Abstract 143P
Background
Neoadjuvant therapy (NAT) is the recommended approach to early HER2+ breast cancer (BC). Anthracycline (ANTR)-polychemotherapy (CT) regimens have been the first choice but newer combinations with multiple anti-HER2 agents with or without ANTR have also shown efficacy. The questions of the optimal combination and whether ANTR could be omitted remain.
Methods
A systematic literature review in the Medline, Embase and Web of Science databases was performed.Randomised controlled trials (RCTs) evaluating NAT for HER2+ BC with at least one group with anti-HER2 targeted treatment, were selected. Primary endpoint was pathological complete response (pCR) and secondary endpoints were event-free survival (EFS), overall survival (OS) and toxicity incidence. A frequentist NMA was performed using random-effect models for the estimation of odds-ratio (OR) and hazard ratio (HR) along with the 95% confidence interval (95% CI).
Results
The literature search identified 3384 records; 67 articles corresponding to 48 RCTs met the eligibility criteria and additional 4 articles (3 RCTs) published during data analysis were included. A total of 16,245 patients with early HER2+ BC were included in the global network. For the pCR endpoint (n=10,906), three combinations performed significantly better than trastuzumab (TRA) + CT: i) pertuzumab (PER) + TRA + CT, ii) single T-DM1 and iii) Tyrosine Kinase Inhibitors (TKI) + TRA + CT. In the EFS analysis (n=6,657), PER + TRA + CT and TKI + TRA + CT demonstrated superiority against single T-DM1 (HR: 0.45; 0.26-0.78 and HR: 0.41; 0.19-0.87, respectively). In a more aggregated analysis, the combination of dual anti-HER2 + CT associated with significantly better EFS and OS than i) dual anti-HER2 alone, ii) anti-HER2 + CT and iii) single T-DM1. Comparison of regimens with or without ANTR demonstrated no significant differences in pCR rates, but all estimations were in favour of the non-ANTR group. There was no difference in EFS either (HR: 1.00, 0.62 - 1.62). Similar safety profiles were observed with or without ANTR, with the exception of higher risk of LVEF drop with ANTR and dual anti-HER2 (PRE + TRA).
Conclusions
The combination of dual anti-HER2 + CT provides the best efficacy results. Additionally, this study provides evidence that anthracyclines can be safely omitted in early HER2+ BC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. Villacampa Javierre: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly. A. Matikas: Non-Financial Interests, Advisory Role: Veracyte. All other authors have declared no conflicts of interest.