy or had progressive disease or died within 0-10 weeks after completion of ≥4 cycles of chemotherapy), and indeterminate eligibility for maintenance therapy (if neither maintenance eligible or ineligible). End points included progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review and overall survival from randomization (start of chemotherapy).

Results: Median follow-up was 31.7 months (range, 22.0-42.3). Among 342 patients who received chemotherapy alone, 172 (50.3%) were maintenance eligible, 108 (31.6%) were maintenance ineligible, and 62 (18.1%) had indeterminate eligibility for maintenance therapy. The median progression-free survival was 9.0 months (95% CI 8.4-10.4) in maintenance-eligible patients, 5.1 months (4.2-6.0) in maintenance-ineligible patients, and 2.3 months (1.9-3.8) in the indeterminate group; median overall survival was 23.3 months (95% CI 19.4-26.1), 10.2 months (9.1-11.6), and 5.5 months (3.7-8.5), respectively.

Conclusion: This post hoc analysis suggests that a majority of patients with untreated la/mUC who initiated chemotherapy in a clinical trial may have been considered eligible for maintenance therapy and had favorable survival outcomes compared with those considered maintenance ineligible.

Keywords: Advanced or metastatic urothelial carcinoma; Chemotherapy; Immunotherapy; Maintenance eligibility; Pembrolizumab.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Transitional Cell / drug therapy
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology
  • Female
  • Humans
  • Maintenance Chemotherapy* / methods
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Retrospective Studies
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / pathology
  • Urologic Neoplasms / drug therapy
  • Urologic Neoplasms / mortality
  • Urologic Neoplasms / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • pembrolizumab
  • avelumab