Clinical safety of tbo-filgrastim in chemotherapy-induced neutropenia: Integrated analysis of the phase III studies.

Abstract

e13552 Background: Tbo-filgrastim is a granulocyte colony-stimulating factor (G-CSF) approved for use in the US as a biologic under BLA 351(a) for reducing duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy (CTx) associated with a clinically significant incidence of febrile neutropenia. Here, we report an integrated analysis of clinical safety data from three Phase III studies. Methods: Safety results from three Phase III studies in breast cancer (placebo-controlled), non-small cell lung cancer, and non-Hodgkin lymphoma were integrated. All safety variables were analyzed using descriptive statistics. The incidence of treatment-emergent adverse events (TEAEs) was compared between treatment groups using Fisher's exact test (2-sided P-values). Changes in laboratory parameters from baseline were compared between the tbo-filgrastim and filgrastim treatment groups using the Wilcoxon test. Results: In the integrated analysis of CTx Cycle 1, 80.2% of 677 patients experienced a TEAE; 16.7% of these were related to study drug. The most commonly reported TEAEs were nausea, alopecia, neutropenia, diarrhea, asthenia, and vomiting, and most due to concomitant CTx. The most commonly reported drug-related TEAEs were bone pain (3.4%), diarrhea (2.2%), asthenia (2.2%), myalgia (1.9%), arthralgia (1.5%), headache (1.2%), and pyrexia (1.0%), all of which are characteristic of G-CSFs. Five patients had serious drug-related TEAEs; none caused reductions in the dose of study drug or scheduled CTx. There were 11 deaths across studies; none was considered drug related. There were no clinically significant differences between tbo-filgrastim and filgrastim in the overall incidence of deaths, serious or severe TEAEs, discontinuations due to TEAEs, or in laboratory safety variables. In all cycles of CTx, the most commonly reported TEAEs in patients treated with tbo-filgrastim correlated with those of the reference filgrastim. Conclusions: Tbo-filgrastim is safe and well tolerated in breast cancer, non-small cell lung cancer, and non-Hodgkin lymphoma patients undergoing CTx, with a safety profile similar to that of the reference filgrastim. Clinical trial information: 2004-001452-36, 2004-001450-84, 2004-001449-13.