Abstract B114: Cabozantinib effects on bone metastasis: Computer-aided quantitative bone scan assessment of prostate cancer treatment response.

Abstract

Abstract Background: Cabozantinib is an oral inhibitor of MET and VEGFR2 and at a dose of 100 mg qd has demonstrated high rates of partial or complete bone scan resolution in CRPC patients with bone metastases, as assessed by manual visual reads. No accepted approach exists for the assessment of bone scan response in prostate cancer patients. An FDA 510(k) approved image analysis package has been developed that includes a computer-aided detection (CAD) system to detect pixels associated with bone lesions on bone scan with high accuracy, thus facilitating quantitative assessment of tumor burden with advantages of objectivity and consistency over manual approaches. A change in total Bone Scan Lesion Area of 30% or greater has been previously established as a cutoff point to distinguish responders from non-responders [1]. Methods: Original Digital Imaging and Communications in Medicine (DICOM) format images of baseline and week 6 bone scan assessments were collected and analyzed by the automated CAD system then reviewed by a physician experienced with bone scan interpretation as part of an ongoing clinical study of single agent cabozantinib at a lower starting dose of 40 mg qd in CRPC subjects with evidence of bone metastases. All subjects had undergone standard of care whole body scintigraphy, 2–4 hours post-injection of 20–25 mCi of Tc MDP. All images underwent intensity normalization to a bone scan reference to account for differences in radiotracer dosing levels and scan timing to improve reproducibility. Lesions consistent with metastatic foci of disease were automatically segmented based on anatomic region-specific intensity thresholds. Each segmented image was reviewed by a nuclear medicine physician for removal of any remaining false positive regions (e.g. areas of degenerative joint disease). Quantitative assessment of lesion burden was then determined. Results: 10 CRPC subjects showing evidence of bone metastasis were treated in an ongoing dose-ranging study with cabozantinib and were evaluable for bone scan response assessment at week 6. Reductions in the following parameters (median and range) were observed at week 6 relative to baseline: total Bone Scan Lesion Area (168.5 cm2 [20, 864] to 54 cm2 [0, 431]; 68% reduction), Bone Scan Lesion Count (34 [3, 74] to 3 [0, 64]; 91% reduction), and mean normalized Bone Scan Lesion Intensity (92.2 [56.5, 155.0] to 57.0 [0, 90.5]; 38% reduction). All 10 subjects had a reduction in Bone Scan Lesion Area, with 9 achieving a bone scan response at the week 6 timepoint as assessed by both the CAD system and visual review by the investigator. Conclusion: A significant reduction in apparent bone scan abnormality was demonstrated by the automated CAD system. The results demonstrate the potential for objective measurement of cabozantinib treatment effects in bone, laying the foundation for further validation against other clinically relevant outcome measures such as pain and overall survival. Reference: 1. G. H. Chu, M. S. Brown, H. J. Kim, M. Auerbach, C. Poon, B. Ramakrishna, A. Vidovic, D. W. Gjertson, M. J. Morris, S. M. Larson, J. G. Goldin, H. I. Scher. Initial analytic validation of automated bone scan measures for treatment response assessment in patients with metastatic castration-resistant prostate cancer (CRPC). J Clin Oncol 29: 2011 (suppl; abstr e15174). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B114.