Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate - The ICE randomized clinical trial

Eur J Cancer. 2023 Nov:194:113324. doi: 10.1016/j.ejca.2023.113324. Epub 2023 Sep 7.

Abstract

Aim of the study: Evaluation of the impact of a de-escaleted chemotherapy regimen consisting of capecitabine (Cap) on invasive disease-free survival (iDFS) in patients ≥65 years with node-positive/high-risk node-negative early breast cancer (BC) receiving ibandronate (Ib).

Methods: ICE (Ib with or without Cap in Elderly patients with early breast cancer) was a multicentre phase 3 clinical trial with a 2020 update of long-term follow-up for overall survival enroling node-positive/high-risk node-negative patients ≥65 years with early BC. Patients were randomised to Cap 2000 mg/m² day 1-14 q3w for 6 cycles plus Ib (50 mg p.o. daily or alternatively 6 mg intravenous q4w) or Ib alone for 2 years. Endocrine therapy was recommended for hormone receptor (HR)-positive patients. The primary endpoint was iDFS analysed using Cox proportional hazards regression and log-rank analysis.

Results: 1358 (96.4%) of 1409 randomised patients started treatment. 564 (83.4%) completed 6 cycles of Cap. 513 (77.7%) and 516 (78.8%) completed Ib in the Cap+Ib and Ib alone arm, respectively. Median age was 71 (range 64-88) years, 1099 (81%) were HR-positive, 705 (51.9%) node-negative. At a median follow-up of 61.3 months, 5-year iDFS was 78.8% for Cap+Ib versus 75.0% for Ib alone (p = 0.80). Effects were independent of age, nodal, and HR status. The addition of Cap caused significantly higher skin and gastrointestinal toxicity.

Conclusions: The adjuvant combination of Cap+Ib did not show significantly better iDFS than Ib alone in node-positive/high-risk node-negative older BC patients, of whom HR-positive patients were also treated with endocrine therapy.

Trial registration: Study in elderly patients with early breast cancer (ICE), NCT00196859, https://clinicaltrials.gov/ct2/show/NCT00196859?term=NCT00196859.

Keywords: Adjuvant therapy; Breast cancer; Capecitabine; Clinical trial; Ibandronate.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms*
  • Capecitabine
  • Disease-Free Survival
  • Female
  • Humans
  • Ibandronic Acid / therapeutic use
  • Middle Aged

Substances

  • Capecitabine
  • Ibandronic Acid

Associated data

  • ClinicalTrials.gov/NCT00196859