Biomarkers and Bone Imaging Dynamics associated with Clinical outcomes of Oral Cabozantinib Therapy in Metastatic Castrate Resistant Prostate Cancer

Background: Cabozantinib is a multitargeted tyrosine kinase inhibitor demonstrating remarkable responses in prostate cancer bone metastases . We studied the dynamics of biomarker changes with imaging, and biopsies pre- and post-therapy to explore factors that are likely to be predictive of efficacy with cabozantinib. Methods: Eligibility included metastatic castrate resistant prostate cancer patients with normal organ function and performance status 0-2. Cabozantinib 60 mg orally was administered daily. Pretherapy and 2 weeks post, ^99mTc-labeled bone scans (BS), positron emission tomography with ¹⁸F-sodium fluoride (NaF-PET) and ¹⁸F-(1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl) thymine (FMAU-PET) scans were conducted. Pre and post therapy tumor biopsies were conducted, and serum and urine bone markers were measured. Results: 20 evaluable pts were treated. 8 patients had a PSA decline, of which 2 had a decline ≥50%. Median progression free survival (PFS) and overall survival (OS) were 4.1 and 11.2 months, respectively and 3 patients were on therapy for 8, 10 and 13 months. The NaF-PET demonstrated a median decline in SUVmax of -56% (range -85 to -5%, n = 11) and -41% (range -60 to -25%, n = 9) for patients on therapy for ≥ 4 or < 4 cycles, respectively. The FMAU-PET demonstrated a median decline in SUVmax of -44% (-60 to -14%) and -42% (-63% to -23%) for these groups. The changes in bone markers and mesenchymal epithelial transition/MET testing did not correlate with clinical benefit. Conclusions: Early changes in imaging and tissue or serum/urine biomarkers did not demonstrate utility in predicting clinical benefit with cabozantinib therapy.

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