Extrapolation in Practice: Lessons from 10 Years with Biosimilar Filgrastim

AbstractBiosimilar filgrastim (Sandoz) was approved in Europe in 2009 and, in 2015, was the first biosimilar approved in the USA. These authorizations were based on the “totality of evidence” concept, an approach that considers data from structural and functional characterization and comparability analysis and non-clinical and clinical studies. For biosimilar filgrastim, phase III confirmatory clinical studies were performed in the most sensitive population, pa tients with breast cancer undergoing myelosuppressive chemotherapy. In Europe and the USA, approval was granted for all indications of the reference biologic. Hence, stem cell mobilization and severe chronic neutropenia indications were approved on the basis of extrapolation, with no clinical data a vailable at the time of market authorization in the EU. Although extrapolation is well-accepted in biologic development and regulatory contexts, it remains a misunderstood part of the biosimilarity concept in the medical community. Since approval, more than a decade of obtained clinical experience s upports the totality of evidence and reassures clinicians regarding the efficacy and safety of biosimilar filgrastim. This includes real-world data from MONITOR-GCSF, a multicenter, prospective, observational study describing treatment patterns and clinical outcomes of patients with cancer (n = 1447) receiving biosimilar filgrastim for the prophylaxis of chemotherapy-induced neutropenia in solid tumors ...
Source: BioDrugs - Category: Drugs & Pharmacology Source Type: research

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Abstract Triple negative breast cancer (TNBC) is a highly heterogeneous disease, which influences the therapeutic response and makes difficult the discovery of effective targets. This heterogeneity is attributed to the presence of breast cancer stem cells (BCSCs), which determines resistance to chemotherapy and subsequently disease recurrence and metastasis. In this context, this work aimed to evaluate the morphological and phenotypic cellular heterogeneity of two TNBC cell lines cultured in monolayer and tumorsphere (TS) models by fluorescence and electron microscopy and flow cytometry. The BT-549 and Hs 578T ana...
Source: European Biophysics Journal : EBJ - Category: Physics Authors: Tags: Eur Biophys J Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Journal of Functional Foods - Category: Nutrition Source Type: research
Authors: Giuli MV, Giuliani E, Screpanti I, Bellavia D, Checquolo S Abstract Triple-negative breast cancer (TNBC) is a subgroup of 15%-20% of diagnosed breast cancer patients. It is generally considered to be the most difficult breast cancer subtype to deal with, due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), which usually direct targeted therapies. In this scenario, the current treatments of TNBC-affected patients rely on tumor excision and conventional chemotherapy. As a result, the prognosis is overall poor. Thus, the identification and...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Mindaugas Valius Antitumor drug resistance remains a major challenge in cancer chemotherapy. Here we investigated the mechanism of acquired resistance to a novel anticancer agent RH1 designed to be activated in cancer cells by the NQO1 enzyme. Data show that in some cancer cells RH1 may act in an NQO1-independent way. Differential proteomic analysis of breast cancer cells with acquired resistance to RH1 revealed changes in cell energy, amino acid metabolism and G2/M cell cycle transition regulation. Analysis of phosphoproteomics and protein kinase activity by multiplexed kinase inhibitor beads showed an increase in ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
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Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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