Abstract P3-14-05: Safety of granulocyte colony-stimulating factors and their biosimilars: A meta-analysis of randomized clinical trials in breast cancer patients receiving cytotoxic chemotherapy
Authors: Krendyukov A , Botteri E , Curigliano G 
Published: February 2018

Background: Neutropenia is a common adverse event reported in cancer patients undergoing cytotoxic chemotherapy. Granulocyte colony-stimulating factors (G-CSFs) such as filgrastim and pegfilgrastim are widely used to prevent neutropenia. Several biosimilars of G-CSF are now available. Biosimilar development involves a series of comparisons between the proposed biosimilar and reference performed in a step-wise fashion to eliminate any concerns regarding the similarity of the medicines. Randomized clinical trials (RCTs) are then performed to confirm that the reference product and its biosimilar provide the same clinical efficacy and safety. Patients with breast cancer (BC) are the most sensitive population in which to confirm similarity of G-CSF biosimilars, however there are some differences between clinical studies. The aim of this meta-analysis was to compare the safety profiles of approved or proposed G-CSF biosimilars (filgrastim or pegfilgrastim) with reference G-CSF in patients with BC.

Methods: A Medline literature search up to March 2017 identified randomized clinical trials (RCTs) comparing biosimilar G-CSF to reference in BC patients. Safety analyses included calculation of risk ratios for bone pain events, myalgia events and serious adverse events. Random effect models were fitted to obtain the pooled estimates of the risk ratio for the outcomes and their corresponding 95% confidence intervals (CIs).

Results: Eight eligible RCTs were included in this meta-analysis. Risk ratios for bone pain events (risk ratio 1.01 [95% CI -0.76, 1.34]; Table), myalgia events (risk ratio 0.94 [95% CI 0.63, 1.40]) and serious adverse events (risk ratio 1.01 [95% CI 0.76, 1.34]) showed no significant differences between reference and biosimilar G-CSF.

Risk ratios for bone pain events BiosimilarsReference productsRisk RatioStudy and year of publicationReference G-CSF / Biosimilar G-CSFEventsTotalEventsTotalWeightIV, Random, 95% CIBlackwell 2015Filgrastim / Filgrastim331073810729.9%0.87 [0.59, 1.27]Blackwell 2016Pegfilgrastim / Pegfilgrastim101551715311.8%0.58 [0.27, 1.23]Harbeck 2016Pegfilgrastim / Pegfilgrastim715981577.3%0.86 [0.32, 2.33]Waller 2010Filgrastim / Filgrastim48183169521.1%1.56 [0.94, 2.59]Waller 2016Pegfilgrastim / Pegfilgrastim51127246729.7%1.12 [0.76, 1.65]Total (95% CI)731579100%1.01 [0.76, 1.34]Heterogeneity: Chi2 = 5.86, df = 4 (P = 0.21); I2 = 32% Test for overall effect: Z=0.07 (P=0.94)

Conclusions: This meta-analysis showed no differences in the safety profile of biosimilar and reference G-CSF in breast cancer patients.

Citation Format: Krendyukov A, Botteri E, Curigliano G. Safety of granulocyte colony-stimulating factors and their biosimilars: A meta-analysis of randomized clinical trials in breast cancer patients receiving cytotoxic chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-05.