Skeletal-related events (SREs) in patients with bone metastases are associated with increased pain and analgesic use, according to a new analysis of three phase III trials. The results suggest that treatments to prevent SREs could decrease pain and opioid intake in these patients.
“Advances in cancer treatments and earlier diagnosis have extended survival; patients with breast and prostate cancers live an average of 2 to 3 years after a diagnosis of bone metastasis,” wrote study authors led by Roger von Moos, MD, of Kantonsspital Graubünden in Switzerland. “However, extending survival also prolongs the course of the disease and its associated sequelae. Therefore, managing the symptoms of bone metastasis has become an important goal of therapy.”
In the new study, the researchers pooled data from three identically designed phase III trials comparing denosumab and zoledronic acid in bone metastasis patients. In total, the analysis included 5,543 patients; of these, 1,925 had an on-study SRE, and 3,618 did not. SREs included pathological fracture, radiation to bone, surgery to bone, and spinal cord compression. The results were published online ahead of print in Supportive Care in Cancer.
Among those with an on-study SRE, the proportion of those with moderate or severe pain increased in the 6 months prior to the SRE. Both pain and analgesic use were most increased following spinal cord compression.
Each individual type of SRE was significantly associated with progression from no/mild pain at baseline to moderate or severe pain. For pathologic fracture, the hazard ratio (HR) for progressing to the more severe pain group was 1.29 (95% confidence interval [CI], 1.07–1.57; P = .0087). For radiation to bone, it was 2.51 (95% CI, 2.03–3.10; P < .0001). For surgery to bone, it was 2.75 (95% CI, 1.19–6.33; P = .0177). And for spinal cord compression, the HR was 3.07 (95% CI, 1.83–5.13; P < .0001).
Results were similar for progression from no or low opioid use at baseline to strong opioid use.
There was also a shorter median time to a clinically meaningful increase (two points or greater) from baseline in pain interference for patients with any SRE, assessed using the Brief Pain Inventory Short Form. The median time for those with an on-study SRE was 9.5 months, compared with 10.4 months for those without an SRE, for an HR of 1.19 (95% CI, 1.09–1.29; P < .0001). Spinal cord compression was associated with the highest risk of clinically meaningful worsening in overall pain interference.
“By preventing SREs, bone-targeted agents such as denosumab or bisphosphonates may delay pain worsening, help patients avoid the need for increased analgesic use, and thus reduce the burden of SREs on daily functioning,” the authors concluded.