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)

Abstract

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.

FIG 1.

All patients enrolled (N = 876) were included in the efficacy analyses. All patients who had received at least 1 cycle of study treatment (n = 861) were evaluated for safety. Safety population: In the capecitabine arm, all patients who have completed at least one cycle of study treatment and in the observation arm, all patients with a follow-up period ≥ 14 days. *Reasons of death on these patients: psychiatric disorder, cerebral hemorrhage, septic shock secondary to respiratory infection and stroke (not related with capecitabine). †Discontinuation of initial follow-up period (equivalent to treatment period in capecitabine arm). ‡Reasons of death on these patients: acute myocardial infarction and pulmonary sepsis.

FIG 2.

(A, C, D) Disease-free survival (DFS) and (B, E, F) overall survival (OS) Kaplan-Meier curves on the intention-to-treat population and subpopulations based on the immunohistochemistry phenotype.

FIG 3.

Subgroup analysis for disease-free survival (DFS) on the intention-to-treat (ITT) population. HR, hazard ratio.