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Randomized Controlled Trial
. 2016 Mar;24(3):1327-37.
doi: 10.1007/s00520-015-2908-1. Epub 2015 Sep 2.

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

Roger von Moos  1 , Jean-Jacques Body  2 , Blair Egerdie  3 , Alison Stopeck  4 , Janet Brown  5 , Lesley Fallowfield  6 , Donald L Patrick  7 , Charles Cleeland  8 , Danail Damyanov  9 , Felipe Salvador Palazzo  10 , Gavin Marx  11 , Ying Zhou  12 , Ada Braun  12 , Arun Balakumaran  12 , Yi Qian  12
Affiliations
Randomized Controlled Trial

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

Roger von Moos et al. Support Care Cancer. 2016 Mar.

Abstract

Purpose: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning.

Methods: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm.

Results: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function.

Conclusions: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning.

Keywords: Analgesic Quantification Algorithm (AQA); Brief Pain Inventory (BPI); Denosumab; Pain; Skeletal-related events (SREs); Zoledronic acid.

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Figures

Fig. 1
Fig. 1
Proportion of patients with moderate/severe pain and strong opioid use. Moderate/severe pain is a BPI-SF worst pain score >4. Strong opioid use is an AQA score ≥3. Study visit −6 represents the visit 6 months before the occurrence of the first on-study SRE. The dashed vertical line represents the occurrence of the first SRE. Study visit 1 represents the first visit after the SRE. For patients with no SRE, data were not consistently available for months −6, −5, and −4. AQA Analgesic Quantification Algorithm, BPI-SF Brief Pain Inventory Short Form, SRE skeletal-related event
Fig. 2
Fig. 2
a Risk of progressing to moderate/severe pain and strong opioid use. Includes patients with baseline pain score ≤4 (pain progression; N = 2683 or AQA score ≤2) (opioid use; N = 4340); percentages indicate relative risk increase. *P < 005; **P < 0.01; ***P < 0.0001. b Risk of clinically meaningful worsening (≥2-point increase) from baseline in pain interference. Data include patients with baseline pain interference scores ≤8; percentages indicate relative risk increase. **P < 0.01; ***P ≤ 0.0001. AQA Analgesic Quantification Algorithm, CI confidence interval, SRE skeletal-related event
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