Edoardo Botteri1, Andriy Krendyukov2, Giuseppe Curigliano3. 1. Women and Children's Division, Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, Oslo, Norway; Department of Bowel Cancer Screening, Cancer Registry of Norway, Oslo, Norway. 2. Hexal AG, Holzkirchen, Germany. 3. European Institute of Oncology, Division of New Drug Development, Italy; Department of Oncology and Hematology, University of Milano, Milano, Italy. Electronic address: Giuseppe.curigliano@ieo.it.
Abstract
BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs) are widely used to prevent neutropenia in cancer patients undergoing myelosuppressive chemotherapy. Several biosimilar medicines of G-CSF are now available, with their development involving a step-wise series of comparisons to demonstrate similarity to reference biologics. Randomised clinical trials (RCTs) are considered confirmatory, and for G-CSF biosimilars, patients with breast cancer (BC) undergoing myelosuppressive chemotherapy are the most sensitive population in which to confirm similarity. This meta-analysis aimed to compare the clinical efficacy and safety 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 RCTs comparing biosimilar G-CSF to reference in BC patients. The primary efficacy end-point was mean difference in duration of severe neutropenia (DSN). Secondary efficacy end-points were differences in depth of absolute neutrophil count (ANC) nadir, time to ANC recovery and incidence of febrile neutropenia. 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 mean difference for continuous outcomes and the risk ratio for dichotomous outcomes and their corresponding 95% confidence intervals (CIs). FINDINGS: Eight eligible RCTs were included in this meta-analysis. Overall difference in DSN between reference and biosimilar medicines was not statistically significant (0·06 d [95% CI -0·05, 0·17]). The analysis of secondary efficacy end-points showed no significant differences between reference biologics and biosimilar medicines, as well as the analysis of bone pain events, myalgia events and serious adverse events. INTERPRETATION: This meta-analysis showed no significant differences in clinical efficacy and safety between biosimilar and reference G-CSF in BC patients.
BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs) are widely used to prevent neutropenia in cancerpatients undergoing myelosuppressive chemotherapy. Several biosimilar medicines of G-CSF are now available, with their development involving a step-wise series of comparisons to demonstrate similarity to reference biologics. Randomised clinical trials (RCTs) are considered confirmatory, and for G-CSF biosimilars, patients with breast cancer (BC) undergoing myelosuppressive chemotherapy are the most sensitive population in which to confirm similarity. This meta-analysis aimed to compare the clinical efficacy and safety 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 RCTs comparing biosimilar G-CSF to reference in BC patients. The primary efficacy end-point was mean difference in duration of severe neutropenia (DSN). Secondary efficacy end-points were differences in depth of absolute neutrophil count (ANC) nadir, time to ANC recovery and incidence of febrile neutropenia. 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 mean difference for continuous outcomes and the risk ratio for dichotomous outcomes and their corresponding 95% confidence intervals (CIs). FINDINGS: Eight eligible RCTs were included in this meta-analysis. Overall difference in DSN between reference and biosimilar medicines was not statistically significant (0·06 d [95% CI -0·05, 0·17]). The analysis of secondary efficacy end-points showed no significant differences between reference biologics and biosimilar medicines, as well as the analysis of bone pain events, myalgia events and serious adverse events. INTERPRETATION: This meta-analysis showed no significant differences in clinical efficacy and safety between biosimilar and reference G-CSF in BC patients.
Authors: Ka-Won Kang; Byung-Hyun Lee; Min Ji Jeon; Eun Sang Yu; Dae Sik Kim; Se Ryeon Lee; Hwa Jung Sung; Chul Won Choi; Yong Park; Byung Soo Kim Journal: Cancer Med Date: 2020-07-07 Impact factor: 4.452