Abstract P5-14-10: Weekly doxorubicin and daily oral cyclophosphamide followed by nab-paclitaxel for adjuvant therapy of high-risk localized breast cancer

Abstract

BACKGROUND: The addition of taxanes to anthracycline-based adjuvant chemotherapy has improved disease free survival (DFS) in women with high-risk early-stage breast cancer. Many studies have sought to optimize the dose intensity and density of these agents to produce improvements in outcome and tolerability. The purpose of this study was to assess the use of metronomic doxorubicin plus daily oral cyclophosphamide (AC) for 12 weeks followed by nab-paclitaxel (nP) for 12 weeks in this population. Those patients with Her2 positive disease were also given adjuvant trastuzumab. METHODS: A non-randomized phase II clinical trial was designed to (1) test the DFS at 2 years compared to historical controls, (2) assess dose intensity delivered, (3) assess use of nP in the adjuvant setting, and (4) evaluate toxicities associated with the regimen. Overall survival (OS) was a secondary outcome. The dosing of A was 24mg/m2 IV qweek and C was 60mg/m2 oral daily; nP, 100mg/m2 IV qweek. RESULTS: Sixty patients were enrolled on the study with a median follow-up of 6 years and a median age of 50 (range 30-69). 58% of patients had node positive disease. Receptor categories included hormone receptor positive (ER positive or PR positive) and HER2 negative (n=24; 40%); ER negative, PR negative, and HER2 negative (triple negative; n=19; 32%); or HER2 positive (n=17; 28%). DFS at 2 years was 93% (1 death, 3 recurrence) and at 6 years was 82%, comparable to historical controls. OS at 2 years and 6 years was 98% and 88%, respectively. Mean dose intensity was greater than 90% for AC and 88% for nP. Treatment was well-tolerated with the most common grade ≥3 toxicity being neutropenia and a 2% incidence of febrile neutropenia. Disease-free survival and overall survival at 2 and 6 years 2 year 6 year DFS %OS %DFS %OS %All patients93988288ER+ or PR+, HER2-921007979Triple negative89957989HER2+10010088100 CONCLUSSIONS: Patients achieved similar DFS to that seen in historical controls with similar rates of adverse events. Since nP dosing was 100 mg/m2, even with 88% dose intensity, the delivered taxane dose is greater than standard weekly paclitaxel. Notably disease control was particularly impressive in the triple negative subtype, which has been shown to benefit from nP over standard paclitaxel in the neoadjuvant setting in the GeparSepto (GBG 69) trial. Metronomic AC followed by nP is a safe, effective option for delivery of adjuvant chemotherapy for high-risk patients. Citation Format: Cho E, Wu Q, Rubinstein L, Linden H, Gralow J, Specht J, Gadi V, Ellis G. Weekly doxorubicin and daily oral cyclophosphamide followed by nab-paclitaxel for adjuvant therapy of high-risk localized breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-14-10.