Predictive modelling of CIN prophylaxis with biosimilar filgrastim

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Predictive modelling of CIN prophylaxis with biosimilar filgrastim

Biosimilars/Research | Posted 09/06/2017 0 Post your comment

Granulocyte colony-stimulating factors (G-CSF) stimulate white blood cell production and as such are indicated in the prophylaxis of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). Risk models of CIN/FN to date focus on predictors measured at the start of chemotherapy. Aapro and colleagues used a dynamic approach of CIN/FN risk modelling at the start of each cycle.

The MONITOR-GCSF was a pan-European, multicentre, prospective, observational study of cancer patients treated with myelosuppressive chemotherapy regimens receiving CIN/FN prophylaxis with Zarzio as per their physician’s best clinical judgement [1]. Aapro and colleagues have previously reported results from MONITOR-GCSF including incidence rates for CIN grade 4 (CIN4), FN, CIN/FN-related hospitalizations and chemotherapy disturbance (dose reduction, discontinuation, or delay) [1].

In this analysis[2], they applied predictive modelling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) at the patient- (‘ever’ during the whole period of chemotherapy) and cycle-level (during a given chemotherapy cycle). Statistical dependence of cycle data being ‘nested’ under patients was managed using Generalized Estimation Equations. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) quantified the direction and strength of the relationship between predictors and outcomes. Predictive performance of each model was evaluated.

A total of 1,447 patients were included in the MONITOR-GCSF study. Static patient-level risk models of ‘ever’ experiencing CIN/FN adverse events and consequences during a planned chemotherapy regimen included predictors related to history; risk factors; and prophylaxis initiation and intensity. The risk of an FN episode was higher in patients who were under-prophylacted versus those who were over-prophylacted. Age was associated with lower risk of an FN episode. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history; risk factors; prophylaxis initiation, intensity and duration; CIN/FN in the prior cycle; and treatment centre characteristics.

The authors concluded that their ‘real-world’ models of predictors of patients experiencing neutropenic events ‘ever’ or within a given cycle may help physicians anticipate such outcomes. A dynamic approach of reassessing the likelihood of adverse CIN/FN events at each cycle supports clinicians in assessing risk at the start of each cycle and enables personalized treatment, in line with European Organisation for Research and Treatment of Cancer (EORTC) recommendations. Prophylaxis intensity is a major determinant of CIN/FN events. ‘Over-prophylaxis’ of patients receiving chemotherapy with intermediate or low myelotoxicity levels may have benefits to patients and must be validated in future studies. Future studies should also include relative dose intensity.

References
1. Gascón P, et al. Treatment patterns and outcomes in the prophylaxis of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim (the MONITOR-GCSF study). Support Care Cancer. 2016;24(2):911-25.
2. Aapro M, et al. Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study). Ann Oncol. 2016;27(11):2039-45.

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