Abstract
BackgroundBone remodeling is disrupted in metastatic disease, which affects > 70% of metastatic castration-resistant prostate cancer (mCRPC) patients. As a result, abnormal levels of specific bone turnover biomarkers (BTMs) are released. In this prospective ancillary analysis of the Italian real-world study ABITUDE, four markers were measured during abiraterone acetate plus prednisone (AAP) treatment in chemotherapy-naïve mCRPC men failing androgen-deprivation therapy. MethodsPatients were enrolled if a blood sample was obtained before the first administration of abiraterone (baseline); ad-hoc blood samples were withdrawn during routine tests after 3, 6, and 12 months. A centralized lab measured bone alkaline phosphatase (BALP, osteoblast activity marker), type-I collagen-C-telopeptide (CTX-1, bone resorption marker), parathyroid hormone (PTH) and vitamin D (vitD). At each time point, intra-patient variations vs baseline were compared by the signed-rank test (statistical significance: P-value < 0.05). ResultsOf 481 patients enrolled in ABITUDE, 186 (median age: 76 [range: 53–93] years) met the substudy criteria: 74.7% had bone metastases, 11.8% were on bone-targeted therapies (BTT) and 14.0% on vitD supplementation. BALP decreased significantly at month 6 (P = 0.0010) and 12 (P < 0.0001) and CTX-1 at month 6 (P = 0.0028); PTH increased at month 3 (P < 0.0001); no significant difference in vitD levels was observed. Similar findings were observed in BTT-untreated patients. The reduction in BALP and CTX-1 levels was more pronounced in patients with than without bone metastases; in the latter group, no significant variation in BALP and CTX-1 levels was observed. ConclusionsAAP seems to exert an effect on the microenvironment of metastatic but not of normal bone, which likely contributes to its antitumoral activity.
Highlights
Bone remodeling is a dynamic process that ensures the maintenance of skeletal integrity [1]
The complex crosstalk with the microenvironment [2,3,4] leads to a ‘‘vicious cycle” that favors the growth of bone metastases, found in >90% of patients throughout the disease course [5] and in >70% of those with metastatic castration-resistant prostate cancer (PCa) [6], and culminating in substantial morbidity and mortality
Study design and patient population. This is an ancillary study of ABITUDE, a large Italian multicenter prospective cohort study evaluating the effectiveness of acetate plus prednisone (AAP) in CTnaïve metastatic castration-resistant prostate cancer (mCRPC) patients who had failed ADT and in whom CT was not clinically indicated
Summary
Bone remodeling is a dynamic process that ensures the maintenance of skeletal integrity [1]. Osteoblastic lesions frequently present an osteolytic pattern that may extend beyond the sites of metastases and is responsible for the occurrence of SREs. Bone remodeling is disrupted in metastatic disease, which affects > 70% of metastatic castration-resistant prostate cancer (mCRPC) patients. Abnormal levels of specific bone turnover biomarkers (BTMs) are released. In this prospective ancillary analysis of the Italian real-world study ABITUDE, four markers were measured during abiraterone acetate plus prednisone (AAP) treatment in chemotherapy-naïve mCRPC men failing androgen-deprivation therapy. BALP decreased significantly at month 6 (P = 0.0010) and 12 (P < 0.0001) and CTX-1 at month 6 (P = 0.0028); PTH increased at month 3 (P < 0.0001); no significant difference in vitD levels was observed.
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