Abstract P1-13-01: Comparing the Effects of Denosumab and Zoledronic Acid on Pain Interference with Daily Functioning in a Randomized Phase 3 Trial of Patients with Breast Cancer and Bone Metastases

Abstract

Abstract In a recently completed trial of breast cancer patients with bone metastases, denosumab, a fully human monoclonal anti-RANKL antibody, was superior to zoledronic acid (ZA) in delaying/preventing skeletal-related events. Between-treatment differences in patient-reported pain interference with daily functioning were assessed. Eligible breast cancer patients received monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg (double-bind, double-dummy design). Patients completed the Brief Pain Inventory (BPI) to assess pain severity and interference with daily functioning (range 0 [does not interfere]-10 [interferes completely]) at baseline (BL), day 8, and before each monthly visit through end of study. The BPI interference scale generated a total interference score as well as an activity subscale (interference with walking, general activity, and work) and an affective subscale (interference with relations with others, enjoyment of life, and mood). Analyses were conducted on all randomized patients with ≥1 PRO assessment and were performed through week 73, when 30% of patients had dropped out due to death, disease progression, or consent withdrawal. Subgroups included patients with no/mild and moderate/severe worst pain at BL. Analyses included time to improvement (≥2-point decrease) or worsening (≥2-point increase) in pain interference, mean change from baseline, and proportion of patients with improving or worsening pain interference scores. Time to improvement in pain interference with activity (PIWA) tended to occur more quickly with denosumab compared with ZA (N=1124; median: 70 days denosumab v 86 days ZA; P=0.09), and time to worsening PIWA tended to be longer with denosumab compared with ZA (N=1676; median: 394 days denosumab v 310 days ZA; P=0.13). In patients with no/mild pain at BL, denosumab also demonstrated a trend for shorter time to improvement in PIWA (N=388; 93 days denosumab v 120 days ZA; P=0.06) and longer time to worsening PIWA (N=755; 369 days denosumab v 232 days ZA; P=0.12). Overall, a greater proportion of patients on denosumab had improvement in PIWA on study than ZA (Figure). Findings were similar with the total interference score and affective subscale. Figure Proportion of Patients With Improvement in Pain Interference With Activity (≥2-point decrease from BL)* Daily functioning (total interference and interference with activity and affect) tended to be less disrupted by pain in patients on denosumab compared with ZA. Decreased pain interference showed a trend to occur more quickly with denosumab. Overall, a greater proportion of denosumab patients reported decreased pain interference than ZA patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-01.