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.

Background: Neratinib (HKI-272) is an irreversible pan-ErbB receptor tyrosine kinase inhibitor that has shown antitumor activity in patients with ErbB2+ breast cancer. Capecitabine has demonstrated efficacy and tolerability in combination with lapatinib, a reversible dual ErbB1/ErbB2 kinase inhibitor, in patients with ErbB2+ advanced breast cancer. The current study evaluated the safety and clinical activity of neratinib in combination with capecitabine. Methods: In part 1 of this open-label, phase 1/2 study, the maximum tolerated dose (MTD) of neratinib in combination with capecitabine was determined in adults with advanced solid tumors. Part 2 of the study further evaluated the safety and clinical activity of neratinib plus capecitabine at the MTD in adults with confirmed ErbB2+ metastatic or locally advanced breast cancer (ECOG Performance Status of 0–2). Eligible patients had received prior taxane treatment and ≥1 prior trastuzumab-containing regimen for ≥6 weeks for metastatic or locally advanced disease. The primary endpoint of part 2 was objective response rate (ORR); tumor responses were assessed by investigators using modified RECIST version 1.0 guidelines every 6 weeks. Results: In part 1 (n = 33), the MTD was determined to be neratinib 240 mg/day plus capecitabine 750 mg/m2 twice daily on Days 1 to 14 of each 21-day cycle. In part 2, as of April 2011, 72 female patients (median age of 52 years [range, 33–79 years]) with ErbB2+ breast cancer were enrolled and treated at the MTD; 7 patients had prior lapatinib exposure and all had prior trastuzumab and taxane exposure. As of the snapshot date, 56% of patients at the MTD were still participating in the study. The most common drug-related adverse events (AEs) in part 2 were diarrhea (89%), palmar-plantar erythrodysesthesia (57%), nausea (33%), vomiting (26%), and decreased appetite (22%). Grade 3/4 drug-related AEs in ≥5% of patients were diarrhea (25%) and palmar-plantar erythrodysesthesia (13%). Eight patients withdrew from part 2 due to AEs, including 4 who withdrew due to diarrhea. Dose interruptions of neratinib and capecitabine, respectively, due to AEs were required by 19 and 29 patients; dose reductions due to AEs were required by 8 and 22 patients. As of June 2010 (interim analysis), 22 patients were evaluable for efficacy in part 2 of the study. Of these 22 patients, 11 achieved a partial response for an ORR of 50%. An additional 2 patients maintained stable disease for ≥24 weeks, resulting in a clinical benefit rate of 59%, and 8 patients had stable disease for <24 weeks. One patient had progressive disease without achieving a response or stable disease. Updated efficacy data will be presented. Conclusions: The results of this study indicate that neratinib combined with capecitabine is tolerable and has promising antitumor activity in patients with ErbB2+ metastatic or locally advanced breast cancer pretreated with trastuzumab. This study supports further evaluation of this combination in ErbB2+ breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-09.