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

Oncol Res Treat. 2024;47(10):484-495. doi: 10.1159/000540369. Epub 2024 Jul 19.

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.

Keywords: Disease-free survival; Epirubicin; HER2-negative breast cancer; Overall survival; Pegylated liposomal doxorubicin; Quality of life.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Chemotherapy, Adjuvant
  • Cyclophosphamide* / administration & dosage
  • Cyclophosphamide* / adverse effects
  • Cyclophosphamide* / therapeutic use
  • Doxorubicin* / adverse effects
  • Doxorubicin* / analogs & derivatives
  • Doxorubicin* / therapeutic use
  • Epirubicin* / administration & dosage
  • Epirubicin* / adverse effects
  • Epirubicin* / therapeutic use
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Polyethylene Glycols* / administration & dosage
  • Polyethylene Glycols* / therapeutic use
  • Prospective Studies
  • Quality of Life*
  • Receptor, ErbB-2* / metabolism
  • Treatment Outcome

Substances

  • Polyethylene Glycols
  • Epirubicin
  • Doxorubicin
  • liposomal doxorubicin
  • Cyclophosphamide
  • Receptor, ErbB-2
  • ERBB2 protein, human