Despite the availability of multiple treatment options for women with breast cancer, including surgery, radiation, hormonal therapy, and cytotoxic agents, there is still a significant unmet medical need for new treatment options. Hormonal therapy is the main option for patients with hormone receptor-positive breast cancer, although resistance to this treatment is often associated with ligand-independent activation of the estrogen receptor. Several studies have implicated MET, VEGFR2, and RET, targets of cabozantinib, in the onset, progression, metastasis, and recurrence of breast cancer.

The phase 2 randomized discontinuation trial of cabozantinib included 20 women with measurable metastatic breast cancer (ASCO 2011). Despite the typically poor prognosis of these patients, 2 of 20 experienced a partial response and 15 of 20 patients had tumor shrinkage as their best response with cabozantinib treatment. The responders had hormone receptor-positive disease. Three patients had baseline and on-treatment bone scans. Two of these patients had partial resolution of their lesions on bone scan, which was associated with a decrease in pain. The third patient had stable disease on bone scan.

Metastatic bone lesions from cancer as imaged on bone scan, FDG-PET scan or X-ray are not considered 'measurable' by the RECIST criteria. As a result, patients with bone-only or bone-predominant metastatic breast cancer without measurable disease have typically been excluded from clinical trials that include response measurements as a primary endpoint. However, such patients are common in the breast clinic and there is an unmet need to evaluate novel agents that may effectively treat their metastatic disease burden in bone as well as soft tissue sites.

The Significance of Bone Metastases in Metastatic Breast Cancer

Overall, bone is the most common site to which breast cancer metastasizes, and the site of first metastasis in approximately 50% of patients with breast cancer. Up to 75% of patients with metastatic breast cancer will develop bone metastases during the course of their disease and this number is even higher among those with hormone receptor-positive disease. For 20-25% of patients with metastatic breast cancer, especially those with hormone receptor-positive disease, bone will be their only site of metastatic involvement. Bone metastases in women with breast cancer are associated with considerable morbidity including hypercalcemia, increased fracture risk, need for surgery or radiotherapy, and spinal cord compression.

Source Exelixis, Inc.