Abstract P2-17-02: A phase II study of bevacizumab in combination with modified FOLFOX6 in heavily pretreated patients with HER2-negative metastatic breast cancer
Authors: Li Ting , Wang Biyun , Hu Xichun , Wang Zhonghua , Zhang Jian , Sun Si , Cao Jun , Lv Fangfang , Wang Leiping , Zhang Sheng , Ni Chen , Wu Zhenhua , Xie Jie 
Published: May 2015

Abstract
Backgroud
Bevacizumab combined with modified FOLFOX6 (mFOLFOX6) is a standard regimen for colorectal cancer with good tolerability. Our previously published study by Sun et al showed a moderate efficacy and excellent safety of mFOLFOX6 for metastatic breast cancer (MBC). This study was to determine the efficacy and safety of adding bevacizumab to mFOLFOX6 in heavily pretreated patients with human epidermal growth factor receptor 2 (HER2)-negative MBC.
Patients and Methods
In this open label, single-arm phase II study, bevacizumab, 5 mg/kg every two weeks or 7.5 mg/kg every three weeks, in combination with mFOLFOX6, which were oxaliplatin 85mg/m2, leucovorin 400mg/m2 and 5-Fu 400mg/m2 intravenously on day 1 following 5-Fu 2400 mg/m2 continuous intravenously 46 hours every 2 weeks, was administered to patients who failed at least 2 prior chemotherapy regimens in metastatic setting. The prior exposure to taxane, anthracycline, vinorelbine, capecitabine and gemcitabine was 97.9%, 93.8%, 64.6%, 64.6% and 81.3%, respectively. The primary objective was progression free survival (PFS), and secondary objectives included objective response rate (ORR), overall survival (OS) and safety.
Results
48 patients were enrolled with a median of 49.5 years old (range, 34 to 73 years old) and a median of 3 prior chemotherapy regimens (range, 2 to 6). A median of 4.0 cycles (range, 0.5 to 8.0 cycles) were delivered with 45 patients undergoing treatment discontinuation, including 7 (14.6%) due to completion of 6 cycles, 1 (2.1%) due to completion of 8 cycles, 18 (37.5%) due to disease progression, 5 (10.4%) due to adverse events, 4 (8.3%) due to withdrawal of informed consent, 2 (4.2%) due to physician’s decision, 2 (4.2%) due to economic reasons and 6 (12.5%) with unknown causes. The median PFS was 6.0 months (95% confidence interval [CI], 3.6 to 8.5 months), ORR was 48.8% and median OS was 10.2 months (95% CI, 8.5 to 11.9 months). Most adverse events were grade 1 or 2 and grade 3 or 4 toxicities occurring in more than one patient were neutropenia (75.0%), leukopenia (50.0%), thrombocytopenia (20.8%) and anemia (6.3%).
Conclusion
Adding bevacizumab to mFOLFOX6 has significant anti-tumor activity and excellent safety in heavily pretreated HER2-negative MBC patients, which warrants conduct of further confirmative trials.
Adverse events compared with our historical mFOLFOX6 trial Sun et alLi et alToxicityGrade 3-4, n (%)Grade 3-4, n (%)Anemia0 (0)3 (6.3)Neutropenia14 (22.6)36 (75.0)*Thrombocytopenia9 (14.5)10 (20.8)Nausea/vomiting1 (1.6)0 (0)Diarrhea1 (1.6)0 (0)Neuropathy3 (4.8)0 (0)*&lt;0.05
Chemotherapy as the third line or beyond treatment for metastatic breast cancerStudyRegimensMedian Line, rangeNumber of PatientsORR (%)median PFS (months)median OS (months)Li et alBevacizumab+mFOLFOX64, 3-74848.86.010.2Aogi et alEribulin42114.31.97.3Cortes et alEribulin5, 3-626914.12.610.4Rha et alGemcitabine3121757Smorenburg et alGemcitabine32301.9 (median TTP)7.8Udom et alVinorelbine3, 3-520352.75 (median TTP)NARivera et alPaclitaxel33520NANARivera et alPaclitaxel43318NANAAbrams et alPaclitaxel≥317223NANANA=Not Available, TTP=Time To Progression
Citation Format: Ting Li, Biyun Wang, Xichun Hu, Zhonghua Wang, Jian Zhang, Si Sun, Jun Cao, Fangfang Lv, Leiping Wang, Sheng Zhang, Chen Ni, Zhenhua Wu, Jie Xie. A phase II study of bevacizumab in combination with modified FOLFOX6 in heavily pretreated patients with HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-17-02.