Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer.

Autor:	Vaishampayan UN; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan. vaishamu@karmanos.org., Podgorski I; Department of Pharmacology and Oncology Wayne State University, Detroit, Michigan., Heilbrun LK; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan., Lawhorn-Crews JM; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan., Dobson KC; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan., Boerner J; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan., Stark K; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan., Smith DW; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan., Heath EI; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan., Fontana JA; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan., Shields AF; Department of Oncology Karmanos Cancer Center/Wayne State University, Detroit, Michigan.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2019 Jan 15; Vol. 25 (2), pp. 652-662. Date of Electronic Publication: 2018 Oct 16.
DOI:	10.1158/1078-0432.CCR-18-1473
Abstrakt:	Purpose: Cabozantinib is a multitargeted tyrosine kinase inhibitor that demonstrated remarkable responses on bone scan in metastatic prostate cancer. Randomized trials failed to demonstrate statistically significant overall survival (OS). We studied the dynamics of biomarker changes with imaging and biopsies pretherapy and posttherapy to explore factors that are likely to be predictive of efficacy with cabozantinib. Experimental Design: Eligibility included patients with metastatic castrate-resistant prostate cancer with normal organ function and performance status 0-2. Cabozantinib 60 mg orally was administered daily. Pretherapy and 2 weeks post, 99m Tc-labeled bone scans, positron emission tomography with 18 F-sodium fluoride (NaF-PET) and 18 F-(1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl) thymine (FMAU PET) scans were conducted. Pretherapy and posttherapy tumor biopsies were conducted, and serum and urine bone markers were measured. Results: Twenty evaluable patients were treated. Eight patients had a PSA decline, of which 2 had a decline of ≥50%. Median progression-free survival (PFS) and 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 who were clinically stable and remained 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. (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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