Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer
A partir de données de deux essais de phase III incluant un total de 624 patientes atteintes d'un cancer du sein, cette étude évalue l'efficacité, du point de vue de la durée moyenne d'une neutropénie sévère pendant le premier cycle de chimiothérapie, d'un composé appelé LA-EP2006, un médicament biosimilaire au pegfilgrastim, pour prévenir une neutropénie induite par une chimiothérapie adjuvante ou néo-adjuvante à base de docétaxel, doxorubicine et cyclophosphamide
Background: Following the functional and physicochemical characterization of a proposed biosimilar, comparative clinical studies help to confirm biosimilarity by demonstrating similar safety and efficacy to the reference product in a sensitive patient population. Patients and methods: LA-EP2006 is a proposed biosimilar that has been developed for pegfilgrastim, a long-acting form of granulocyte colony stimulating factor (G-CSF) for the prevention of neutropenia. The current analysis reports data pooled from two independent, multinational, prospective, randomized, controlled, double-blind phase III studies of similar design comparing the safety and efficacy of reference pegfilgrastim with LA-EP2006 in patients with breast cancer receiving myelotoxic (neo)-adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy and requiring G-CSF. Results: A total of 624 patients were randomized in the PROTECT-1 and PROTECT-2 studies (NCT01735175; NCT01516736) (LA-EP2006: n = 314; reference: n = 310). Baseline characteristics of patients were well balanced across treatment groups. The primary endpoint, mean duration of severe neutropenia in the first chemotherapy cycle was similar in both the LA-EP2006 and reference groups (1.05 ± 1.055 days vs 1.01 ± 0.958 days), with a treatment difference of –0.04 days (95% CI: –0.19–0.11) that met the equivalence criteria (the 95% CI were within the defined margin of ± 1 day). Secondary endpoints, such as the nadir of absolute neutrophil count and the incidence of febrile neutropenia, were also similar between LA-EP2006 and reference pegfilgrastim. The safety and tolerability profile of LA-EP2006 was similar to that observed with reference pegfilgrastim, and there were no reports of neutralizing antibodies. Conclusions: This pooled analysis confirms, as a part of totality of evidence approach, that the proposed biosimilar pegfilgrastim LA-EP2006 has a comparable efficacy and safety profile to reference pegfilgrastim in patients with breast cancer receiving TAC chemotherapy.