Reported Bone Pain in Cancer Patients Receiving Chemotherapy in Pegfilgrastim Clinical Trials: A Retrospective Analysis.

Abstract Abstract 4561 Background Mild to moderate bone pain is the most commonly reported treatment-related adverse event (AE) associated with administration of granulocyte colony-stimulating factors (G-CSFs). There is a perception that bone pain associated with pegfilgrastim (the pegylated form of filgrastim) occurs at a higher frequency, is more severe, and is less predictable than bone pain associated with filgrastim. To evaluate this hypothesis, a retrospective analysis examining bone pain in cancer patients receiving chemotherapy in pegfilgrastim clinical trials was conducted. Methods Data analyzed were from 12 sponsor-supported trials of once per chemotherapy cycle pegfilgrastim (6 mg fixed dose or 100 mcg/kg) versus daily filgrastim (5 mcg/kg) or versus no G-CSF administered following chemotherapy in patients with non-Hodgkin's lymphoma (NHL), breast, lung, colorectal, or ovarian cancer. The AEs reported were coded according to MedDRA (version 11) and the preferred terms considered to include bone pain were determined prior to analysis. Incidences of any grade and grade 3/4 bone pain were calculated by treatment (pegfilgrastim, filgrastim, or no G-CSF) and chemotherapy cycle. Results Data for patients who received pegfilgrastim (n=1498), filgrastim (n=354) or no G-CSF (n=1102) were included in this analysis. In the 7 studies comparing pegfilgrastim (n=377) with filgrastim (n=354) in patients with NHL, breast or lung cancer, similar proportions of patients reported bone pain of any grade (Table 1). In both treatment arms, bone pain incidence was highest in the first cycle of chemotherapy and decreased in subsequent cycles. In both the pegfilgrastim and filgrastim arms, grade 3/4 bone pain incidence was low across all cycles (6.6% and 7.9%, respectively), in the first cycle (4.2% and 5.4%, respectively), and in subsequent cycles (Table 1). In the 5 studies comparing pegfilgrastim (n=1121) with no G-CSF (n=1102) in patients with NHL, breast, lung, colorectal, or ovarian cancer, 74% of the patients were female, 78% were white and the median (minimum, maximum) age was 65 (18, 88) years. Of these patients, 53% had breast cancer and 68% received a taxane-based regimen. Three of the 5 studies allowed pegfilgrastim use after cycle 1 in the control arm (ie, secondary prophylaxis); therefore, only cycle 1 bone pain incidences were compared for this analysis. The proportion (confidence interval [CI]) of patients who reported bone pain in the first cycle of chemotherapy was higher in the pegfilgrastim arm than the no G-CSF arm; 32.7% (30.0%, 35.6%) versus 23.0% (20.6%, 25.7%). Grade 3/4 bone pain was infrequently reported in these patients (3.4% [2.4%, 4.6%] pegfilgrastim, 2.0% [1.3%, 3.0%] no G-CSF). Conclusions In this analysis, bone pain was common in cancer patients receiving chemotherapy, and was most frequently reported in the first cycle of treatment. Bone pain incidences were similar for the pegfilgrastim and filgrastim arms and slightly higher in the pegfilgrastim than in the no G-CSF arm. Bone pain may be associated with a combination of factors including disease state (eg, metastatic site), co-morbid conditions (eg, arthritis, osteoporosis), type of chemotherapy received, and growth factor use. Severe bone pain can and does occur in this population; however, this was infrequently reported in the studies included in this analysis. Disclosures: Gregory: Amgen: Consultancy. Mo:Amgen: Employment, Equity Ownership. Vogel:Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; EMD Serono: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Norvatis: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Consultancy, Honoraria; Ortho Biotech: Consultancy, Speakers Bureau. Schwartzberg:Amgen: Speakers Bureau; GSK: Speakers Bureau; BMS: Speakers Bureau.