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Randomized Controlled Trial
. 2022 Mar:8:e2100276.
doi: 10.1200/GO.21.00276.

Biosimilar Versus Originator Pegfilgrastim for Preventing Chemotherapy-Induced Neutropenia: A Phase III Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study

Ruben D Kowalyszyn  1 , Luis E Fein  2 , Martin E Richardet  3 , Mirta S Varela  4 , Eduardo Ortiz  5 , Cristian Micheri  6 , Juan J Zarba  7 , Susana Kahl  8 , Ezequiel Klimovsky  9 , Andrea A Federico  9 , Jorge H Cassini  10 , Gustavo Cortese  11 , Nestor Lago  12
Affiliations
Randomized Controlled Trial

Biosimilar Versus Originator Pegfilgrastim for Preventing Chemotherapy-Induced Neutropenia: A Phase III Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study

Ruben D Kowalyszyn et al. JCO Glob Oncol. 2022 Mar.

Abstract

Purpose: This study evaluated the efficacy, safety, and immunogenicity of biosimilar pegfilgrastim (PegFilBS) and originator pegfilgrastim (PegFilOR) in patients with stage 2-4 breast cancer.

Methods: This phase III randomized, multicenter, evaluator-blinded, noninferiority study recruited women with stage 2-4 breast cancer in Argentina who were scheduled to receive chemotherapy. Stratification was based on the breast cancer stage. The primary end point was the duration of severe neutropenia (DSN, noninferiority margin: 1 day) in the first chemotherapy cycle. Secondary end points assessed were incidence of severe neutropenia, grade 3 neutropenia, febrile neutropenia, infections, postchemotherapy hospitalization and duration, and the incidence of adverse drug reactions (ADRs).

Results: A total of 120 patients were randomly assigned to receive PegFilBS (58 patients) or PegFilOR (62 patients). Severe neutropenia occurred in 52 of 283 cycles (18.4%) for 27 patients who received PegFilBS and in 48 of 297 cycles (16.2%) for 20 patients who received PegFilOR (P = .48). During the first cycle, severe neutropenia occurred in 16 patients who received PegFilBS (DSN: 0.78 ± 1.53 days) and in 11 patients who received PegFilOR (DSN: 0.53 ± 1.25 days; 95% CI, -0.26 to 0.76 days). In the intention-to-treat analysis, the mean DSN values were 0.90 ± 1.79 days for the PegFilBS group and 0.50 ± 1.21 for the PegFilOR group (95% CI, -0.15 to 0.95 days). No significant differences were observed for the secondary efficacy end points. Three patients experienced seven ADRs in the PegFilBS group while 10 patients experienced 31 ADRs in the PegFilOR group. The most common ADR was myalgia.

Conclusion: Relative to PegFilOR, PegFilBS provided noninferior efficacy outcomes in Argentinian women with stage 2-4 breast cancer who were treated using myelosuppressive chemotherapy.

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Conflict of interest statement

Ruben D. KowalyszynConsulting or Advisory Role: BMS Argentina, MSD Oncology, Astellas Pharma, Merck SeronoSpeakers' Bureau: BMS Argentina, NovartisResearch Funding: BMS, MSD Oncology, Novartis, Roche, Astellas Pharma, Lilly, Gemabiotech, Nektar, Poliphor, AstraZeneca Luis E. FeinConsulting or Advisory Role: Novartis, Pfizer, AstraZeneca/Merck Eduardo OrtizConsulting or Advisory Role: Boehringer Ingelheim, AstraZeneca, Pfizer, Roche, Bristol Myers SquibbSpeakers' Bureau: Bristol Myers SquibbResearch Funding: Bristol Myers Squibb, Merck Sharp & Dohme, Janssen, Amgen, Astellas Pharma, Roche, Novartis/PfizerTravel, Accommodations, Expenses: Bristol Myers Squibb, Pfizer Juan J. ZarbaConsulting or Advisory Role: Pfizer/EMD Serono, Pfizer, Astellas PharmaResearch Funding: MSD Oncology, Lilly, Exelixis, Astellas PharmaExpert Testimony: LillyTravel, Accommodations, Expenses: Roche, Pfizer Ezequiel KlimovskyOther Relationship: Gema Biotech SAU, AbbVie, La Roche-Posay, Roemmers, Merz GmbH Nestor LagoEmployment: GemabiotechNo other potential conflicts of interest were reported.

Figures

FIG 1
FIG 1
CONSORT diagram of patient disposition. PegFilBS, biosimilar pegfilgrastim; PegFilOR, originator pegfilgrastim.
FIG 2
FIG 2
Primary efficacy end point duration of severe neutropenia, per-protocol, and intention-to-treat analysis.
See this image and copyright information in PMC

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