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

Alisha Sharma; Karlee Searle; Salwa Hasan; Stephanie Chan; Gregory Pond; Katarzyna J Jerzak

doi:10.1016/j.clbc.2022.07.004

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.

Authors

Alisha Sharma¹, Karlee Searle², Salwa Hasan³, Stephanie Chan⁴, Gregory Pond⁵, Katarzyna J Jerzak⁶

Affiliations

¹ Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
² McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada.
³ Faculty of Medicine, University of Toronto, Toronto, Canada.
⁴ Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
⁵ Department of Oncology, Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, Canada.
⁶ Division of Medical Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: katarzyna.jerzak@sunnybrook.ca.

PMID: 35965204
DOI: 10.1016/j.clbc.2022.07.004

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