HER2-targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: a systematic review and meta-analysis.

HER2/neu brain metastases breast cancer molecular targeted therapy

Journal

Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003

Informations de publication

Date de publication:
Historique:
entrez: 11 12 2020
pubmed: 12 12 2020
medline: 12 12 2020
Statut: epublish

Résumé

Intracranial metastatic disease (IMD) is a serious and known complication of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The role of targeted therapy for patients with HER2-positive breast cancer and IMD remains unclear. In this study, we sought to evaluate the effect of HER2-targeted therapy on IMD from HER2-positive breast cancer. We searched MEDLINE, EMBASE, CENTRAL, and gray literature sources for interventional and observational studies reporting survival, response, and safety outcomes for patients with IMD receiving HER2-targeted therapy. We pooled outcomes through meta-analysis and examined confounder effects through forest plot stratification and meta-regression. Evidence quality was evaluated using GRADE (PROSPERO CRD42020161209). A total of 97 studies (37 interventional and 60 observational) were included. HER2-targeted therapy was associated with prolonged overall survival (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.39-0.56) without significantly prolonged progression-free survival (HR 0.52; 95% CI, 0.27-1.02) versus non-targeted therapy; the intracranial objective response rate was 19% (95% CI, 12-27%), intracranial disease control rate 62% (95% CI, 55-69%), intracranial complete response rate 0% (95% CI, 0-0.01%), and grade 3+ adverse event rate 26% (95% CI, 11-45%). Risk of bias was high in 40% (39/97) of studies. These findings support a potential role for systemic HER2-targeted therapy in the treatment of patients with IMD from HER2-positive metastatic breast cancer.

Sections du résumé

BACKGROUND BACKGROUND
Intracranial metastatic disease (IMD) is a serious and known complication of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The role of targeted therapy for patients with HER2-positive breast cancer and IMD remains unclear. In this study, we sought to evaluate the effect of HER2-targeted therapy on IMD from HER2-positive breast cancer.
METHODS METHODS
We searched MEDLINE, EMBASE, CENTRAL, and gray literature sources for interventional and observational studies reporting survival, response, and safety outcomes for patients with IMD receiving HER2-targeted therapy. We pooled outcomes through meta-analysis and examined confounder effects through forest plot stratification and meta-regression. Evidence quality was evaluated using GRADE (PROSPERO CRD42020161209).
RESULTS RESULTS
A total of 97 studies (37 interventional and 60 observational) were included. HER2-targeted therapy was associated with prolonged overall survival (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.39-0.56) without significantly prolonged progression-free survival (HR 0.52; 95% CI, 0.27-1.02) versus non-targeted therapy; the intracranial objective response rate was 19% (95% CI, 12-27%), intracranial disease control rate 62% (95% CI, 55-69%), intracranial complete response rate 0% (95% CI, 0-0.01%), and grade 3+ adverse event rate 26% (95% CI, 11-45%). Risk of bias was high in 40% (39/97) of studies.
CONCLUSION CONCLUSIONS
These findings support a potential role for systemic HER2-targeted therapy in the treatment of patients with IMD from HER2-positive metastatic breast cancer.

Identifiants

pubmed: 33305268
doi: 10.1093/noajnl/vdaa136
pii: vdaa136
pmc: PMC7720818
doi:

Types de publication

Journal Article

Langues

eng

Pagination

vdaa136

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

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Auteurs

Anders W Erickson (AW)

Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Farinaz Ghodrati (F)

Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Steven Habbous (S)

Ontario Health (Cancer Care Ontario), Toronto, Ontario, Canada.

Katarzyna J Jerzak (KJ)

Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Arjun Sahgal (A)

Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Ontario, Canada.

Manmeet S Ahluwalia (MS)

Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, USA.

Sunit Das (S)

Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Division of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Classifications MeSH