Cabozantinib in Chemotherapy-Pretreated Metastatic CRPC: Interim Results from a Phase 2 Non-Randomized Expansion Cohort
The interim results reported today include data from 93 men enrolled in the ongoing non-randomized expansion (NRE) 100 mg cohort of the company’s phase 2 randomized discontinuation trial. All patients had bone metastases on bone scan and 46% had measurable soft tissue disease. All patients had received prior docetaxel, 35% had prior abiraterone or MDV3100, and 24% had received prior cabazitaxel. Bone directed therapies such as zoledronic acid, denosumab and alpharadin were used in 57%, 14% and 1% of patients, respectively. Seventy-three percent of patients had received at least 2 prior lines of therapy for CRPC. Clinically significant pain, defined as baseline pain score by Brief Pain Inventory (BPI) ≥4, was present in 44% of patients, with the majority requiring chronic narcotic administration.
Bone Scan Response (BSR). Computer-assisted evaluation of bone scan lesion area (BSLA) was determined by an Independent Radiology Committee (IRC) and showed an overall BSR rate (complete response + partial response) of 67%. Another 16% of patients had stable disease and 8% had a best response of progressive disease. Median best BSLA change was a reduction of 60%, and reductions were observed in patients with prior abiraterone, MDV3100, cabazitaxel, and/or radionuclide therapy. The median duration of bone scan response was 5.4 months (range 5.0 – 6.9 months).
Pain Palliation. In 39 patients with clinically significant baseline pain, the median maximal reduction in pain from baseline was 46%. A clinically significant reduction of pain, defined as a ≥30% decrease in pain score, was observed in 25 patients (64%). Fifty-six percent of patients decreased their use of narcotics, including 31% who discontinued narcotics. These improvements were observed in patients with a variety of prior therapies.
Circulating Tumor Cells. Robust reductions in circulating tumor cells (CTCs) were observed regardless of prior therapy in 62 patients with baseline CTC counts ≥5/7.5 mL of blood and a week 6 and/or week 12 assessment. Fifty-seven patients (92%) had ≥30% decrease in their CTC count. Thirty-nine percent of evaluable patients converted to
The 2012 NRE mCRPC
An exploratory analysis of bone scan lesion area (BSLA), circulating tumor cell (CTC) change, pain reduction, and overall survival (OS) in patients (pts) with castration-resistant prostate cancer (CRPC) treated with cabozantinib (cabo): Updated results of a phase II nonrandomized expansion (NRE) cohort. (Abstract 5026)
Howard I. Scher