Impact of skeletal-related events on pain and analgesic use in patients with solid tumors and bone metastases.

Abstract

e20514 Background: Skeletal-related events (SREs) including pathological fracture (PF), surgery (SB) or radiotherapy to bone (RB), or spinal cord compression (SCC) occur frequently in patients (pts) with advanced cancer and bone metastases and may cause debilitating clinical sequelae for pts. Pooled results from 3 clinical trials showed denosumab was superior to zoledronic acid (ZA) for prevention of SREs. We now evaluate the burden of SREs through pt-reported pain and analgesic use. Methods: Randomized (1:1) pts in the phase III, double-blind, placebo-controlled trials received denosumab (120 mg SC) or ZA (4 mg IV, adjusted for renal function) monthly. In this posthoc analysis, data from pts with solid tumors in the 2 treatment arms were pooled. At baseline (BL) and each monthly visit, pain was assessed via the Brief Pain Inventory (BPI; 0 no pain to 10 severe pain), and pts’ analgesic use with the Analgesic Quantification Algorithm (AQA; 0 no analgesics to 7 > 600 mg oral morphine equivalent/day). Pain and analgesic use for pts with SREs were assessed from 6 months before to 6 months after the 1st on-study SRE. A control group was comprised of all pts without SREs; the index time was defined as the median time to each SRE type. SRE impact was assessed using a stratified Cox proportional hazards model adjusting for SREs, as time-dependent covariates, and other baseline characteristics, and reported as HR and 95% CI. Results: 1,925 pts had an on-study SRE (first SRE type: 923 PF; 829 RB, 119 SCC, 54 SB), and 3,618 pts did not. A greater proportion of pts with SREs had a BPI worst pain score > 4 (moderate/severe pain) or an AQA score ≥ 3 (strong opioid use) than did pts with no SREs. The development of SRE was associated with significantly greater risk of pain progression from no/mild pain at BL to moderate/severe pain on study (PF 1.29 [1.07, 1.57], P = 0.009; RB 2.51 [2.03, 3.10], P < 0.001; SCC 3.07 [1.83, 5.13], P < 0.001; and SB 2.75 [1.19, 6.33], P = 0.018). Conclusions: Pts who experienced on-study SREs had increased pain severity requiring stronger analgesic use. Effective treatments that delay or prevent SREs can reduce pain and the need for palliation with opioids. Clinical trial information: NCT00321464, NCT00321620, and NCT00330759.