Exclusion of Patients With Brain Metastases in Published Phase III Clinical Trials for Advanced Breast Cancer

Clin Breast Cancer. 2022 Oct;22(7):629-633. doi: 10.1016/j.clbc.2022.07.004. Epub 2022 Jul 11.

Abstract

Metastatic HER2-positive (HER2+) and triple-negative breast cancer (TNBC) confer a 30% or higher risk of developing brain metastases (BrM), but BrM is typically an exclusion criteria for clinical trials, which limits the generalizability of trial results to these patients. We therefore analysed trends in the enrollment of patients with BrM, as well as the use of outcomes specific to the central nervous system (CNS), in phase III clinical trials evaluating systemic therapy for patients with advanced HER2+ and/or TNBC. Notably, 10 of the 34 trials (29%, 95% confidence interval = 15.1%-47.5%) evaluated CNS-specific outcomes and trials that completely excluded patients with BrM were significantly less likely to meet their primary endpoint (n = 6/17, 35%) than those that permitted conditional enrollment (n = 13/15, 87%) (P = .005), suggesting that enrollment of patients with BrM is not detrimental to trial success.

Keywords: Brain Metastases; Breast Cancer; Clinical trial design; Oncology; Randomized controlled trials.

Publication types

  • Editorial

MeSH terms

  • Brain Neoplasms* / secondary
  • Brain Neoplasms* / therapy
  • Breast Neoplasms* / pathology
  • Clinical Trials, Phase III as Topic
  • Female
  • Humans
  • Receptor, ErbB-2
  • Triple Negative Breast Neoplasms* / therapy

Substances

  • Receptor, ErbB-2