Abstract P6-12-08: Phase II Multicenter Study of Docetaxel and Bevacizumab (Bev) +/− Trastuzumab as First-Line Treatment of Patients with Metastatic Breast Cancer (MBC)

Background: The addition of Bev to the taxanes docetaxel and paclitaxel has resulted in improved progression-free survival (PFS) in the first line setting of HER2- MBC. The majority of data with docetaxel is from the AVADO study, which used a dose of 100 mg/m 2 of docetaxel. No data exists that combines Bev with docetaxel at the current U.S. standard dose of 75 mg/m 2 in HER2- MBC, or at any dose in the HER2+ setting. We report here the results of the feasibility, safety, and efficacy data of the combination of 75 mg/m 2 of docetaxel and bevacizumab in HER2- MBC, and the first reported results of docetaxel, Bev, and trastuzumab in HER2+ MBC. Methods: Phase II, nonrandomized, parallel arm study, stratified by HER2 status, conducted in a large community practice network. Eligibility: Histologically-proven breast adenocarcinoma, stage IV disease with at least one measurable lesion per RECIST criteria, ECOG PS 0-1, no prior chemotherapy for metastatic disease, no evidence or history of brain or leptomeningeal metastases. Stratum 1 (HER2-) treatment: Bev (15mg/kg) followed by docetaxel (75 mg/m 2 ) q 3 weeks. Stratum 2 (HER2+) treatment included in addition trastuzumab (8 mg/kg loading dose on day 2 of cycle 1, and 6 mg/kg on day 1 of all subsequent cycles). All subjects received G-CSF as primary prophylaxis. Treatment continued until unacceptable toxicity, disease progression, or death. Docetaxel could be discontinued after 8 cycles if a complete response (CR) was obtained with continuation of Bev (and trastuzumab in her-2+ pts) until disease progression. Primary endpoint: Progress-free survival (PFS) in each stratum. Secondary endpoints: overall response rate (ORR), clinical benefit rate (CBR), overall survival, safety. Results: The trial accrued 73 patients (Stratum 1/2, 52/21) pts from August 2006 to March 2009. Seventy two pts (Stratum 1/2 52/20) were treated. As of April 5, 2010, two pts (both stratum 1) remained on treatment. The most common grade 3-4 adverse event in each stratum was fatigue (Stratum 1/2 11.5%/10%). Incidence of grade 3 hypertension (Stratum 1/2) was 3.8%/5.0%. No treatment-related deaths, colonic perforations or clinical CHF events occurred. The median number of cycles of docetaxel delivered was 8 in both strata. The median number of cycles of Bev delivered was 8 in stratum 1 and 12.5 in stratum 2. The median number of cycles of trastuzumab delivered in stratum 2 was 13. The ORRs were 57.7% (5.8% CR, 51.9% PR) in stratum 1, and 81.0% (28.6% CR, 52.4% PR) in stratum 2. The CBRs were 67.3% (95% C.I., 52.9%-79.7%) in stratum 1, and 81.0% (95% C.I., 58.1%-94.6%) in stratum 2. The median (95% CI) PFS was 8.5 (5.33-10.77) months in stratum 1 and 13.43 (12.10-N.A.) months in stratum 2. Conclusion: In first-line MBC, docetaxel of 75 mg/m 2 plus Bev administered Q3W in HER2- and of docetaxel and trastuzumab plus Bev in HER2+ disease is feasible and safe in the community practice setting, with high response rates and promising PFS compared to historical controls not treated with Bev. The tolerability of docetaxel 75 mg/m 2 with Bev may be better than higher dose docetaxel. These results support the use of these regimens in the clinical practice setting. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-12-08.