Dataset Information

Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study).

ABSTRACT:

Background

Risk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle.

Design

We applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses 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. Predictive performance of each model was evaluated using bootstrapped c concordance statistics.

Results

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. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history, risk factors, and prophylaxis initiation and intensity; as well as prophylaxis duration, CIN/FN in prior cycle, and treatment center characteristics.

Conclusions

These 'real-world evidence' models provide clinicians with the ability to anticipate CIN/FN adverse events and their consequences at the start of a chemotherapy line (static models); and, innovatively, to assess risk of CIN/FN adverse events and their consequences at the start of each cycle (dynamic models). This enables individualized patient treatment and is consistent with the EORTC recommendation to re-appraise CIN/FN risk at the start of each cycle. Prophylaxis intensity (under-, correctly-, or over-prophylacted relative to current EORTC guidelines) is a major determinant. Under-prophylaxis is clinically unsafe. Over-prophylaxis of patients administered chemotherapy with intermediate or low myelotoxicity levels may be beneficial, both in patients with and without risk factors, and must be validated in future studies.

SUBMITTER: Aapro M

PROVIDER: S-EPMC5091320 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study).

Aapro M M Ludwig H H Bokemeyer C C Gascón P P Boccadoro M M Denhaerynck K K Krendyukov A A Gorray M M MacDonald K K Abraham I I

Annals of oncology : official journal of the European Society for Medical Oncology 20161101 11

<h4>Background</h4>Risk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle.<h4>Design</h4>We applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses at t ...[more]

PMID: 27793849

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Project description:Background:The granulocyte-colony stimulating factor (G-CSF) biosimilar filgrastim (Nivestim™) reduces the duration and severity of neutropenia and the frequency of occurrence of febrile neutropenia (FN). Administration of this biosimilar filgrastim and the patient population receiving it at home have not been sufficiently documented in day-to-day medical practice. Insight into home administration may help optimize the management of FN in this setting, potentially at a reduced cost and patient burden vs hospital administration. Materials and methods:This was a prospective, non-interventional, non-comparative, multisite study involving 171 patients across 29 sites treated with at least one dose of filgrastim. Mean age was 59.3 years, and most patients were female and G-CSF-naïve. The data collected originated from paper-based patient questionnaires and routine documentation by the treating physicians. The primary endpoint was the characterization of patients treated with filgrastim. Secondary endpoints were satisfaction with filgrastim, effectiveness, safety and tolerability, and compliance with prescription. Results:Most patients had solid tumors (95.9%), mainly located in the breast, while 4.7% had malignant hematological disease. Solid tumors were recorded as grade 1 (7.9%), grade 2 (28.0%), grade 3 (45.7%), and grade 4 (3.0%), and the majority of patients classified at TNM Stages I and II. Many patients (71.0%) could self-inject filgrastim and 72.2% found the handling instructions "extremely straightforward and easy to understand" at least once. Nearly all (99.4%) patients found the syringes "easy to use" at least once and 91.7% were willing to continue home administration. The mean patient satisfaction score for home administration was 1.9±0.9, ranging from 1 (very satisfied) to 6 (absolutely dissatisfied). No cases of neutropenia were observed and only one event of FN occurred. Conclusion:Home-based prophylaxis for FN with filgrastim was found to be effective, well tolerated, and well received by patients (ClinicalTrials.gov Identifier: NCT02956967).

Project description:Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen®. Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice.The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world' clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy.Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 patients. Last patient, last visit for each study will be December 2013 and March 2014 respectively.The NEXT and VENICE studies will provide long-term safety, efficacy and practice pattern data in patients receiving Nivestim™ to support myelosuppressive chemotherapy in real world clinical practice. These data will improve our understanding of the performance of Nivestim™ in patients encountered in the general patient population.NEXT NCT01574235, VENICE NCT01627990.

Project description:BackgroundThe ZOHé study was a prospective, non-interventional, multicentre study in France to assess the use of biosimilar filgrastim Zarzio® (Sandoz filgrastim) in routine clinical practice in patients at risk of neutropenia-inducing chemotherapy (CT).MethodsPatients ??18 years undergoing CT for a malignant disease and with a first prescription for Zarzio® were enrolled in two cohorts according to tumour type: solid tumour or haematological malignancy; results from the solid tumour cohort are reported here. Analyses primarily described the prescription and use of Zarzio® in current practice, and also included identification of factors linked to prescription for primary prophylaxis and comparison of Zarzio® use in relation to European Organisation for Research and Treatment of Cancer (EORTC) guidelines.ResultsResponses were obtained from 125 physicians and 1179 patients with solid tumours, allowing robust statistical analysis of the data. Use of Zarzio® in clinical practice was relatively standardised and followed label indication. The patient profile was in line with EORTC guidelines for granulocyte colony-stimulating factor (G-CSF) febrile neutropenia (FN) prophylaxis, and the majority of patients had ??1 EORTC factor(s) for increased risk of febrile neutropenia. Some patients (10.8%) received Zarzio® despite receiving CT regimens categorised in guidelines as low (<?10%) FN risk ('over prophylaxis'). Nearly half of patients' CT regimens did not have a recommended FN risk category. Zarzio® was commonly initiated as primary prophylaxis; initiation in Cycle ??2 of the current line of CT was associated more with a history of neutropenia. The safety profile of Zarzio® was confirmed.ConclusionsUse of Zarzio® in routine clinical practice is generally in line with EORTC guidelines for prophylaxis of CT-induced neutropenia. Patient-related risk factors appear to be a stronger driver of clinicians' decision to initiate Zarzio® than CT risk category for FN. The intrinsic risk of FN associated with a specific CT protocol is often miscategorised by physicians. In contrast to earlier reports of underuse of G-CSF prophylaxis, over prophylaxis is observed in a small subgroup of patients with FN risk of <?10%.

Project description:PURPOSE:Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile neutropenia (FN) prophylaxis remains unknown. A systematic review was therefore performed. METHODS:Embase, Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, and conference proceedings were searched from 1946 to April 2016 for trials that reported the effectiveness of primary FN prophylaxis with FEC-D chemotherapy. Outcome measures were incidence of FN; treatment-related hospitalizations; chemotherapy dose delays, reductions, and discontinuations; and adverse events from prophylaxis. RESULTS:Of 2,205 identified citations, eight studies (n = 1,250) met our eligibility criteria. Three additional studies (n = 293) were identified from a prior systematic review. Three randomized controlled trials (n = 576), one phase IV single-arm trial (n = 69), one prospective observational study (n = 37), and six retrospective studies (n = 861) were identified. Agents investigated were pegfilgrastim (n = 108), filgrastim (n = 1,119), and ciprofloxacin (n = 89). The heterogeneity of studies meant that a narrative synthesis of results was performed. Median FN rates for patients who received FEC-D with and without primary prophylaxis were 10.1% (interquartile range [IQR], 3.9% to 22.6%) and 23.9% (IQR, 9.2% to 27.3%), respectively. In the absence of primary prophylaxis, FN was more common during docetaxel than during FEC. Data from six studies showed a median rate of dose reductions and delays of 6.1% (IQR, 3.1% to 14.3%) and 19.3% (IQR, 10.5% to 32.8%), respectively, that occurred as a consequence of FN. Toxicity from prophylaxis itself was rarely reported. CONCLUSION:Primary FN prophylaxis is effective in patients who receive FEC-D chemotherapy. The paucity of prospective data makes optimal recommendations about the choice and timing of prophylaxis challenging.

Dataset Information

Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study).

Background

Design

Results

Conclusions

Publications

Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study).

Similar Datasets

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