Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases.
OBJECTIVE
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.
Kantonsspital Graubünden, Loëstrasse 170, CH-7000, Chur, Switzerland. roger.vonmoos@ksgr.ch.
Roger
R
von Moos
CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
Jean-Jacques
JJ
Body
Urologic Medical Research, Kitchener, ON, Canada.
Blair
B
Egerdie
Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
Alison
A
Stopeck
Experimental Cancer Medicine Centre, Weston Park Hospital, University of Sheffield, Sheffield, UK.
Janet
J
Brown
University of Sussex, Brighton, UK.
Lesley
L
Fallowfield
University of Washington, Seattle, WA, USA.
Donald L
DL
Patrick
University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Charles
C
Cleeland
National Hospital for Treatment in Oncology, Sofia, Bulgaria.
Danail
D
Damyanov
Center for the Integral Assistance of Oncology Patients, San Miguel de Tucumán, Argentina.
Felipe Salvador
FS
Palazzo
Sydney Adventist Hospital, Wahroonga, Sydney, Australia.
Gavin
G
Marx
Amgen, Inc., Thousand Oaks, CA, USA.
Ying
Y
Zhou
Amgen, Inc., Thousand Oaks, CA, USA.
Ada
A
Braun
Amgen, Inc., Thousand Oaks, CA, USA.
Arun
A
Balakumaran
Amgen, Inc., Thousand Oaks, CA, USA.
Yi
Y
Qian
D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D000069448:Denosumab / Q000008:administration & dosage / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005598:Fractures, Spontaneous / Q000150:complications; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010146:Pain / Q000209:etiology*; D000077211:Zoledronic Acid
D000700:Analgesics; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid
Analgesic Quantification Algorithm (AQA); Brief Pain Inventory (BPI); Denosumab; Pain; Skeletal-related events (SREs); Zoledronic acid