Abstract P2-16-02: Bevacizumab, etoposide, and cisplatin (BEEP) is highly effective in brain metastases of HER2 positive breast cancer progressing from whole brain radiotherapy - Subgroup analysis of a multi-center phase II study
Authors: Lu Y-S , Chen W-W , Lin C-H , Yeh D-C , Tseng L-M , Rau K-M , Chen B-B , Chao T-C , Wu P-F , Huang S-M , Shih TT-F , Huang C-S , Cheng A-L 
Published: August 2014

Abstract
Background: We have recently reported that starting bevacizumab (BE) 1 day before chemotherapy could further induce tumor vascular normalization, thereby significantly enhanced the activity of etoposide (E) and cisplatin (P) in breast cancer patients (pts) with progressing brain metastases after whole brain radiotherapy (WBRT) (ESMO 2013). Lapatinib plus capecitabine is the only proven active regimen for the treatment of brain metastases of HER2 positive breast cancer, with a central nerve system (CNS) objective response rate (ORR) of 18-38% and median time to progression (TTP) of 3.6-5.1 months (mo) in those who had had prior WBRT.
Material and methods: Twenty-three HER2 positive breast cancer pts with progressing brain metastases after WBRT were enrolled from Jan 2011 to Jan 2013. Protocol treatment was given in 21 day cycles: BE 15 mg/kg on day 1, E 70 mg/m2/day from day 2 to day 4, and P 70 mg/m2 on day 2 (BEEP regimen), for a maximum of 6 cycles. The primary endpoint was a centrally assessed CNS ORR. A CNS objective response was defined as a ≥50% reduction in the volumetric sum of all measurable CNS lesions in the absence of increasing steroid use, development of new CNS lesion, or progressive neurologic symptoms. This trial is registered with ClinicalTrials.gov (NCT01281696).
Results: Median age was 55.1 (range 33-75); 9 pts were ER+, 14 pts were ER-; 15 pts were ECOG 0-2 (65.2%), and 8 pts were ECOG 3 (34.8%). All of them had previous exposure to trastuzumab, and 20 (87.0%) of them had received trastuzumab containing regimen for the treatment of metastatic disease. Eleven pts (47.8%) received lapatinib treatment before enrollment into this trial. The median lines of chemotherapy for the treatment of metastatic disease were 3 (range 1-8). The median BEEP treatment cycles were 6 (range 1-6). Sixteen of 23 pts (69.6%; 95%CI 47.1-86.8) achieved CNS objective response, including 6 pts (26.1%) with ≥80% and 10 pts (43.5%) with 50-80% CNS volumetric reduction, respectively. Five pts (21.7%) had 20-50% CNS volumetric reduction. Seven of 11 (63.6%) who were refractory to lapatinib treatment had CNS tumor response, and 9 of 12 (75.0%) who were lapatinib naive had CNS ORR. With median follow-up of 12.1 months (mo), the median time to progression was 7.7 mo (95% CI 6.6-8.8), and overall survival was 11.8 mo (95% CI 7.0-16.6) among the 23 pts. Only 3 pts (13.0%) had disease progression during protocol treatment. Grade 3/4 toxicities (≥1%) included neutropenia, leukopenia, thrombocytopenia, infection, anemia, and in 32.7%, 14.0%, 8.4%, 8.4%, and 5.6% per cycles, respectively. Ten pts (43.5%) needed dose reduction of E to 60 mg/m2 and P to 60 mg/m2, and 2 pts discontinued from treatment due to toxicity.
Conclusions: BEEP regimen has a significant anti-tumor effect for HER2 positive breast cancer with brain metastasis which progresses after WBRT.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-02.