Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01)
Authors: Lluch Ana , Barrios Carlos H. , Torrecillas Laura , Ruiz-Borrego Manuel , Bines Jose , Segalla Jose , Guerrero-Zotano Ángel , García-Sáenz Jose A. , Torres Roberto , de la Haba Juan , García-Martínez Elena , Gómez Henry L. , Llombart Antonio , Bofill Javier Salvador , Baena-Cañada José M. , Barnadas Agustí , Calvo Lourdes , Pérez-Michel Laura , Ramos Manuel , Fernández Isaura , Rodríguez-Lescure Álvaro , Cárdenas Jesús , Vinholes Jeferson , Martínez de Dueñas Eduardo , Godes Maria J. , Seguí Miguel A. , Antón Antonio , López-Álvarez Pilar , Moncayo Jorge , Amorim Gilberto , Villar Esther , Reyes Salvador , Sampaio Carlos , Cardemil Bernardita , Escudero Maria J. , Bezares Susana , Carrasco Eva , Martín Miguel ,   on behalf of GEICAM Spanish Breast Cancer Group,   CIBOMA (Iberoamerican Coalition for Research in Breast Oncology),   and LACOG (Latin American Cooperative Oncology Group)
Published: December 2019

PURPOSE Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. PATIENTS AND METHODS Eligible patients were those with operable, node-positive—or node negative with tumor 1 cm or greater—TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. RESULTS Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P = .136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P = .0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P = .0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. CONCLUSION This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation.