Trastuzumab in combination with bevacizumab in advanced breast cancer patient resistant to chemotherapy

Abstract

10762 Background: HER2 positive is associated with up-regulation of VEGF in human breast cancer cells. Superior efficacy was observed if anti-HER2 antibody (trastuzumab) (TZB) is given with anti-VEGF antibody (bevacizumab) (BVB) in xenografs models (Konecny G., 2004). In one phase I study with 9 patients (pt), the combination TZB+BVB was well tolerated without important toxicity, achieving 1 complete response and 4 partial responses (Pegram M, 2005). Methods and Result: We report a clinical case of a 48 years old woman with an advanced resistant breast cancer diagnosed in 1995 and treated with radical surgery for a invasive ductal carcinoma pT2N1M0 HHRR - and c-erbB2 positive (+++). She received adjuvant CMF for 6 cycles and local radiotherapy (XRT). In 2000, lung and liver metastases (mts) with increased CA 15.3 serum levels and was treated with paclitaxel + TZB achieving complete response. Maintenance with TZB was given for one additional year. In 2002, bone and brain mts with increase of CA 15.3 and was treated with vinorelbine + TZB with whole brain irradiation. On March 2005, bone and liver progression was treated with capecitabine + TZB and pelvic XRT with control of the mts. On August, pt developed rapid progression of liver mts with intensive abdominal pain requiring high doses of morphine; progressive jaundice (total bilirubin: 24.4 mg/dl) and low performance status. The level of CA 15.3 was 626 U/ml. We decide treatment with TZB + BVB in a biweekly schedule for 6 consecutive weeks. Whole liver XRT was given in two weeks (15.5Gy). The treatment was well tolerated and the pt improves immediately her clinical situation. Levels of CA 15.3 dropped to 161 U/ml and bilirubin to 4.87 mg/dl. The pt continues the treatment in ambulatory regiment for 7 additional weeks. She had a pathological hip fracture at home and was admitted to the Hospital developing an acute lung tromboembolism dying suddenly. Liver metastases still in clinical and biochemical response. Conclusions: The combination of TZB with BVB could be an effective alternative treatment for pt with advanced and resistant breast cancer, erbB2 positive, and need to be explored in clinical trials. No significant financial relationships to disclose.