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.

Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer

“…From these databases, HER2-negative tumors with known IHC and HER2 amplification status were extracted 10 – 13 . Other patients were extracted from internal databases from the Hospital Clinic (Barcelona, Spain), from two SOLTI clinical trials (SOLTI 1501-VENTANA and SOLTI 1402-CORALEEN) 14 , 15 , from the Spanish Cancer Research Group (GEICAM)/CIBOMA study 16 and from a previously published collaboration between Hospital Clinic (Barcelona, Spain), Hospital Vall d’Hebron (Barcelona, Spain), University Campus Bio-Medico (Roma, Italy) and GEICAM 17 (see Supplementary Table 9 for study details). All studies had received proper ethical approval by the local institutional research ethics committee of all participating institutions and patients had given their consent to participate.…”

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

“…A total of 3842 TNBC patients were included in this meta-analysis. In two of the trials, the entire cohort of patients had TNBC [ 19 , 21 ], while in the other seven trials TNBC patients were one of the subgroups. The main research features are shown in Table 1 .…”

“…There were five [ 14 , 17 – 19 , 21 ] and four [ 15 , 16 , 20 , 22 ] studies involving the addition or replacement of capecitabine to neoadjuvant or adjuvant chemotherapy, respectively. From the available data of TNBC, there were 1373 capecitabine combined and 1356 capecitabine-free cases in the group with the addition of capecitabine, and 384 capecitabine combined and 357 capecitabine-free cases in the group with the replacement of capecitabine.…”

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

“…Indeed, in the preliminary results of a phase III GEICAM/CIBOMA trial, which enrolled 876 Caucasian women with early-stage TNBC treated with (neo)-adjuvant chemotherapy, the extension with adjuvant capecitabine versus placebo did not significantly improve 5-year DFS (80% vs. 77%) and OS (86.2% vs. 85.9%) in the whole study population, although in a pre-specified subgroup analysis, a significant survival benefit was reported among patients with no basal-like TNBC [66].…”