Phase II study of bavituximab plus docetaxel in patients with locally advanced or metastatic breast cancer
3005 Background: Phosphatidylserine (PS) is an anionic phospholipid normally present on the inside surface of cell membranes. PS becomes exposed on the outside surface of tumor endolethial cells. Bavituximab (B) is a novel anti-PS monoclonal antibody and has demonstrated preclinical synergistic antitumor activity when used in combination with docetaxel. Methods: This Simon 2-stage trial is designed to determine the overall response rate (CR+PR) in patients with locally advanced or metastatic breast cancer to a combination of weekly bavituximab (3 mg/kg) plus docetaxel (35 mg/m2) on days 1, 8, 15 of a 28-day cycle for up to 6 cycles. Following completion of docetaxel, weekly bavituximab is continued until progression or toxicity. If ≥ 6 responses are observed in the 15 pt enrolled to Stage A, an additional 31 pts will be enrolled to Stage B. Secondary objectives include time to tumor progression, duration of response, overall survival, and safety. Results: Data are available for the 15 female pts enrolled in Stage A of the trial. Median age was 49 years;13 had stage IV and 2 had recurrent/progressive stage III breast cancer at study entry. All patients received prior chemotherapy, 13 had surgery, 7 had hormone therapy and 5 had prior radiotherapy. Patients received a median of 6 cycles of treatment. All patients reported at least one AE, to date. The most common AEs (regardless of severity or causality) were alopecia, epistaxis, fatigue, back pain, diarrhea, nasal dryness, infusion related reaction, arthralgia, pyrexia, stomatitis and nail bed bleeding. Grade 3 drug-related AEs were back pain, headache, DVT (discontinued study treatment at week 3) and chest pain (SAE) starting during a docetaxel infusion, which recurred after completion of bavituximab, reported in one patient each. Using RECIST, the overall response rate in these 15 pt is 67% (95% confidence interval, 38–88%) for the intent-to-treat group and 71% (95% CI, 42–92%) for the 14 evaluable patients. All responses were confirmed at least 4 weeks later. Conclusions: Bavituximab plus docetaxel achieved an encouraging response rate in advanced/metastatic breast cancer in Stage A of this study. Enrollment in Stage B of the trial is expected to be completed with preliminary results available by the annual meeting. [Table: see text]