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

• Published in: European journal of cancer (1990) 2023-11, Vol.194, p.113324-113324, Article 113324
• Main Authors: Schmidt, Marcus, Nitz, Ulrike, Reimer, Toralf, Schmatloch, Sabine, Graf, Heiko, Just, Marianne, Stickeler, Elmar, Untch, Michael, Runnebaum, Ingo, Belau, Antje, Huober, Jens, Jackisch, Christian, Hofmann, Manfred, Krocker, Jutta, Nekljudova, Valentina, Loibl, Sibylle
• Format: Article
• Language: English
• Subjects: Adjuvant therapy; Breast cancer; Capecitabine; Clinical trial; Ibandronate
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2023.113324

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). 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. 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. 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. Study in elderly patients with early breast cancer (ICE), NCT 00196859, https://clinicaltrials.gov/ct2/show/NCT00196859?term=NCT00196859. •ICE is the largest phase 3 trial on adjuvant therapy in older breast cancer patients.•1409 patients were randomised to ibandronate plus capecitabine vs. ibandronate alone.•Endocrine treatment was recommended for hormone receptor-positive patients.•5-year invasive disease-free survival was not significantly different in patients.•A numerical improvement of adjuvant capecitabine was observed overall survival.