Abstract P2-11-05: Safety, immunogenicity and efficacy of proposed biosimilar pegfilgrastim (LA-EP2006) compared with reference pegfilgrastim in breast cancer: Pooled analysis of two randomized, double-blind, phase III trials
Authors: K Blackwell, P Gascon, CM Jones, A Nixon, R Nakov, M Mo, A Krendyukov, H Nadia
Journal: Cancer Research (2017)

Abstract Background: Biosimilars are highly similar to a biological reference product with no clinically meaningful differences in terms of efficacy and safety. Here we present the pooled analysis of two randomized trials (PROTECT1 and 2) comparing the efficacy, safety and immunogenicity of proposed biosimilar pegfilgrastim (LA-EP2006) with reference pegfilgrastim (Neulasta®*). Methods: Two multinational, independent, prospective, double-blind, phase III studies (EudraCT: 2011-004532-58; 2012-002039-28) enrolled adult chemotherapy-naïve women with breast cancer scheduled to receive ≤6 cycles of (neo)-adjuvant chemotherapy with docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC). Patients were randomized to receive a single 6 mg injection of LA-EP2006 or reference on Day 2 of each cycle. Primary endpoint was duration of severe neutropenia (DSN) (number of consecutive days with ANC &amp;lt;0.5x109/L) in Cycle 1. Equivalence was confirmed if the 95% confidence intervals (CI) for the difference in mean DSN between groups were within a pre-defined margin of ±1 day. Secondary efficacy endpoints included incidences of febrile neutropenia (FN), fever and infections, and depth of ANC nadir and time to ANC recovery (≥2×109/L after the nadir) in Cycle 1. Safety was assessed at each visit with follow-up visits at 4 weeks and 6 months (PROTECT1 only) after last administration of pegfilgrastim. Immunogenicity was assessed before the first pegfilgrastim injection, on Day 15 of cycle 6, and 4 weeks and 6 months (PROTECT1 only). Results: A total of 624 patients were randomized (LA-EP2006: n=314; reference: n=310). Baseline demographics were well balanced (mean age: LA-EP2006: 49.3 years, reference: 49.8; median duration (months) since initial diagnosis: LA-EP2006: 1.33 [0.1−76.0], reference: 1.35 [0.2−11.2]; ECOG status 0: LA-EP2006: 78%, reference: 75%). Mean DSN difference in Cycle 1 was -0.04 days (95% CI: -0.19, 0.11), showing statistical equivalence. FN was reported in 5.7% of patients with LA-EP2006 vs. 8.4% with reference in Cycle 1 (all cycles: 8.0% vs. 10.3%). Across all cycles, frequency of fever (LA-EP2006: 18.5%; reference: 19.7%) and infections (LA-EP2006: 15.6%; reference: 18.1%) were similar in both groups. Mean ANC time courses were almost superimposable in the two groups, with similar time and depth of ANC nadir and median time to ANC recovery was 2 days in both groups in Cycle 1. Treatment-emergent adverse events (TEAEs) were similar across groups (LA-EP2006: 92%; reference: 89%), and TEAEs with a suspected relationship to pegfilgrastim were reported in 22.6% of patients with LA-EP2006 and 21.3% with reference across all cycles, with the most frequent being musculoskeletal and connective tissue disorders (LA-EP2006: 10.2%; reference: 9.7%). Serious TEAEs were reported in 14.3% (LA-EP2006) vs. 17.1% (reference) across all cycles. No neutralizing or clinically relevant anti-pegfilgrastim antibodies were identified. Conclusions: LA-EP2006 demonstrated similar clinical efficacy and safety to reference pegfilgrastim in patients with breast cancer receiving myelotoxic chemotherapy. *Neulasta® is a registered trademark of Amgen Inc. Citation Format: Blackwell K, Gascon P, Jones CM, Nixon A, Nakov R, Mo M, Krendyukov A, Nadia H. Safety, immunogenicity and efficacy of proposed biosimilar pegfilgrastim (LA-EP2006) compared with reference pegfilgrastim in breast cancer: Pooled analysis of two randomized, double-blind, phase III trials [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-11-05.