Abstract P5-10-15: First Safety Data from a Randomised Phase III (CIBOMA 2004- 01/GEICAM 2003-11) Trial Assessing Adjuvant Capecitabine Maintenance Therapy after Standard Chemotherapy for Triple-Negative Early Breast Cancer

Abstract

Background: A large adjuvant trial programme is exploring the role of capecitabine (C) in early breast cancer (EBC). CIBOMA 2004-01/GEICAM 2003-11 is a multicenter, international randomised phase III trial that focuses on adjuvant C maintenance therapy after conventional induction chemotherapy in triple-negative EBC. Here we report interim safety data from the trial. Materials and methods: Patients (pts) with operable, node-positive (or node-negative with tumour diameter ≥1 cm), hormone receptor-negative, HER2-negative EBC (central laboratory confirmation) who have received standard anthracycline-and/or taxane-containing chemotherapy in the (neo)adjuvant setting are eligible. Pts are randomised to receive 8 cycles of C (1000 mg/m2 bid, d1-14 q21d) (Arm A) or observation (Arm B). The primary endpoint is disease-free survival (DFS). Assuming 30% risk reduction in DFS rate at 5 years (from 64.7% to 73.7%, HR of 0.701) with a power of 80% and a two-tailed log-rank test at 0.05, 834 evaluable patients will be needed. With an expected drop-out rate of 5%, 876 pts will be included. We anticipate completing recruitment by the end of 2010. Efficacy analysis will be triggered after 255 events. Results: To date, 724 pts have been recruited; here we report safety data from the first 278 pts (136 in Arm A and 142 in Arm B). Baseline characteristics are well balanced between the treatment arms. Baseline Characteristics In total, 920 cycles of C were administered (median 8.0, range 0-8). All 8 cycles were completed by 74.3% of pts. Median relative dose-intensity of C was 91.1%. The most common grade 3/4 clinical AEs related to C were: hand-foot syndrome (Grade 3 19.1%), diarrhoea (3.0%), vomiting (1.5%), fatigue (1.5%), nail changes (1.5%) and bilirubin elevation (1.5%). Conclusions: The safety profile of adjuvant C as maintenance therapy is consistent with its known toxicity profile. Safety data from the first 400 randomised pts will be reviewed by an Independent Data Monitoring Committee and used to update this analysis at the meeting. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-15.

Extended Adjuvant Chemotherapy in Triple-Negative Breast Cancer

“…The primary endpoint was DFS. The first safety data, presented at the 2010 San Antonio Cancer Symposium [22], revealed that the safety profile of adjuvant X as maintenance therapy was consistent with its known toxicity profile. More than 75% of patients were able to continue their treatment as planned with approximately 15% discontinuing due to toxicity or withdrawal.…”

Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy – A single-arm phase II study

“…The first safety data from the randomized phase III (CIBOMA 2004-01/GEICAM 2003-11) trial were published by Lluch et al in San Antonio cancer symposium 2010 revealing that more than 75% of patients were able to continue their treatment as planned with approximately 15% of patients discontinuing due to toxicity or withdrawal. Grade 3 or 4 adverse effects were higher in extended adjuvant capecitabine treatment, hand foot syndrome 17.4%, diarrhea 2.9%, vomiting 1.0%, and elevated bilirubin 1.0% [41]. This preliminary safety analyses on 405 patients reported 7 serious adverse events considered possibly related to capecitabine (hospitalization for grade 2-4 diarrhea in 3 patients; grade 2 thoracic pain, grade 2 arrhythmia, coronary vasospasm and chest pain in 1 patient each) [14].…”

“…There are several ongoing studies that include phase III trials which explore the addition of capecitabine to standard adjuvant chemotherapy, or through introduction of maintenance therapy [40][41][42].…”

The Role of Capecitabine in Early Stage Breast Cancer

“…Subgroup analysis of a few trials performed in advanced disease have suggested lack of activity [43,44], [47]. Accrual (876 patients) has been completed and final results are eagerly awaited, as this is one of the first adjuvant studies specifically targeting this subtype of EBC patients.…”