Matthew Turner

Treatment patterns and outcomes in the management of anaemia in cancer patients in Europe: findings from the Anaemia Cancer Treatment (ACT) study.

OBJECTIVES To examine anaemia management in cancer patients treated with erythropoiesis-stimulating agents (ESAs) in Europe. METHODS Retrospective pharmacoepidemiologic study of 2192 patients from 307 centres. Minimum of 3 visits over 8-10 weeks with ESA treatment initiated at visit 1. RESULTS Most patients were treated per guidelines, except for low iron supplementation rates. Mean Hb rose from 9.54+/-0.95 g/dl to 10.88+/-1.49 g/dl at visit 3, without concomitant rise in WHO/ECOG score. Response rates were 65.0% (Hb increase (upward arrow) > or = 1 g/dl); 54.3% (Hb increase (upward arrow) > or = 1 g/dl in 8 weeks); 38.9% (haematopoietic response); 33.7% (Hb increase (upward arrow) > or = 2 g/dl) and 18.8% (Hb between 12.0 and 12.9 g/dl) CONCLUSIONS Treatment patterns were guideline congruent, except for (intravenous) iron supplementation. Hb increased by 1.34 g/dl. A net erythropoiesis boost of Hb > or =1 g/dl is attainable in two-thirds of patients and should be condensed to 8 weeks on an individual patient basis. Anaemia management in Europe has improved significantly. The general effectiveness and relative safety of judicious ESA treatment are evident.

Background and methodology of MONITOR-GCSF, a pharmaco-epidemiological study of the multi-level determinants, predictors, and clinical outcomes of febrile neutropenia prophylaxis with biosimilar granulocyte-colony stimulating factor filgrastim

The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of Zarzio(®) in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates statistical methodologies from the social and behavioral sciences; assesses factors predictive of poor treatment response; and evaluates the congruence of treatment with EORTC guidelines and the approved label. This pan-European study will recruit at least 1000 patients from a minimum of 75 centers and follow them for maximum 6 cycles of chemotherapy. Apart from descriptive and associative procedures, statistical analysis will include variance attribution methods; hierarchical linear, logistic, and Poisson modeling; Kaplan-Meier time-to-event analysis, Mantel-Cox log-rank or generalized Wilcoxon-Breslow tests, and Cox proportional hazards modeling; and clustering and related data mining techniques.

Managing cancer-related anaemia in congruence with the EORTC guidelines is an independent predictor of haemoglobin outcome: initial evidence from the RESPOND study.

PURPOSE To model the relationship between scores for practicing in congruence (CSs; 0-10) with EORTC guidelines for erythropoietic proteins (EPs) and haemoglobin (Hb) outcomes observed in the validation study of the RESPOND system. METHODS Thirty four patient pairs matched on cancer type and chemotherapy in pre- (retrospective; clinicians not using RESPOND) and post-cohorts (prospective; clinicians using RESPOND) followed over 4 months following EP treatment initiation. CSs quantify the extent that care was guideline-adherent. Linear and logistic regressions controlling for cohort examined Hb outcomes as a function of CSs. RESULTS A one-point increase in CS was associated with 0.60g/dL increase in Hb at month 4 (R(2)=0.40) and 0.56g/dL increase in Hb change from month 1-4 (R(2)=0.33). Each one-point increase in CS increased the odds of reaching Hb>or=11g/dL by 3.14 (R(2)=0.42) and Hb>or=12g/dL by 2.77 (R(2)=0.45). CONCLUSION Guideline-adherent EP treatment may improve Hb outcomes but specifically designed outcomes studies are necessary.

Update on the MONITOR-GCSF study of biosimilar filgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia in cancer patients: Protocol amendments

The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of biosimilar filgrastim in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. The background and methodology of this study are described in an article published concurrently in this journal. As important amendments have been made to the protocol, and the purpose of the prior article was to serve as a resource for future referencing, we detail these amendments in this present article: explicit statement about the use of biosimilar filgrastim for both primary and secondary prophylaxis of chemotherapy-induced febrile neutropenia in the objectives and methodology of the study; length of observation; the addition of stage III and stage IV ovarian cancer and multiple myeloma to the tumor types studied; and the deletion of dose dense chemotherapy regimens as an exclusion criterion.

Modeling of treatment response to erythropoiesis-stimulating agents as a function of center- and patient-related variables: results from the Anemia Cancer Treatment (ACT) study

BACKGROUND In anemic cancer patients treated with erythropoiesis-stimulating agent (ESA), (i) to examine the proportion of variance in hemoglobin (Hb) outcomes attributable to patients versus center, country, and region and (ii) to develop predictive models of treatment response. METHODS Retrospective study with a minimum of three visits at 1-month intervals. Three hundred and seven centers in 13 European countries contributed 2192 anemic ESA-treated cancer patients. Treatment response criteria included: Hb increase > or =1 g/dl, Hb increase > or =1 g/dl within 8 weeks, hematopoietic response (Hb increase > or =2 g/dl or Hb > or = 12 g/dl), Hb increase > or =2 g/dl, and Hb between 12 and 13 g/dl. RESULTS Hb increased from 9.54 +/- 0.95 g/dl (baseline) to 10.88 +/- 1.49 g/dl (visit 3). Hb change from visits 1 to 2 (index of relative immediacy of response to ESA) averaged 0.81 +/- 1.17 g/dl. The proportion of variance in Hb outcomes attributable to center was 11.8%-34.3%, country 2.9%-20.7%, and region 0.0%-7.6%. Immediacy of response to ESA was the most prevalent predictor of treatment response, followed by diagnosis of hematological malignancy and age <70 years. CONCLUSIONS . Hb outcomes are determined significantly by the treating center and less so by country or region. The remaining majority variance was attributable to patient-related factors. Immediacy of response to ESA is the single most important predictor of treatment. When used according to guidelines, ESAs are effective in managing anemia in cancer patients and improving treatment outcomes.

Prevention and Treatment of Chemotherapy-Induced Neutropenia with the Biosimilar Filgrastim: A Non-Interventional Observational Study of Clinical Practice Patterns

Background: Biosimilars are similar but non-identical versions of existing biological drugs. The HEXAFIL study was an observational study that assessed the clinical usage, safety and efficacy of the biosimilar filgrastim in routine clinical practice in Germany. Patients and Methods: A total of 1,337 cancer patients received the biosimilar filgrastim for primary prophylaxis (PP), secondary prophylaxis (SP) or interventional treatment (TX) plus chemotherapy. Data including neutropenic complications and adverse events (AEs) were documented for up to 3 consecutive cycles. Results: In cycle 1, 44.9% of the patients received the biosimilar filgrastim as PP, 31.0% as SP, and 23.6% as TX. Approximately 90% of the patients required no modifications to their chemotherapy regimen, with lower rates among the PP/SP versus the TX patients. Neutropenic complications occurred in 7.9%, 6.9%, and 3.9% of the patients (cycles 1, 2, and 3, respectively). Only 1.8% of the patients experienced febrile neutropenia during cycle 1. Earlier and longer filgrastim treatment reduced grade 3/4 leukopenia and neutropenic complications. The observed safety/tolerability profile was as expected; the most common AE (4.3%) was musculoskeletal back/bone pain. Conclusion: In this observational real-life study of clinical practice, the biosimilar filgrastim was effective and well tolerated, with results consistent with those reported in phase II and phase III trials.

Intraclass correlation metrics for the accuracy of algorithmic definitions in a computerized decision support system for supportive cancer care

As part of the development of a computerized clinical decision support system for anemia management in cancer patients, we applied psychometric principles and techniques to assess the accuracy of the algorithmic operationalizations of a set of evidence-based practice guidelines. In an iterative rating process, five medical and nursing experts rated 27 algorithmic sets derived from 18 guidelines, the objective being an intraclass coefficient (ICC) exceeding 0.90. The first round of review yielded an ICC of 1.00 for 22 sets. After revision and resubmission to the expert panel, an ICC of 1.00 was obtained for the additional five sets. The evolving decision support system is based on algorithms that accurately specify evidence-based guidelines for anemia management in cancer patients.

Abstract P5-15-19: Prophylaxis of chemotherapy-induced febrile neutropenia with biosimilar filgrastim: Description of patients, treatment patterns and outcomes in the MONITOR-GCSF study in the breast cancer cohort

Introduction: MONITOR-GCSF is a European prospective observational study of practice patterns and outcomes of patients treated with Sandoz9 filgrastim (EP-2006) in the prophylaxis of chemotherapy-induced febrile neutropenia (CIN/FN). Objectives: To describe patients, treatment patterns of EP-2006, and outcomes in the breast cancer cohort of the MONITOR-GCSF study. Methods: Prospective observational study following 466 evaluable patients from 23 centers in Europe for up to 6 cycles within a single chemotherapy line including a total of 2714 cycles. Results: Median age was 56y (range 25-91); all but 3 patients were female. Table 1 presents chemotoxicity in terms of % FN risk and prophylaxis type. GCSF was correctly initiated as either primary or secondary prophylaxis per EORTC guideline recommendations (considering chemotherapy-related FN risk and patient-related factors) in 62% of patients. Eleven percent were undertreated, i.e., secondary prophylaxis when primary was indicated–either when CIN/FN risk >20% or when CIN/FN risk was 10-20% in combination with patient-related risk factors. Twenty-seven percent were overtreated, i.e., primary or secondary when not indicated–either primary prophylaxis in Conclusions: Variation in treatment with biosimilar GCSF in breast cancer patients is evident in terms of decision to treat with primary prophylaxis relative to guideline recommendations as well as day of initiation, duration and dose, yet incidence of CIN/FN and related events is low. Forthcoming analyses will determine whether variability in treatment is associated with differential outcomes. Citation Format: Pere Gascon, Matti Aapro, Heinz Ludwig, Mario Boccadoro, Carsten Bokemeyer, Matthew Turner, Michael Muenzberg, Ivo Abraham, Kris Denhaerynck, Karen MacDonald. Prophylaxis of chemotherapy-induced febrile neutropenia with biosimilar filgrastim: Description of patients, treatment patterns and outcomes in the MONITOR-GCSF study in the breast cancer cohort [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-19.