P4-13-01: Pain Severity and Analgesic Use Associated with Skeletal-Related Events in Patients with Advanced Breast Cancer and Bone Metastases.
Authors: Fallowfield L , Cleeland CS , Body J-J , Stopeck A , von Moos R , Patrick DL , Clemons M , Tonkin K , Masuda N , Lipton A , De Boer R , Salvagni S , Tosello Oliveira C , Ying W , Braun A , Cong Z 
Published: June 2012

Abstract
Background: Skeletal-related events (SREs), which include pathologic fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC), occur frequently in patients with bone metastases and can lead to debilitating clinical consequences such as functional impairment and bone pain. Denosumab (XGEVA®) is a fully human monoclonal antibody against RANKL, shown to be superior to zoledronic acid (ZA; Zometa®) for the prevention of SREs in patients with solid tumors. Denosumab also delayed the onset of moderate or severe pain compared with ZA. The pain severity and analgesic use associated with each type of SRE were assessed in patients with advanced breast cancer and bone metastases.
Methods: Eligible patients received denosumab 120 mg SC or ZA 4 mg (adjusted for renal function) IV every 4 weeks in a randomized, multinational, double-blind, double-dummy trial. Patient-reported pain was assessed with the Brief Pain Inventory (BPI; 0 no pain to 10 severe pain) at baseline (BL) and at each monthly visit. Opioid and non-opioid analgesic use was recorded and scored using the Analgesic Quantification Algorithm (AQA; 0 no analgesic use to 7 &gt; 600mg oral morphine equivalent/day). Data from the two treatment arms were pooled for this analysis. Pain and analgesic use were evaluated from 6 months prior to and 6 months after the first on-study SRE for each patient. The comparator group included patients without an SRE and was centered at the median time from randomization to first SRE by SRE type, with corresponding 12 month assessments. The proportion of patients with moderate/severe pain (BPI worst pain score &gt; 4) and proportion of patients shifting from no/low analgesic use (AQA ≤ 2) at baseline to strong opioid use (AQA ≥ 3) were reported by month and by SRE type, and are summarized by mean relative change (%) across the time period.
Results: In total, 687 patients with first on-study SRE occurrences (PF=450, RB=201, SCC=16, SB=20) were analyzed. A similar proportion of patients with and without a PF had moderate/severe pain, but a higher proportion of patients with a PF shifted from no/low analgesic use to strong opioid use (mean relative increase 80%). Starting 3 months prior to the event, more patients with RB than those without had moderate/severe pain (27% mean relative increase) and shifted from no/low analgesic use to strong opioid use (mean relative increase 269%). Similar pain and analgesic use patterns were noted for patients with SCC (mean relative increase in pain: 63%; in AQA shift: 913%). More patients with SB than those without had moderate/severe pain in the 6 months leading on to SB (mean relative increase 51%). The difference was attenuated after SB, but during this time a much higher proportion of patients with SB shifted from no/mild opioid use to strong opioid use (mean relative increase 220%).
Discussion: SREs are associated with increased pain severity and analgesic use in patients with advanced breast cancer and bone metastasis. Patterns of pain severity and analgesic use differed by SRE type. Effective treatments to prevent SREs can decrease pain and the need for treatment with opioid analgesics.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-13-01.