LBA2 Proposed biosimilar pegfilgrastim (LA-EP2006) compared with reference pegfilgrastim in Asian patients with breast cancer receiving myelotoxic chemotherapy: Pooled subgroup analysis of two randomized trials

Abstract

Background Two prospective, double-blind, randomized, phase III trials (PROTECT1 and 2) showed similar efficacy and safety with proposed biosimilar pegfilgrastim (LA- EP2006) and reference pegfilgrastim (NeulastaVR , Amgen Inc.) in patients with breast cancer receiving myelotoxic chemotherapy. Here we present a pooled subgroup analysis of patients of Asian ethnicity enrolled in these trials. Methods Adult chemotherapy-na¨ıve women with breast cancer scheduled to receive (neo)-adjuvant chemotherapy (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2, ::;6 cycles) were enrolled in two trials of similar design. Patients were randomized to 6 mg of LA-EP2006 or reference pegfilgrastim on Day 2 of each cycle. Primary endpoint was duration of severe neutropenia (DSN) (number of consecutive days with absolute neutrophil count [ANC] <0.5x109/L) during Cycle 1, analyzed using analysis of covariance with corresponding 95% confidence intervals (CI). Equivalence was shown if 95% CIs for the difference in mean DSN between groups were within a pre-defined margin of 6 1 day. Safety and immunogenicity were assessed during treatment with follow-up visits at 4 weeks and 6 months (PROTECT1 only) after last dose. Results A total of 174 Asian patients were randomized (LA-EP2006: n = 90; reference: n = 84). Baseline characteristics were similar in both groups. Mean DSN in Cycle 1 was 1.36 ± 0.98 days (LA-EP2006) vs. 1.35 ± 1.06 days (reference) (difference 0.01 days; 95% CI: -0.30, 0.32, indicating equivalence). There were no clinically meaningful differences between groups in secondary endpoints. Treatment-emergent adverse events (TEAEs) were similar across groups (LA-EP2006: 96.7%; reference: 97.6%) (all cycles). Serious TEAEs were reported in: LA-EP2006: 31.1%; reference: 32.1% (all cycles). No neutralizing anti-pegfilgrastim antibodies were detected. Conclusions In Asian patients with breast cancer receiving cytotoxic chemotherapy, LA-EP2006 showed similar clinical efficacy and safety compared with reference pegfilgrastim. These data were similar to the overall study population. Clinical trial identification: NCT01735175, NCT01516736 Legal entity responsible for the study Sandoz GmbH, Kundl, Austria Funding Sandoz GmbH, Kundl, Austria Disclosure N. Harbeck: Honoraria for lectures (Amgen). Honoraria for lectures/ consulting (Sandoz/Hexal). Chair of Data safety Monitoring Board. A. Krendyukov, R. Nakov: Employee of Hexal AG. M. Mo: Employee of Sandoz Inc. K.L. Blackwell: Honoraria for consulting (Sandoz, Novartis). All other authors have declared no conflicts of interest.