Effect of Epirubicin Plus Paclitaxel vs Epirubicin and Cyclophosphamide Followed by Paclitaxel on Disease-Free Survival Among Patients With Operable ERBB2-Negative and Lymph Node-Positive Breast Cancer: A Randomized Clinical Trial

Abstract

Importance: Adjuvant therapy is an important and effective treatment for breast cancer. However, there is a lack of head-to-head clinical trials comparing the regimens epirubicin plus paclitaxel (EP) vs epirubicin and cyclophosphamide followed by paclitaxel (EC-P) in breast cancer.

Objective: To evaluate the noninferiority of a cyclophosphamide-free (EP) regimen compared with the standard EC-P regimen for patients with operable hormone receptor-positive, ERBB2 (formerly HER2)-negative, lymph node-positive breast cancer.

Design, setting, and participants: This prospective, open-label, phase 3, noninferiority randomized clinical trial was conducted from June 1, 2010, to June 30, 2016, in the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing. Patients with hormone receptor-positive, ERBB2-negative, lymph node-positive operable breast cancer were included and randomized into 2 treatment groups. Data were analyzed from June 30, 2016, to November 1, 2022.

Interventions: Patients received adjuvant epirubicin (75 mg/m2) and paclitaxel (175 mg/m2) every 3 weeks for 6 cycles (EP regimen) or epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for 4 cycles followed by paclitaxel (175 mg/m2) every 3 weeks for 4 cycles (EC-P regimen) as the intention-to-treat (ITT) population.

Main outcomes and measures: The primary outcome was disease-free survival (DFS), and the secondary outcomes included overall survival (OS), distant DFS, and safety.

Results: A total of 900 patients were registered, and 813 eligible patients (median age, 48 [IQR, 41-56] years) were randomly assigned to the EP group (n = 407) or the EC-P group (n = 406) after the surgical procedure. Through a median follow-up of 93.6 (IQR, 60.9-114.1) months, the hazard ratio (HR) of DFS for EP vs EC-P was 0.82 (95% CI, 0.62-1.10; 5-year DFS, 86.0% vs 80.6%; noninferior P = .001). The 5-year OS for the ITT population treated with the EP or the EC-P regimen was 94.7% vs 95.0%, respectively (HR, 0.95 [95% CI, 0.61-1.49]). Patients in the EP group had more frequent toxic effect events than those in the EC-P group.

Conclusions and relevance: In this prospective, open-label, phase 3, randomized clinical trial, the EP regimen was noninferior to the EC-P regimen. These findings supported that the EP regimen could be an effective adjuvant chemotherapy regimen for women with ERBB2-negative breast cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT01134523.

Figure 1.. Study Flow Diagram

EP indicates epirubicin plus paclitaxel; EC-P, epirubicin and cyclophosphamide followed by paclitaxel; ITT, intention to treat.

Figure 2.. Kaplan-Meier Curves of Disease-Free Survival

A, For all patients, those in the epirubicin plus paclitaxel (EP) group had 89 events; those in the epirubicin and cyclophosphamide followed by paclitaxel (EC-P) group, 100 events. B, For patients with luminal A tumors, patients in the EP group had 21 events; those in the EC-P group, 19 events. C, For patients with luminal B tumors, patients in the EP group had 51 events; those in the EC-P group, 71 events. HR indicates hazard ratio.

Figure 3.. Kaplan-Meier Curves of Overall Survival

A, For all patients, those in the epirubicin plus paclitaxel (EP) group had 39 events; those in the epirubicin and cyclophosphamide followed by paclitaxel (EC-P) group, 38 events. B, For patients with luminal A tumors, patients in the EP group had 8 events; those in the EC-P group, 8 events. C, For patients with luminal B tumors, patients in the EP group had 24 events; those in the EC-P group, 27 events. HR indicates hazard ratio.