142P - Effectiveness and safety of pegylated liposomal doxorubicin- cyclophosphamide vs. epirubicin-cyclophosphamide as adjuvant chemotherapy for stage I and II HER2-negative breast cancer: An interim analysis of phase II randomized trial

Background

Doxorubicin is a cornerstone drug for breast cancer treatment. Epirubicin is an effective epimer of doxorubicin with less cardiotoxicity, and pegylated liposomal doxorubicin (PLD), is a liposomal formulation with lower toxicity than doxorubicin. We report the interim efficacy and safety results from the first phase II randomized trial aimed to compare PLD-based and epirubicin-based adjuvant chemotherapy for stage I-II Her2-negative breast cancer.

Methods

Eligible patients with Her2-negative stage I or II invasive breast adenocarcinoma were randomized 1:1 to receive adjuvant cyclophosphamide 600mg/m² followed by pegylated liposomal-doxorubicin (Lipo-Dox®) 37.5mg/m² Q3W, 5 cycles (LC arm) or epirubicin 90mg/m² Q3W, 4 cycles (EC arm). Randomization was stratified by lymph node, ER & PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and quality of life (using EORTC QLQ-C30 & QLQ-BR23). The data cutoff date for the interim analysis was December 31, 2020.

Results

A total of 256 patients were randomized to LC (n=148) and EC (n=108). There was no difference in 2-year DFS rate between 2 arms (LC: 0.96; EC: 0.97, p=0.59), regardless of whether taxane was used. There was no difference in 2-year OS, mean change in LVEF, and BNP from screening to treatment after 3 weeks between the 2 arms. Compared to EC, there was less grade 3-4 AE in LC for: neutropenia (13.1% vs 34.3%), leukopenia (2.8% vs 24.8%), and vomiting (0 vs 3.8%) (All p<0.05). The major event in the LC arm are mucosal and dermal toxicities, whereas in the EC arm, the main toxicities are hematological and alopecia. The LC arm had a significantly better QoL score during and/or after treatment in symptoms including fatigue, nausea and vomiting, and systemic therapy side effects.

Conclusions

This interim analysis showed comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II Her2-negative breast cancer. In addition, less grade 3-4 AE and a trend of favorable QoL symptom scales were observed in the LC arm. Final analysis will be performed using longer survival data.

Clinical trial identification

NCT01210768. First posted: September 28, 2010.

Editorial acknowledgement

Legal entity responsible for the study

TTY Biopharm Company Ltd.

Funding

TTY Biopharm Company Ltd.

Disclosure

All authors have declared no conflicts of interest.