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

Abstract

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: Martín M, Barrios CH, Torrecillas L, Ruiz-Borrego M, Bines J, Segalla J, Ruiz A, García-Sáenz JA, Torres R, de la Haba J, García E, Gómez HL, Llombart A, Rodríguez de la Borbolla M, Baena JM, Barnadas A, Calvo L, Pérez-Michel L, Ramos M, Castellanos J, Rodríguez-Lescure A, Cárdenas J, Vinholes J, Martínez de Dueñas E, Godes MJ, Seguí MA, Antón A, López-Álvarez 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.

Triple-negative breast cancer: recent treatment advances

“…This randomised phase 3 trial of 876 patients who had early-stage TNBC and who had completed standard adjuvant or neoadjuvant polychemotherapy was designed to analyse the impact of adjuvant capecitabine (1000 mg/m 2 from days 1 to 14, every 21 days) for all patients with TNBC regardless of their pCR status. There was no significant difference in 5-year DFS and OS between the treatment groups, highlighting the need to choose a treatment-resistant group 47 . The results of the CREATE-X trial now compel most clinicians to treat early-stage TNBC with neoadjuvant chemotherapy in order to understand who should have capecitabine.…”

Update Mammakarzinom 2019 Teil 1 – Implementierung der Ergebnisse neuer Studienkonzepte beim frühen Mammakarzinom in die klinische Praxis

“…A difference could be detected only in a subgroup with non-basal TNBC carcinomas (EGFR and CK5/6 negative) (p = 0.020, HR: 0.53 [95 % CI: 0.31, 0.91]). However, since the study was negative overall, it was also concluded in the subsequent discussion that, outside of the conditions in the Create-X study, the use of capecitabine is not indicated in patients with TNBC [69].…”

“…The CIBOMA/2004-01_GEICAM/2003-11 study was conducted in a different study setting but with the same question regarding modified therapy [69]. This study, which was conducted in Spain and Latin America, admitted triple-negative patients following adjuvant or neoadjuvant chemotherapy who received further treatment after completing therapy with capecitabine or who did not receive any further therapy.…”

A Pilot Study of Extended Adjuvant Therapy with Metronomic Docetaxel for Patients with Operable Triple-Negative Breast Cancer

“…The largest phase III trials that investigated the extended adjuvant mCTH in TNBC are CIBOMA 2004-01/GEICAM 2003-11 and SYSCBS-001 trials. In CIBOMA trial, the efficacy and safety of maintenance therapy of capecitabine were evaluated after primary treatment in patients with early stages TNBC (Martín et al, 2018), while in SYSCBS-001, capecitabine was evaluated as in CIBOMA studies but with different dose and duration Zhong-yu., NCT01112826). Also, the efficacy of extended therapy with capecitabine was evaluated in a famous phase III trial, the CREATE-X trial that showed a significant improvement in survival in patients with TNBC with a residual disease after neoadjuvant therapy (Masuda et al, 2017).…”