Evan Y Yu1, Fenghai Duan2, Mark Muzi3, Xuan Deng2, Bennett B Chin4, Joshi J Alumkal5, Mary-Ellen Taplin6, Jina M Taub3, Ben Herman2, Celestia S Higano3, Robert K Doot7, Donna Hartfeil8, Philip G Febbo9, David A Mankoff7. 1. University of Washington, Seattle, Washington evanyu@uw.edu. 2. Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island. 3. University of Washington, Seattle, Washington. 4. Duke University, Durham, North Carolina. 5. Oregon Health & Science University, Portland, Oregon. 6. Dana-Farber Cancer Institute, Boston, Massachusetts. 7. University of Pennsylvania, Philadelphia, Pennsylvania. 8. American College of Radiology Imaging Network (ACRIN), Philadelphia, Pennsylvania; and. 9. University of California San Francisco, San Francisco, California.
Abstract
UNLABELLED: (18)F-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone. METHODS: This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent (18)F-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in (18)F-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between (18)F-fluoride incorporation in tumor and normal bone, (18)F-fluoride transport in bone metastases, correlation with progression-free survival (PFS), prostate-specific antigen, and markers of bone turnover. RESULTS: Eighteen participants enrolled, and 17 underwent interpretable baseline (18)F-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential (18)F-fluoride PET response between tumor and normal bone (P < 0.0001). Changes in (18)F-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82-1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostate-specific antigen (P = 0.47). CONCLUSION: This trial provides evidence of the ability (18)F-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.
UNLABELLED: (18)F-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone. METHODS: This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent (18)F-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in (18)F-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between (18)F-fluoride incorporation in tumor and normal bone, (18)F-fluoride transport in bone metastases, correlation with progression-free survival (PFS), prostate-specific antigen, and markers of bone turnover. RESULTS: Eighteen participants enrolled, and 17 underwent interpretable baseline (18)F-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential (18)F-fluoride PET response between tumor and normal bone (P < 0.0001). Changes in (18)F-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82-1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostate-specific antigen (P = 0.47). CONCLUSION: This trial provides evidence of the ability (18)F-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.
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