UCBG 2-08: 5-year efficacy results from the UNICANCER-PACS08 randomised phase III trial of adjuvant treatment with FEC100 and then either docetaxel or ixabepilone in patients with early-stage, poor prognosis breast cancer

Eur J Cancer. 2018 Nov:103:184-194. doi: 10.1016/j.ejca.2018.06.025. Epub 2018 Sep 26.

Abstract

Purpose: UNICANCER-PACS08 compared adjuvant FEC (5-FU; epirubicin; cyclophosphamide) then docetaxel to FEC then ixabepilone in poor prognosis early breast cancer (BC). We evaluated whether replacing docetaxel with ixabepilone would increase 5-year disease-free survival (DFS).

Patients and methods: Triple-negative breast cancer (TNBC) or oestrogen receptor (ER)+/progesterone receptor (PR)-/HER2- BC patients were randomised to receive standard FEC (3 cycles) followed by 3 cycles of either docetaxel (100 mg/m2) or ixabepilone (40 mg/m2). Radiotherapy was mandatory after conservative surgery; ER+ patients received endocrine therapy.

Results: Seven hundred sixty-two patients were enrolled between October 2007 and September 2010. Baseline characteristics were balanced between arms. Median follow-up was 66.7 months. Median DFS was not reached; 5-year DFS rate was 76% with docetaxel and 79% with ixabepilone (hazard ratio [HR] = 0.80; 95% confidence interval [CI] = 0.58-1.10; p = 0.175). Median overall survival (OS) was not reached; 5-year OS rate was 86% versus 84% (HR = 0.97; 95% CI = 0.66-1.42; p = 0.897). TNBC patients treated with ixabepilone had a 23% lower risk of relapse compared to docetaxel (HR for DFS = 0.77; 95% CI = 0.53-1.11; p = 0.168). DFS was longer with ixabepilone than docetaxel in patients with grade II-III lymphocytic infiltration (HR = 0.55; 95% CI = 0.29-1.05; p = 0.063). All patients experienced ≥1 adverse events (AEs): 75% reported grade III-IV AEs and two (<1%) had grade V AEs (both with neutropenia and infection receiving ixabepilone).

Conclusion: After adjuvant FEC, ixabepilone was comparable to docetaxel for treating poor prognosis early BC patients. The benefit of ixabepilone in subgroups (patients with TNBC and grade II-III lymphocytic infiltration) requires further evaluation.

Keywords: Adjuvant chemotherapy; Docetaxel; Early breast cancer; Ixabepilone; Poor prognosis breast cancer; Triple-negative breast cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant / methods*
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use*
  • Docetaxel / pharmacology
  • Docetaxel / therapeutic use*
  • Epirubicin / pharmacology
  • Epirubicin / therapeutic use*
  • Epothilones / pharmacology
  • Epothilones / therapeutic use*
  • Female
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use*
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Survival Analysis
  • Young Adult

Substances

  • Epothilones
  • Docetaxel
  • Epirubicin
  • Cyclophosphamide
  • ixabepilone
  • Fluorouracil