An Exploratory Analysis Of The Role Of Dasatinib In Preventing Progression Of Disease In Bone In Patients With Metastatic Breast Cancer

Introduction: The role of dasatinib, an oral SRC inhibitor is being explored for the treatment of metastatic breast cancer. In a phase I study, we previously established that the combination of dasatinib and weekly paclitaxel was feasible. The activity of this combination is currently being explored in an ongoing phase II trial. Since Src kinase has a major role in osteoclast function and dasatinib has established anabolic and anti-resorptive effects in bone in vitro, we hypothesized that patients receiving this combination would have good control of osseous metastases and primarily develop progression of disease in sites other than bone. Patients and methods: Patients were included in this analysis if they participated in the phase I or II metastatic breast cancer studies and received dasatinib at or above the recommended phase II dose of 120mg with paclitaxel (80mg/m2 day 1 and 8 of each 21day cycle). Patients who discontinued therapy for reasons other than progression were excluded. Per protocol, patients were required to discontinue bisphosphonates or other bone modulating agents for the first 8 weeks of study due to the potential for hypocalcaemia. Thereafter, they were permitted to receive these agents at the discretion of their treating physician. Patients provided serum samples for correlative studies. Assessment of N-telopeptide of type 1 collagen (NTX), a product of mature bone collagen that reflects bone specific resorption, is planned. Results: The median age of the 24 patients who met criteria for analysis was 50y (37 - 66y). Of these, 15 (63%) had ER+ disease, and 24 (100%) were negative for human epidermal growth factor receptor (HER2). At study entry, 17 (71%) patients had bone involvement. Following the initial eight week moratorium, 7 (29%) patients received a bisphosphonate or rank ligand inhibitor during treatment with dasatinib + paclitaxel. Patients received a median 2 months (range 1-23) of dasatinib + paclitaxel therapy. To date, 3 (13%) continue on therapy, and 21 (88%) have had progression of disease. Among patients who progressed, 18 (86%) have progressed in visceral sites and only 3 (14%) progressed in bone. Analyses of serum NTX levels are ongoing and will be compared by site of progression. Conclusion: The potential role of serum NTX as a predictive biomarker of benefit from dasatinib and paclitaxel is being explored and updated results will be presented. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-12.