Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim for the prevention of severe neutropenia, in patients with breast cancer receiving myelosuppressive chemotherapy.

Abstract

10116 Background: In 2015, filgrastim EP2006 (Zarxio) became the first biosimilar approved by the FDA for commercial use in the US. This phase III randomized, double-blind registration study in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy (TAC) compares US-licensed filgrastim, Neupogen (reference), with two groups who received alternating treatment with reference and biosimilar every other treatment cycle. Methods: A total of 218 patients receiving 5µg/kg/day filgrastim over 6 chemotherapy cycles were randomized 1:1:1:1 into 4 arms. Two arms received only 1 product, biosimilar or reference (unswitched), and 2 arms (switched) received alternating treatments every other cycle (biosimilar then reference or vice versa over cycles 1─6). Since the switch occurred from Cycle 2 onwards, this analysis compared pooled switched groups to the unswitched reference group for efficacy during Cycles 2─6. Safety was also assessed. Non-inferiority in febrile neutropenia (FN) rates between groups for Cycles 2─6 was shown if 95% confidence intervals (CIs) were within a pre-defined margin of -15%. Results: A total of107 patients switched treatment, and 51 patients received reference in all cycles. Baseline characteristics were similar between groups. Incidence of FN was 3.4% (switched) vs. 0% (reference) (95% CI: -9.65; 4.96), which is within the predefined non-inferiority margins. Infections occurred in 9.3% (switched) vs. 9.9% (reference). Hospitalization due to FN was low with 1 patient in Cycle 6 (switched). TEAEs related to filgrastim were reported in 42.1% (switched) vs. 39.2% (reference) (all cycles). Musculoskeletal/connective tissue disorders related to filgrastim occurred in 35.5% (switched) vs. 39.2% (reference) (all cycles), including bone pain (30.8% vs. 33.3%). No anti-drug antibodies were identified. Conclusions: There was no evidence of clinically meaningful differences when patients with breast cancer were switched from reference to biosimilar filgrastim, or from biosimilar to reference filgrastim. Clinical trial information: NCT01519700.