Cabozantinib Effective Against Bone Mets

Cabozantinib is a VEGFR inhibitor that prevents blood supply to the tumour and combats bone metastases. Clinical trials have now shown that a low dose of 40 mg of Cabozantinib is still effective in combatting metastatic prostate cancer.

The ultimate combination of Cabozantinib with Zytiga offers a powerful approach to the treatment of metastatic prostate cancer.

Results have been released from a clinical trial of 51 patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases receiving a 40 mg daily dose of cabozantinib (XL-184). The data suggests that the 40 mg daily dose has similar clinical activity to the 100 mg daily dose previously reported from this trial. The key parameters used included measurement of reduction of metastatic bone disease and soft tissue disease, and reduction of bone-related pain and narcotic use, with apparent improvement in adverse event rates and tolerability at the lower dose.

Professor Johann de Bono, M.D., Ph.D., leader of the prostate cancer targeted therapy team at The Institute of Cancer Research, London, and honorary consultant at The Royal Marsden Hospital presented the data today in an oral presentation session on prostate cancer at the European Society for Medical Oncology (ESMO) 2012 Annual Meeting in Vienna, Austria.

"The results presented today at ESMO are consistent with interim data previously reported for the 40 mg cohort of an ongoing investigator-sponsored trial evaluating low-dose cabozantinib in men with CRPC and bone metastases," said Dr Michael Morrissey, Ph.D., president and chief executive officer of Exelixis. "The data suggest that the 40 mg daily dose has activity with respect to a number of key metrics, including bone and soft tissue responses, as well as changes in pain scores and narcotic use. Additionally, the 40 mg daily dose appears to be well-tolerated in patients with metastatic CRPC."

The interim results reported today include data from 51 men enrolled in the 40 mg cohort of an ongoing phase 2 randomized trial. All patients had bone metastases on bone scan and 41% had measurable soft tissue disease. All patients had received prior docetaxel, 67% had received prior abiraterone or enzalutamide (MDV3100), and 25% had received prior cabazitaxel. Seventy-one percent of patients had received at least 2 prior lines of therapy for CRPC. Bone Scan Response (BSR). Computer-assisted evaluation of bone scan lesion area (BSLA) was performed and response evaluated by an Independent Radiology Committee (IRC). An overall BSR rate of 49% was observed, with another 29% of patients having stable disease, and 14% having a best response of progressive disease.

Initial results from ongoing efforts focused on documenting the direct impact of cabozantinib on tumor lesions in the bone of prostate cancer patients were presented, and suggest that cabozantinib's effects on bone scan may be linked to induction of tumor necrosis in bone metastases. In a patient with complete resolution of pelvic metastatic lesions on bone scan, diffusion-weighted magnetic resonance imaging (MRI) findings were consistent with tumor necrosis occurring within the bone metastases. Additional evidence for the tumor selective effect of cabozantinib on bone scans was also presented, based on an analysis of a patient with concurrent osteoarthritis. In this patient, near complete resolution of bone scan tracer uptake at sites of metastatic tumor lesions was observed, while bone scan tracer uptake was maintained at sites of osteoarthritis. To gain further insights into the effects of cabozantinib on bone lesions, there are other ongoing clinical trials using MRI, other imaging techniques, and bone-metastatic tumor biopsies.
Soft Tissue Response. Twenty-one patients had measurable soft tissue or visceral lesions at baseline and 19 patients had at least one post-baseline assessment. Evidence of tumor regression was seen in 79% of the 19 patients with at least one post-baseline assessment. Overall response by RECIST among 21 patients with at least baseline data was partial response in 10%, stable disease in 71%, and progressive disease in 10%. Soft tissue responses were independent of prior therapy.