Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer.
BACKGROUND
Cabozantinib is active in advanced prostate cancer with improvement on bone scans in men on phase II trials. This trial evaluated the efficacy and changes in bone lesions in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib.


PATIENTS AND METHODS
Eligible patients with mCRPC involving bone underwent biopsy of a bone lesion followed by cabozantinib starting at 60 mg daily and continuing until progression or intolerable toxicity. The primary study endpoint was progression-free survival at 12 weeks. The bone lesion was rebiopsied at 6 weeks. Expression of CMET, phospho-CMET, and VEGFR2 was assayed by immunohistochemistry. Serum was obtained at baseline, and at 3, 6, and 12 weeks and assayed for bone remodeling markers.


RESULTS
A total of 25 patients were enrolled: 22 were evaluable, and 3 were excluded before receiving cabozantinib. At 12 weeks, 17 (77%) of 22 patients had stable disease or better. The median time on treatment was 24 weeks (range, 3-112 weeks). The overall median progression-free survival was 43.7 weeks (95% confidence interval, 23.7-97.0 weeks). Eight (36%) of 22 patients had markedly reduced uptake on bone scan. Patients with significant response on bone scan had higher bone morphogenic protein-2 levels at baseline, stable N-telopeptides levels, increased vascular endothelial growth factor receptor 2 expression, and a trend towards increased phospho-CMET while on cabozantinib compared with patients with stable disease.


CONCLUSIONS
Cabozantinib is active in men with mCRPC, inducing significant changes on bone scan in one-third of patients with changes in markers of bone formation and the tumor microenvironment.
['Smith|David C|DC|', 'Daignault-Newton|Stephanie|S|', 'Grivas|Petros|P|', 'Reichert|Zachery R|ZR|', 'Hussain|Maha|M|', 'Cooney|Kathleen A|KA|', 'Caram|Megan|M|', 'Alva|Ajjai|A|', 'Jacobson|Jon|J|', 'Yablon|Corrie|C|', 'Mehra|Rohit|R|', 'Escara-Wilke|June|J|', 'Shelley|Greg|G|', 'Keller|Evan T|ET|']
D000368:Aged D000813:Anilides D001859:Bone Neoplasms D005500:Follow-Up Studies D006801:Humans D008137:Longitudinal Studies D008297:Male D008875:Middle Aged D065228:Non-Randomized Controlled Trials as Topic D011379:Prognosis D064129:Prostatic Neoplasms, Castration-Resistant D011725:Pyridines D015996:Survival Rate
Markers of bone metabolism