Abstract GS2-04: Efficacy results from CIBOMA/2004-01_GEICAM/2003-11 study: A randomized phase III trial assessing adjuvant capecitabine after standard chemotherapy for patients with early triple negative breast cancer

Background: Triple negative breast cancers (TNBC) have a greater risk of relapse than non-TNBC. New therapeutic approaches are needed for these patients (pts). CIBOMA/2004-01_GEICAM/2003-11 is a multinational, randomized phase III trial exploring adjuvant capecitabine (X) after completion of standard treatment in early TNBC pts. Materials and Methods: Patients with operable, node-positive (or node-negative with tumor size ≥ 1 cm), centrally confirmed hormone receptor-negative, HER2-negative early BC, who had received 6–8 cycles (cy) of standard anthracycline and/or taxane-containing chemotherapy or 4 cy of doxorubicin-cyclophosphamide (for node-negative disease) in the (neo)adjuvant setting, were eligible. Patients were randomized to either 8 cy of X (1,000 mg/m2 bid, days 1–14, every 3 weeks) or observation. Stratification factors included center, prior taxane-based therapy, number of involved axillary lymph nodes and phenotype (basal vs non-basal, according to cytokeratins 5/6 and/or EGFR positivity). The primary objective was to compare the disease-free survival (DFS) between both treatment arms, and secondary objectives included the comparison in terms of 5-year DFS, overall survival (OS) and safety. Assuming a 30% risk reduction in DFS rate at 5 years (from 64.7% to 73.7%, hazard ratio 0.70) with 80% power and a two-tailed log-rank test at 0.05, 834 evaluable pts were needed. 876 pts had to be finally enrolled considering a drop-out rate of 5%. Results: Recruitment of 876 pts from 8 countries was completed in September 2011. Median age was 49 years; 68.5% of pts were postmenopausal, 55.5% were lymph node negative, 71.7% had a basal phenotype, 67.5% received chemotherapy based on anthracyclines and taxanes. Median follow-up was 7.3 years (range 0.0 to 11.1). DFS was not significantly prolonged with X vs observation (hazard ratio (HR) 0.82; 95% confidence interval (CI), 0.63 to 1.06; P=0.1353). Five-year DFS was 79.6% (95% CI, 75.8% to 83.4%) with X and 76.8% (95% CI, 72.7% to 80.9%) with observation. OS was not statistically different between treatment arms (HR 0.92; 95% CI, 0.66 to 1.28; P=0.6228). In subgroup analysis for DFS, we found no statistically significant interaction between X treatment and different subgroups, with the exception of basal vs non-basal phenotypes (basal HR 0.97, 95% CI 0.72 to 1.32, P=0.8620; non-basal HR 0.51, 95% CI, 0.31 to 0.86, P=0.0101; interaction P=0.0357). Similar results were found for OS (basal HR 1.20, 95% CI 0.81 to 1.77, P=0.3684; non-basal HR 0.48, 95% CI, 0.26 to 0.91, P=0.0205; interaction P=0.0155). 75.2% of pts completed 8 cy of X, with a median relative dose intensity of 86.3%. Grade (G) 3 or higher adverse events (AEs) were observed in 40.4% of pts in X arm. In 9.6% of pts the AEs were related with X. Hand-foot syndrome was the most common AE in X arm (G3 on 18.8% of pts). Conclusions: In our study, the addition of adjuvant X after standard (neo) adjuvant anthracycline and/or taxane-containing chemotherapy was not associated with a statistically significant improvement of DFS or OS compared to observation in pts with early TNBC. However, in a subgroup analysis a significant DFS and OS improvement was observed with X in pts with non-basal phenotype. Sponsor: CIBOMA. Citation Format: Martin M, Barrios CH, Torrecillas L, Ruiz-Borrego M, Bines J, Segalla J, Ruiz A, Garcia-Saenz JA, Torres R, de la Haba J, Garcia E, Gomez HL, Llombart A, Rodriguez de la Borbolla M, Baena JM, Barnadas A, Calvo L, Perez-Michel L, Ramos M, Castellanos J, Rodriguez-Lescure A, Cardenas J, Vinholes J, Martinez de Duenas E, Godes MJ, Segui MA, Anton A, Lopez-Alvarez P, Moncayo J, Amorim G, Villar E, Reyes S, Sampaio C, Cardemil B, Escudero MJ, Bezares S, Carrasco E, Lluch A. Efficacy results from CIBOMA/2004-01_GEICAM/2003-11 study: A randomized phase III trial assessing adjuvant capecitabine after standard chemotherapy for patients with early triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-04.