Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial

BMJ Open. 2020 Oct 15;10(10):e035530. doi: 10.1136/bmjopen-2019-035530.

Abstract

Introduction: Atezolizumab is a programmed death ligand-1 inhibitor for urothelial bladder cancer treatment. Atezolizumab has become the standard therapy for patients with urothelial bladder cancer who are not responding to cisplatin-based chemotherapy and is also used as a first-line treatment in cisplatin-ineligible patients. However, the efficacy of atezolizumab as a neoadjuvant chemotherapy for radical cystectomy has not yet been published and is still under study. This trial investigates the effectiveness of basal/squamous-like (BASQ) classification in the selection of an effective target group of patients with muscle-invasive bladder cancer (MIBC) for neoadjuvant atezolizumab treatment.

Methods and analysis: This study is an open-label, two-cohort, phase II trial. It was designed to evaluate the efficacy of neoadjuvant atezolizumab treatment in patients with MIBC (T2-4N0M0) pathological responses after neoadjuvant chemotherapy and radical cystectomy. According to the molecular subtype characteristics of previous transurethral resection of the bladder specimens, patients are divided into two groups: luminal type (KRT5/6-KRT14-FOXA1+GATA3+) and basal type (KRT5/6+KRT14+FOXA1-GATA3-). Every 3 weeks, atezolizumab is administered at a dose of 1200 mg for three cycles prior to radical cystectomy in patients with MIBC. The primary end point is objective pathological responses in the intention-to-treat patients. The secondary end point is a 1-year progression-free survival difference according to the BASQ classification in patients who underwent neoadjuvant atezolizumab treatment.

Ethics and dissemination: The study protocol was approved by the Institutional Review Board of Seoul National University Hospital, Seoul, Republic of Korea (H 1806-051-950). The trial is registered at ClinicalTrials.gov. The trial results will be published in peer-reviewed journals and at conferences.

Trial registration number: NCT03577132.

Keywords: genitourinary medicine; immunology; urological tumours.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols
  • Clinical Trials, Phase II as Topic
  • Cystectomy
  • Humans
  • Neoadjuvant Therapy*
  • Republic of Korea
  • Seoul
  • Treatment Outcome
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / surgery

Substances

  • Antibodies, Monoclonal, Humanized
  • atezolizumab

Associated data

  • ClinicalTrials.gov/NCT03577132