Denosumab or zoledronic acid (ZA) therapy on pain interference and cancer-specific quality of life (CSQoL) in patients with castrate-resistant prostate cancer (CRPC) and bone metastases (BM).

Abstract

12 Background: Patients with castration-resistant prostate cancer (CRPC) and bone metastases (BM) may experience debilitating pain that impacts daily functioning and diminishes the quality of life. Previous results from a phase III trial demonstrated superiority of denosumab to ZA in delaying or preventing skeletal-related events (pathological fracture, radiation or surgery to the bone, spinal cord compression) in CRPC patients with BM. In this ad-hoc analysis, we present the results of denosumab or ZA therapy on pain interference (PI) and cancer specific quality of life (CSQoL), focusing on the subgroup of CRPC patients with no/mild pain at baseline. Methods: Men with CRPC and BM (no prior IV bisphosphonate use) were randomized to receive either SC denosumab 120 mg+IV placebo or SC placebo+IV ZA 4mg (adjusted for creatinine clearance) every four weeks. Patients were instructed to take calcium and vitamin D supplements. The Brief Pain Inventory–Short Form (BPI-SF) was used to assess PI. The pre-specified clinically meaningful time of a greater than or equal to two point increase from baseline in PI score (overall, physical, and emotional subdomains) was determined for CRPC patients receiving denosumab or ZA therapy. Patients also completed the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline and each monthly visit to determine CSQoL scores. Declining FACT-G scores points to worsening CSQoL, where a greater than or equal to five point decrease is clinically meaningful. Results: Of the 1,901 patients enrolled (n=950, denosumab; n=951, ZA), 1,045 (55%) had no/mild pain at baseline. Compared with ZA, denosumab therapy delayed the time to a greater than or equal to two point increase from baseline in PI for the overall score (HR=0.83 [0.71, 0.98]; P=0.023), physical (HR=0.87 [0.75, 1.02]; P=0.077) and emotional (HR=0.83 [0.71, 0.97]; P=0.020) subdomains. Over a period of 18 months, more ZA-treated patients than denosumab-treated patients experienced a greater than or equal to five point decrease in FACT-G total scores (average relative difference=6.8%, range -9.4 to 14.6%) or worsening of CSQoL. Conclusions: Denosumab therapy significantly delayed the time to worsening of pain interference and maintained a higher overall CSQoL (FACT-G) compared to ZA in CRPC patients with BM. Clinical trial information: NCT00321620.