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)

Lluch A.; Barrios C.H.; Torrecillas L.; Ruiz-Borrego M.; Bines J.; Segalla J.; Guerrero-Zotano A.; García-Saénz J.A.; Torres R.; de la Haba J.; García-Martínez E.; Gómez H.L.; Llombart A.; Bofill J.S.; Baena-Cañada J.M.; Barnadas A.; Calvo L.; Pérez-Michel L.; Ramos M.; Fernańdez I.; Rodríguez-Lescure A.; Cárdenas J.; Vinholes J.; de Dueñas E.M.; Godes M.J.; Seguí M.A.; Antoń A.; Loṕez-Álvarez P.; Moncayo J.; Amorim G.; Villar E.; Reyes S.; Sampaio C.; Cardemil B.; Escudero M.J.; Bezares S.; Carrasco E.; Martín M. · Journal of Clinical Oncology (2020) · DOI: 10.1200/jco.19.00904

Resumen

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. Copyright