Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study.

PURPOSE: Cabozantinib (XL184), a multi-targeted oral tyrosine kinase inhibitor with activity against MET, VEGFR2, AXL, and other tyrosine kinases, was assessed in a cohort of metastatic breast cancer (MBC) patients in a phase II randomized discontinuation trial (RDT). METHODS: Patients received 100 mg cabozantinib daily during a 12-week lead-in stage. Those with stable disease per modified Response Evaluation Criteria in Solid Tumors version 1.0 at 12 weeks were randomized to either continue cabozantinib or receive placebo. Primary endpoints were objective response rate (ORR) during the 12-week lead-in stage and progression-free survival (PFS) after randomization. Patients were also followed for overall survival (OS). RESULTS: Forty-five patients with MBC and a median of three prior lines of chemotherapy for metastatic disease were enrolled. The ORR during the lead-in stage was 13.6 % (95 % confidence interval [CI] 6-25.7 %), and the disease control rate at week 12 was 46.7 % (95 % CI 31.7-61.6 %). Per the initial RDT study design, patients with stable disease at week 12 were randomized to cabozantinib or placebo. Following a Study Oversight Committee recommendation, randomization was suspended. Patients in the lead-in stage continued on open-label cabozantinib. Patients in the randomization stage were subsequently unblinded. The overall median PFS for all MBC patients was 4.3 months. Median OS was 11.4 months (95 % CI 10.5-16.5 months). The most common grade 3/4 adverse events in the lead-in stage were palmar-plantar erythrodysesthesia (13 %) and fatigue (11 %). One death from respiratory failure was reported as drug-related during the lead-in stage. CONCLUSIONS: In heavily pretreated MBC patients, cabozantinib monotherapy demonstrated clinical activity including objective response and disease control.

The correlation between palliation of bone pain by intravenous strontium-89 and external beam radiation to linked field in patients with osteoblastic bone metastases.

We studied the correlation between the efficacy of local external beam radiotherapy and the efficacy of strontium-89 in the palliation of osteoblastic metastatic bone pain in 43 patients with cancer. All 43 had been treated with hormonal or chemotherapy according to the primary malignancies and analgetic pharmacotherapy as needed, 36 received local external beam radiotherapy as a palliative before strontium-89 injection, and all 43 were ultimately treated with strontium-89 as salvage therapy. Responses to the first strontium treatment, and to the first radiation treatment if given, were taken from patient files. Pain was evaluated by Karnofsky performance status, analgesic dosage, and duration of response to treatment translated into numeric scores on a pain duration scale and an integrated response scale. The efficacy of limited field external radiation in metastatic bone pain palliation was 80.6% versus 58.1% for strontium-89. Patients treated with both external radiation and strontium had a positive correlation of 0.4 with a probability of P = 0.0158 between the responses to the 2 treatments, indicating that response to external radiotherapy could be viewed as an indicator of strontium-89 efficacy in metastatic osteoblastic bone pain palliation in the same patient. No significant correlation was found between strontium efficacy and gender, location of metastases to weight-bearing bones, duration of hormonal therapy or chemotherapy, or type of primary neoplasm.