A phase II study evaluating clinical benefits of Abraxane? (Nab-Paclitaxel, Celgene) plus gemcitabine (Gemzar?, Eli Lily & Co) and bevacizumab (Avastin?, Genentech/Roche) as a first-line treatment in patients with metastatic breast cancer achieved primary endpoint with an 81% progression free survival rate at 6 months.
The results of the investigator-initiated phase II study were presented at the 47th annual meeting of the American Society of Clinical Oncology in Chicago, IL.
In the study, patients eligible for first-line chemotherapy were given Abraxane (125 mg/m2), followed by gemcitabine (1000 mg/m2) on days 1 and 8, followed by bevacizumab (15 mg/kg) on day 1 of each 21 day cycle. Forty-eight patients were evaluable for the study.
Metastatic breast cancer is a complex multi-step process involving the expansion of cancerous cells from the breast to other areas of the body. It is a serious complication of breast cancer, as metastatic disease in breast cancer is often fatal, with treatments mainly limited to palliation.
Breast cancer primarily metastasizes to the bone, lungs, regional lymph nodes, liver and to the brain, with the most common site being the bone. The typical environmental barriers in any metastatic event would include physical (basement membrane), chemical (Reactive oxygen species (ROS), hypoxia and low PH) and biological (immune surveillance, inhibitory cytokines and regulatory Extracellular Matrix (ECM) peptides) components. Organ-specific anatomic considerations can also influence metastasis; these include blood flow patterns from the primary tumor and the homing ability of cancer cells for certain tissues. The targeting by cancer cells of specific organs is likely regulated by chemoattractant factors and adhesion molecules, which are produced by the target organ along with the cell-surface receptors expressed by the tumor cells.
Study results
At a median follow-up of 10.6 months, the 6-month progression free survival rate was 81% (95% CI; 67%-91%). Median PFS was 11.7 months (95% CI: 8.7-13.1) and the median overall survival rate had not been reached. The 12-month overall survival rate was 84% (95% CI: 73%-97%). The confirmed complete response (CR) plus partial response (PR) rate was 69%, with two patients achieving CR and 31 achieving PR. The median duration of response was 9.9 months (95% CI: 7.3-12.6).
Grade 3 and higher adverse events occurred in 90% of patients in the study, with myelosuppression being the major toxicity experienced (75% grade 3 or higher).
