Landscape of neoadjuvant therapy in HER2-positive breast cancer: a systematic review and network meta-analysis.

Abstract

BACKGROUND:

The recommended preoperative approach for HER2-positive breast cancer is unclear. We aimed to investigate the following: i) what is the optimal neoadjuvant regimen and ii) whether anthracyclines could be excluded.

METHODS:

A systematic literature search in Medline, Embase and Web of Science databases was performed. Studies had to satisfy the following criteria: i) randomised controlled trials (RCTs), ii) enroled patients treated preoperatively for HER2-positive BC (breast cancer), iii) at least one treatment group received an anti-HER2 agent, iv) available information of any efficacy end-point and v) published in English. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. Pathologic complete response (pCR), event-free survival (EFS) and overall survival (OS) were the efficacy end-points of interest, and selected safety end-points were also analysed.

RESULTS:

A total of 11,049 patients with HER2-positive BC (46 RCTs) were included in the network meta-analysis, and 32 different regimens were evaluated. Dual anti-HER2-therapy, with pertuzumab or tyrosine kinase inhibitors, combined with chemotherapy was significantly superior to trastuzumab and chemotherapy in terms of pCR, EFS and OS. However, a higher risk of cardiotoxicity was observed with dual anti-HER2-therapy. Anthracycline-based chemotherapy was not associated with better efficacy outcomes in comparison with non-anthracycline-based chemotherapy. In anthracycline-free regimens, the addition of carboplatin presented numerically better efficacy outcomes.

CONCLUSION:

Dual HER2 blockade with chemotherapy is the recommended choice as neoadjuvant therapy for HER2-positive breast cancer, preferably by omitting anthracyclines in favour of carboplatin.

• Authors: Guillermo Villacampa, Alexios Matikas, Mafalda Oliveira, Aleix Prat, Tomás Pascual, Andri Papakonstantinou
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 190 Pg. 112885 (09 2023) ISSN: 1879-0852 [Electronic] England
• PMID: 37142539 (Publication Type: Meta-Analysis, Systematic Review, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Carboplatin
• Receptor, ErbB-2
• Trastuzumab
• Antibiotics, Antineoplastic
• Anthracyclines

Topics

• Humans
• Female
• Neoadjuvant Therapy (adverse effects)
• Carboplatin (therapeutic use)
• Network Meta-Analysis
• Receptor, ErbB-2 (analysis)
• Breast Neoplasms (pathology)
• Trastuzumab
• Antibiotics, Antineoplastic
• Anthracyclines (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)