Comparison of the efficacy, safety and quality of life of pegylated liposomal doxorubicin-cyclophosphamide versus epirubicin-cyclophosphamide in patients with early stage HER2-negative breast cancer: A prospective, randomized, multicenter, Phase II study.

Abstract

This multicenter, phase II randomized, non-inferiority study reports from the first prospective two-armed randomized control trial that compared the efficacy, safety and quality-of-life of pegylated liposomal doxorubicin (PLD)-based and epirubicin-based as adjuvant chemotherapy for stage I-II Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer. Patients with stage I/II HER2-negative breast cancer received PLD (37.5mg/m2, Q3W, 5 cycles, LC arm) plus cyclophosphamide (600mg/m2) or epirubicin (90mg/m2, Q3W, 4 cycles, EC arm) plus cyclophosphamide (600mg/m2). Randomization was stratified by lymph node, ER and PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and quality of life (QoL). QoL was assessed using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. A total of 256 patients were assigned to LC (n=148) and EC (n=108). There was no difference in 5-year DFS and OS rate between two groups. LC-based adjuvant regimens had significantly less alopecia, less grade 3-4 hematologic adverse events (AEs). Significantly improved QoL was observed in the LC arm during and after treatment for symptoms including fatigue, nausea and vomiting, and systemic therapy side effects. Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in 5-year DFS and OS rate between the two treatment arms. However, less grade 3-4 AEs and a trend of favorable QoL symptom scales were observed in the LC arm, suggesting that PLD-containing regimen could become a new standard treatment for early stage HER2-negative breast cancer patients.