Abstract
Introduction: 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 (QoL) 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. Methods: Patients with stage I/II HER2-negative breast cancer received PLD (37.5 mg/m2, Q3W, 5 cycles, LC arm) plus cyclophosphamide (600 mg/m2) or epirubicin (90 mg/m2, Q3W, 4 cycles, EC arm) plus cyclophosphamide (600 mg/m2). Randomization was stratified by lymph node and ER and PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and QoL. QoL was assessed using the EORTC-QLQ-C30 and QLQ-BR23 questionnaires. Results: 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 the two groups. LC-based adjuvant regimens had significantly less alopecia and low-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. Conclusion: Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in the 5-year DFS and OS rates between the two treatment arms. However, low-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.
Plain Language Summary
This study compared two chemotherapy treatments for human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer: one using a drug called pegylated liposomal doxorubicin (PLD) and the other using epirubicin. A total of 256 women with stage I or II breast cancer from multiple medical centers in Taiwan were included in this study. They were randomly assigned to receive either PLD or epirubicin along with another drug called cyclophosphamide. Traditional treatments like anthracyclines (including doxorubicin and epirubicin) have been widely used but can have serious side effects. PLD is a newer drug that seems to work as well as traditional anthracyclines but with fewer harmful effects. The study found that both treatments were equally effective in 5-year disease-free survival and overall survival. However, the PLD treatment caused fewer severe side effects, such as hair loss and blood-related problems. Also, patients who received PLD reported feeling better during and after treatment compared to those who received epirubicin. This study is one of the first to directly compare PLD and epirubicin in a randomized trial for HER2-negative early-stage breast cancer patients. The results suggest that PLD could be a treatment option for these patients, offering similar effectiveness with fewer side effects to epirubicin treatments.
