Risk Factors For Bone Pain Among Patients Receiving Myelosuppressive Chemotherapy and Primary Prophylactic Pegfilgrastim

Febrile neutropenia (FN) is a common, life-threatening side effect of myelosuppressive chemotherapy. Prophylactic pegfilgrastim (Neulasta) beginning with the first cycle of chemotherapy has been shown to reduce the incidence of FN (Vogel CL et al., J Clin Oncol., 2005). Bone pain is the most common adverse event associated with pegfilgrastim, and most incidences of bone pain can be managed with nonsteroidal anti-inflammatory drugs (NSAIDs). However, little is known about risk factors for bone pain in patients treated with pegfilgrastim.

This study used individual patient data from 23 Amgen-sponsored, randomized clinical trials and included adults receiving myelosuppressive chemotherapy and primary prophylactic pegfilgrastim. Bone pain was identified based on the adverse events reported in the trials. Multivariable logistic regression models were used to identify risk factors associated with the occurrence of moderate to severe bone pain (grade 2+) in cycle 1 (the primary outcome) and across cycles 1-6 and any grade bone pain in cycle 1 and across cycles 1-6. Data collected in the trials and included in the regression model include baseline patient characteristics (gender, race, and age); disease characteristics (primary tumor type and tumor stage); treatment characteristics (taxane vs no taxane treatment and dose of pegfilgrastim); and medical history (osteoporosis/osteopenia, hypercholesterolemia, anemia, neutropenia, osteomyelitis/osteonecrosis, arthritis, peripheral neuropathy, chronic fatigue syndrome, gout, bone fracture, and bone pain).

This study included data from 1974 patients who received myelosuppressive chemotherapy and primary prophylactic pegfilgrastim. The most frequent tumor types in the study sample were breast cancer (54.8%), non-small cell lung cancer (17.1%), and non-Hodgkins lymphoma (13.6%). 41.2% of patients had stage IV disease. Grade 2+ bone pain was reported in 372 patients (18.8%) in cycle 1 and 564 patients (28.6%) across the first 6 cycles, while any grade bone pain was reported in 709 patients (35.9%) in cycle 1 and 1016 patients (51.5%) across the first 6 cycles. In the first cycle of chemotherapy, previous history of osteoporosis/osteopenia (odds ratio [OR] 1.28; 95% CI 1.04-1.56), gout (1.44; 0.98-2.13), and bone pain (1.28; 1.09-1.49), and pegfilgrastim dose (100 mcg/kg vs a fixed dose of 6 mg; 1.68; 1.13-2.51) were associated with increased risk of grade 2+ bone pain; compared with breast cancer, colorectal cancer was associated with reduced risk of grade 2+ bone pain (0.26; 0.11-0.60) and ovarian cancer with increased risk of grade 2+ bone pain (1.89; 0.98-3.64); compared with age <45 years, age ≥65 years was associated with reduced risk of grade 2+ bone pain (0.80; 0.63-1.01) (table).

History of osteoporosis/osteopenia, history of bone pain, breast cancer (vs colorectal cancer), and younger age appear to be risk factors for bone pain in chemotherapy-treated patients who received primary prophylactic pegfilgrastim. The study results may be used to identify patients at increased risk of bone pain who may benefit from pain therapy.

Xu: Amgen Inc. : Employment, Equity Ownership. Gong:Amgen Inc. : Employment, Equity Ownership. Vogl:Amgen Inc. : Employment, Equity Ownership. Abella:Amgen Inc. : Employment. Page:Amgen Inc. : Employment, Equity Ownership.