Multi-level Evaluation of Chemotherapy-induced Febrile Neutropenia Prophylaxis, Outcomes, and Determinants With Granulocyte-colony Stimulating Factor (Monitor-GCSF)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sandoz
ClinicalTrials.gov Identifier:
NCT01459653
First received: August 30, 2011
Last updated: July 7, 2015
Last verified: July 2015
  Purpose

This international, prospective, observational, open-label, pharmaco-epidemiologic study observes cancer patients at risk for chemotherapy-induced febrile neutropenia (FN) who are receiving filgrastim biosimilar (EP2006) for primary or secondary FN prophylaxis to better describe the patient population at risk for FN and treated prophylactically in physician's best clinical judgement with filgrastim biosimilar (EP2006), to describe prophylaxis patterns involving filgrastim biosimilar (EP2006), and to evaluate hematology levels and variability in hematological outcomes, impact on chemotherapy delivery, radiotherapy, surgery, and mortality. Additionally the study aims to identify patient cohorts who are vulnerable to poor response to FN prophylaxis and experience break-through episodes of FN, understand the differences between prophylaxis responders and non-responders, and describe the degree to which prophylaxis of FN is in congruence with guideline recommendations.


Condition
Febrile Neutropenia
Cancer
Breast Cancer
Ovarian Cancer
Lung Cancer
Prostate Cancer
Multiple Myeloma
Bladder Cancer
B-cell Lymphoma

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: International, Prospective, Open-label, Multicenter, Pharmacoepidemiological Study to Determine Predictors of Clinical Outcomes in Chemotherapy-treated Cancer Patients at Risk for Febrile Neutropenia and Treated Prophylactically With Filgrastim Biosimilar.

Resource links provided by NLM:


Further study details as provided by Sandoz:

Primary Outcome Measures:
  • Chemotherapy Toxicity (%FN Risk) [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 1: To describe the cancer patients requiring chemotherapy who, in their treating physician's best clinical judgment, are receiving EP2006 for the primary or secondary prophylaxis of FN in terms of demographics, clinical status, medical history, concomitant comorbid conditions and current status of disease, and prior and concomitant medications.

    Chemotherapy regimens were classified for FN risk (<10% risk, 10-20% risk or >20% risk) according to the published rates in the EORTC Guidelines under consideration of agent(s) and schedules.

    ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia;


  • Cancer Treatment Type - Ever Received During Study [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 1: To describe the cancer patients requiring chemotherapy who, in their treating physician's best clinical judgment, are receiving EP2006 for the primary or secondary prophylaxis of FN in terms of demographics, clinical status, medical history, concomitant comorbid conditions and current status of disease, and prior and concomitant medications.

    ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia;


  • Fever and Infections Ever During the Study [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]

    Objective 1: To describe the cancer patients requiring chemotherapy who, in their treating physician's best clinical judgment, are receiving EP2006 for the primary or secondary prophylaxis of FN in terms of demographics, clinical status, medical history, concomitant comorbid conditions and current status of disease, and prior and concomitant medications.

    ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia;


  • Clinical Events Ever During Study (Frequency Threshold: 5%) [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]

    Objective 1: To describe the cancer patients requiring chemotherapy who, in their treating physician's best clinical judgment, are receiving EP2006 for the primary or secondary prophylaxis of FN in terms of demographics, clinical status, medical history, concomitant comorbid conditions and current status of disease, and prior and concomitant medications.

    ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia


  • Type of EP2006 Prophylaxis [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • Type of EP2006 Prophylaxis by Gender [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • Type of EP 2006 Prophylaxis by Age Group [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • Type of EP 2006 Prophylaxis by Tumor Type [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • Concomitant Antibiotic Prophylaxis [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose (All Cycles) [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose (Enrollment Cycle) [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose (Cycle 1) [ Time Frame: Cycle 1. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose (Cycle 2) [ Time Frame: Cycle 2. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose (Cycle 3) [ Time Frame: Cycle 3. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose (Cycle 4) [ Time Frame: Cycle 4. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose (Cycle 5) [ Time Frame: Cycle 5. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose (Cycle 6) [ Time Frame: Cycle 6. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose by Patient Weight: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose by Tumor Type: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • Patient Weight by Tumor Type (Solid Tumor vs. Hematological Tumor) [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Dose by Chemotherapy Toxicity: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation: All Cycles [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation: Cycle 1 [ Time Frame: Cycle 1. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation: Cycle 2 [ Time Frame: Cycle 2. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation: Cycle 3 [ Time Frame: Cycle 3. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation: Cycle 4 [ Time Frame: Cycle 4. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation: Cycle 5 [ Time Frame: Cycle 5. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation: Cycle 6 [ Time Frame: Cycle 6. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation by Tumor Type (Solid Tumor vs. Hematological Tumor): Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation by Prophylaxis Type: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Day of Initiation by Chemotherapy Toxicity: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Treatment Duration in Any Cycle [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Treatment Duration in Cycle 1 [ Time Frame: Cycle 1. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Treatment Duration in Cycle 2 [ Time Frame: Cycle 2. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Treatment Duration in Cycle 3 [ Time Frame: Cycle 3. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Treatment Duration in Cycle 4 [ Time Frame: Cycle 4. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Treatment Duration in Cycle 5 [ Time Frame: Cycle 5. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Treatment Duration in Cycle 6 [ Time Frame: Cycle 6. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Duration by Tumor Type: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Duration by Prophylaxis Type: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • EP2006 Duration by Chemotherapy Toxicity: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

  • Percentage of Patients With Each EORTC-identified Risk Factors for FN at Baseline [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    * Advanced disease is defined as Stage IV (Stage III or IV if multiple myeloma) AND prior chemotherapy in metastatic setting. The PRS is a quantification of eight individual patient risk factors (EORTC guidelines-2010).

    CV: cardiovascular; EORTC: European Organization for Research and Treatment in Cancer; FN: febrile neutropenia; Hb: hemoglobin


  • Percentage of Patients With Each EORTC-identified Risk Factors for FN in Patients With Chemotherapy Risk 10-20% at Baseline [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    * Advanced disease is defined as Stage IV (Stage III or IV if multiple myeloma) AND prior chemotherapy in metastatic setting CV: cardiovascular; EORTC: European Organization for Research and Treatment in Cancer; FN: febrile neutropenia; Hb: hemoglobin


  • Patient Risk Score (PRS) for All Patients [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    Patient risk score (PRS) shows the individual patient risk for FN.The PRS is a sum of eight weighted individual patient risk factors for FN and results in a possible score of 0 to 11 (highest risk for FN). The risk factors were assigned weights based on the level of risk specified by guidelines and SC consensus (age > 65 years: 3.0; advanced disease: 1.5; history of FN: 3.0; No antibiotic prophylaxis: 0.5; poor performance/nutritional status: 1.5; female gender: 0.5; Hb<12g/dL: 0.5; Renal, CV or liver disease: 0.5).

    Advanced disease: Stage IV or Stage III + prior chemotherapy in metastatic setting; CV: cardiovascular; EORTC: European Organization for Research and Treatment in Cancer; FN: febrile neutropenia


  • Patient Risk Score (PRS) for Patients Receiving Chemotherapy With 10-20% FN Risk by Tumor Type [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    Patient risk score (PRS) shows the individual patient risk for FN.The PRS is a sum of eight weighted individual patient risk factors for FN and results in a possible score of 0 to 11 (highest risk for FN). The risk factors were assigned weights based on the level of risk specified by guidelines and SC consensus (age > 65 years: 3.0; advanced disease: 1.5; history of FN: 3.0; No antibiotic prophylaxis: 0.5; poor performance/nutritional status: 1.5; female gender: 0.5; Hb<12g/dL: 0.5; Renal, CV or liver disease: 0.5).

    Advanced disease: Stage IV or Stage III + prior chemotherapy in metastatic setting; CV: cardiovascular; EORTC: European Organization for Research and Treatment in Cancer; FN: febrile neutropenia


  • Percentage of Patients With Each Prophylaxis Decision by Chemotherapy-associated FN Risk [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    FN: Febrile Neutropenia; EORTC: European Organisation for Research and Treatment of Cancer


  • Percentage of Patients With Each Chemotherapy Risk Score (CRS) Result by Tumor Type [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    The CRS quantifies whether the decision to initiate EP2006 as either primary or secondary prophylaxis is consistent with the EORTC guideline (2010) recommendation based upon the patient's chemotherapy toxicity (<10%, 10-20% or >20% risk of FN) and the PRS. There are three possible results: under-treated, correctly treated, over-treated


  • EP2006 Day of Initiation Relative to Guidelines by Cancer Type [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    ^ 168 cycles in which ZARZIO® was initiated on day 4 or later involved regimens deemed by the Study Steering Committee to be suitable for GCSF initiation any day after chemotherapy (day 1 or later), e.g., etoposide; hence, these patients were re-classified as being within guidelines

    DLBCL- Diffuse Large B-Cell Lymphoma. Guidelines refers to EORTC 2010 guidelines


  • GCSF Initiation Score (GIS) [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    ANC=Absolute Neutrophil Count; GIS Score 0 (EP2006 initiated on day 0 of chemotherapy or on day 10 or later); GIS Score 0.50 (EP2006 initiated on days 7-9 of chemotherapy); GIS Score 0.75 (EP2006 initiated on days 4-6 of chemotherapy); GIS Score 1.00 (EP2006 initiated per EORTC guidelines (2010) on days 1-3 after chemotherapy)

    ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; EORTC=European Organization for Research and Treatment in Cancer; FN=Febrile Neutropenia; GCSF=Granulocyte Colony-Stimulating Factor; GIS=Granulocyte Colony-Stimulating Factor Initiation Score


  • GCSF Persistence Score (GPS) [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    The GPS grades persistence based on the number of cycles in the line of chemotherapy in which EP2006 was administered, D, relative to the number of cycles in which it should have been continued, C. Thus, the GPS = D/C and ranges from 0 to 1.0

    ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; EORTC=European Organization for Research and Treatment in Cancer; FN=Febrile Neutropenia; GCSF=Granulocyte Colony-Stimulating Factor


  • GCSF Congruence Score (GCS) [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 3: To determine the extent to which the primary and secondary prophylaxis of FN in cancer patients is in congruence with the EORTC best practice guidelines and dosing recommendations, and whether this is associated with better outcomes.

    The GCS is computed at the patient level as an overall grade of how congruent actual GCSF treatment is to recommended treatment. The GCS is computed as follows and scores range from 0 to 3: GCS = Σ(CRS + mean GIS over all cycles + GPS), with higher scores indicating higher congruence.

    CRS: Chemotherapy Risk Score (0 or 1 with 1 best); FN: febrile neutropenia; GCSF: granulocyte colony-stimulating factor; GIS=GCSF Initiation Score (0 to 1 with 1 best); GPS=GCSF persistence score (0 to 1 with 1 best);


  • Absolute Neutrophil Count (ANC) at EP2006 Initiation [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 4: To describe hematological outcomes observed in association with primary and secondary prophylactic use of EP2006 in patients at risk for FN; including break-through episodes of FN.

  • Absolute Neutrophil Count (ANC) Across All Cycles [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 4: To describe hematological outcomes observed in association with primary and secondary prophylactic use of EP2006 in patients at risk for FN; including break-through episodes of FN.

  • Number of Patients With CIN/FN Episodes: Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 4: To describe hematological outcomes observed in association with primary and secondary prophylactic use of EP2006 in patients at risk for FN; including break-through episodes of FN.

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; Chemotherapy disturbance=dose reduction, delay, and/or cancellation; Composite (any of CIN grade 4, FN, CIN/FN-related hospitalization or CIN/FN-related chemotherapy disturbance)

    A patient may fall into more than one or none of the categories displayed.


  • CIN/FN Episodes: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 4: To describe hematological outcomes observed in association with primary and secondary prophylactic use of EP2006 in patients at risk for FN; including break-through episodes of FN.

    Chemotherapy-Induced Neutropenia (CIN); Febrile Neutropenia (FN); Chemotherapy disturbance=dose reduction, delay, and/or cancellation; Composite (any of CIN grade 4, FN, CIN/FN-related hospitalization [RH] or CIN/FN-related chemotherapy disturbance [RCD])


  • Incidence of Outcomes by Chemotherapy Risk: Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents incidences of different outcomes and composite outcome by chemotherapy risk group. ^Composite endpoint includes any of CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance.

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).


  • Incidence of CIN/FN-related Chemotherapy Disturbance by EP2006 Prophylaxis Type: Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).


  • Incidence of CIN/FN-related Hospitalization Outcomes by EP2006 Practice Patterns (Relative to Guidelines): Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents incidences of different outcomes and composite outcome by prophylaxis decision (relative to guidelines). ^Composite endpoint includes any of CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance.

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).


  • Incidence of CIN Grade 4 Episodes by EP2006 Dose: Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).


  • Incidence of Outcomes by Mean GIS: Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents incidences of outcomes by day (mean GIS over all visits). ^Composite outcome includes CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).


  • Incidence of Outcomes: Cycles Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents incidences of outcomes on a cycle level. ^Composite outcome includes CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).


  • Incidence of Outcomes by Day of Study Drug Initiation: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents incidences of outcomes on a cycle level by day of study drug initiation. ^Composite outcome includes CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010). *Day of EP2006 initiation- Day 0 (during chemotherapy); **Day of EP2006 initiation- Days 1-3 (per guidelines)


  • Incidence of Outcomes by Study Drug Duration: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents incidences of outcomes on a cycle level by study drug duration. ^Composite outcome includes CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia;


  • Number of Patients by Cause of Death [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]
    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

  • Number of Participants With All-cause Mortality by Any/no Grade 4 CIN and/or FN [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table shows number of patients that died in each group.

    CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia


  • Number of Participants With All-cause Mortality by CIN/FN-related Chemotherapy Disturbance [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table shows number of patients who died by any or no CIN/FN related chemotherapy disturbance.

    CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia


  • Number of Participants With Cancer-related Mortality by Any/no Grade 4 CIN or FN [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents number of patients that had a cancer-related death by any/no grade 4 CIN or FN

    CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia


  • Number of Participants With Cancer-related Mortality by Any CIN/FN-related Chemotherapy Disturbance [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents number of patients who had a cancer-related death by any/no CIN/FN-related chemotherapy disturbance

    CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia


  • Number of Participants With Any CIN/FN-related Chemotherapy Disturbance by Prophylaxis Type [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents number of patients with any CIN/FN-related chemotherapy disturbance by prophylaxis type.

    CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia


  • Number of Participants With Any CIN/FN-related Chemotherapy Disturbance by Treatment Decision [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents number of patients with any CIN/FN-related chemotherapy disturbances by treatment decision.

    CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia


  • Predictors of Absolute Neutrophil Count [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 6: To examine the multilevel determinants (patient, center) of hematological outcomes of primary and secondary prophylaxis with EP2006 to better understand the variability in outcomes achieved.

    Hierarchical modeling was used to test the relationship of patient- and physician/center-level variables and treatment response in terms of ANC. This analysis was conducted at the cycle level using a 1-cycle lag between treatment patterns and outcomes, that is study drug treatment patterns in one cycle predicted the ANC value at the beginning of the next cycle. Log-transformed ANC values were used.

    Table presents predictors for ANC: GCSF decision, study drug dose, tumor type, patient gender, ECOG, Hb

    Since log-transformed Absolute Neutrophil Count (ANC) values were used, Exp(beta) can be interpreted in terms of % change in ANC for each unit change in predictor or for each category relative to the referent (for categorical variables); Hb=Hemoglobin


  • Patient/Center-level Covariance Parameter Estimates of Absolute Neutrophil Count [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 6: To examine the multilevel determinants (patient, center) of hematological outcomes of primary and secondary prophylaxis with EP2006 to better understand the variability in outcomes achieved.

    Mean and standard error estimated from ANCOVA


  • EP2006 Day of Initiation: Cycle Distribution [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery.

    Table presents number of cycles by day after chemotherapy.


  • EP2006 Cycles by Treatment Duration [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]
    Objective 2: To describe EP2006 primary or secondary prophylaxis patterns for FN over up to 6 cycles of chemotherapy, with or without prior, concurrent, or later radiotherapy or surgery

  • Incidence of Outcomes [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 5: To describe the distribution of chemotherapy dose delays and reductions, surgery delays and cancellations, radiotherapy delays, dose reductions, and cancellations, and mortality (GCSF-related; FN-related; cancer-related; not related to GCSF, FN, or cancer; all-cause); and estimate the time-to-event for such events over the course of EP2006 treatment.

    Table presents incidences of different outcomes and composite outcome by chemotherapy risk group. ^Composite endpoint includes any of CIN grade 4, FN, CIN/FN-related hospitalization and CIN/FN-related chemotherapy disturbance.

    CIN: Chemotherapy-Induced Neutropenia; FN: Febrile Neutropenia; ANC: Absolute Neutrophil count; GIS: GCSF Initiation Score; Prophylaxis decision mentioned below are relative to EORTC guidelines (2010).



Secondary Outcome Measures:
  • Cohort Identification [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

    A two-group solution converged and the groups differentiated on key baseline variables. However, the group sizes were too unevenly distributed for further analysis with the "high risk group" comprised of only 3.0% of the evaluable sample.

    ANC=Absolute Neutrophil Count; CIN=Chemotherapy-Induced Neutropenia; FN=Febrile Neutropenia


  • Characteristics of Clusters: Hemoglobin Study Start [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]
    Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

  • Characteristics of Clusters: ECOG Performance Status [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

    ECOG score is a severity scale from 0 to 5 (highest) to grade toxicity and is defined as follows: 0=none, 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=lethal. ECOG is described in more detail by Oken et al, Am J Clin Oncol (CCT) 5:649-655, 1982.

    FN=Febrile Neutropenia; ECOG: European Cooperative Oncology Group


  • Characteristics of Clusters: Cancer Stage [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

    FN=Febrile Neutropenia


  • Characteristics of Clusters: History of Antibiotic Use for CIN [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

    CIN=Chemotherapy Induced Neutropenia; FN=Febrile Neutropenia


  • Characteristics of Clusters: Liver, Renal and/or Cardiovascular Disease [ Time Frame: Enrollment cycle. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician. ] [ Designated as safety issue: No ]

    Objective 7: To identify different latent clusters of end-stage cancer patients receiving chemotherapy and being treated with EP2006 for the treatment or primary or secondary prophylaxis of FN using statistical data-mining techniques to profile patients based on medical history, concomitant comorbid conditions, and current clinical status.

    FN=Febrile Neutropenia


  • Modeling Grade 4 CIN Episode: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006

    Only results with a p-value of <0.05 are added as statistical analyses appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; GCSF: granulocyte colony-stimulating factor; GIS: GCSF Initiation Score


  • Modeling Grade 4 CIN Episode: Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    H/o=History of; CI=confidence interval; CIN=chemotherapy-induced neutropenia


  • Modeling FN Episode: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia; ECOG: Eastern Cooperative Oncology Group


  • Modeling FN Episode: Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia


  • Modeling CIN/FN-related Hospitalization: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia; ECOG: Eastern Cooperative Oncology Group.


  • Modeling CIN/FN-related Hospitalization: Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia; ECOG: Eastern Cooperative Oncology Group.


  • Modeling CIN/FN-related Chemotherapy Disturbance: Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; GCSF: granulocyte colony-stimulating factor; GIS: GCSF Initiation Score; Chemotherapy disturbance=dose reduction, delay, and/or cancellation


  • Modeling CIN/FN-related Chemotherapy Disturbance: Patient Level (Patient-level Predictors) [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; FN: febrile neutropenia


  • Modeling Composite Outcome (Any of CIN Grade 4, FN, CIN/FN-related Hospitalization, CIN/FN-related Chemotherapy Disturbance): Cycle Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; ECOG: Eastern Cooperative Oncology Group; FN: febrile neutropenia; GCSF: granulocyte colony-stimulating factor; GIS: GCSF Initiation Score.


  • Modeling Composite Outcome (Any of CIN Grade 4, FN, CIN/FN-related Hospitalization, CIN/FN-related Chemotherapy Disturbance): Patient Level [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: No ]

    Objective 8: To model patient- and center-level variables between patients who responded and those who did not respond to primary or secondary prophylaxis with EP2006.

    Objective 9: To model patient- and center-level variables between patients who had chemotherapy dose delays or reductions, surgery delays and cancellations, and radiotherapy delays, dose reductions, or cancellations vs. no such events during the course of primary or secondary prophylaxis with EP2006.

    Only results with a p-value of <0.05 are shown in the statistical appendices.

    CI: confidence interval; CIN: chemotherapy-induced neutropenia; ECOG: Eastern Cooperative Oncology Group; FN: febrile neutropenia; GCSF: granulocyte colony-stimulating factor; GIS: GCSF Initiation Score. H/o repeated infections refers at enrollment; H/o: History of


  • Patient-level Predictors for All-cause Mortality [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]

    Objective 10: To model patient- and center-level variables between patients who died vs. survived during the course of primary or secondary prophylaxis with EP2006, in all patients and those with break-through FN episodes.

    Table presents patient-level predictors for all-cause mortality: history of anemia at enrollment, liver/renal/cardiac comorbidity, poor performance (ECOG >=2) during study


  • Patient-level Predictor for Cancer-related Mortality [ Time Frame: All cycles. Patients were evaluated at the enrollment cycle and then re-evaluated at each cycle for a maximum total of 6 cycles; however, the scheduling of these evaluations was left to the discretion of the physician, mean duration of study for 105 days ] [ Designated as safety issue: Yes ]

    Objective 10: To model patient- and center-level variables between patients who died vs. survived during the course of primary or secondary prophylaxis with EP2006 in all patients and those with break-through FN episodes.

    Table presents patient level predictors for cancer-related mortality: female gender, poor performance (ECOG >=2) during study.

    ECOG score is a severity scale from 0 to 5 (highest) to grade toxicity and is defined as follows: 0=none, 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=lethal. ECOG is described in more detail by Oken et al, Am J Clin Oncol (CCT) 5:649-655, 1982.



Enrollment: 1496
Study Start Date: March 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Only 1 group
Cancer patients treated with chemotherapy and who are prescribed commercially available filgrastim biosimilar for primary or secondary prophylaxis for FN.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Cancer patients treated with chemotherapy and who are prescribed commercially available filgrastim biosimilar (EP2006) for primary or secondary prophylaxis for febrile neutropenia.

Criteria

Inclusion Criteria:

  • Male or female adults (age > / = 18 years)
  • Diagnosed with one of the following types and stages of tumors: stage III or IV breast cancer; stage III or IV ovarian cancer; stage III or IV bladder cancer; stage III or IV lung cancer; metastatic prostate cancer; stage III or IV diffuse large B-cell lymphoma; multiple myeloma.
  • Planned to receive primary prophylaxis with filgrastim biosimilar (EP2006) at the first cycle of chemotherapy (regardless of line of chemotherapy); or receiving secondary prophylaxis with filgrastim biosimilar (EP2006) irrespective of chemotherapy cycle.
  • Treated with commercially available filgrastim biosimilar per physician's best clinical judgment and per current European filgrastim biosimilar (EP2006) label.
  • Female patients must be either post-menopausal for one year or surgically sterile or using effective contraceptive methods such as barrier method with spermicide or an intra-uterine device. Oral contraceptive use is allowed.
  • Informed written consent to participate in the study by patients or their legal guardian.

Exclusion Criteria:

  • Patients with myeloid malignancies, with the exception of multiple myeloma.
  • Sensitivity to filgrastim biosimilar or any other CSF.
  • Hypersensitivity to E. coli-derived proteins.
  • Radiotherapy to ≥ 20% of total body bone.
  • Infection within two weeks of starting current line of chemotherapy.
  • Patients with several medical condition(s) that in view of the investigator prohibits participation in the study.
  • Patients with willfully negligent nonadherence to their cancer treatment.
  • Use of any investigational agent in the 30 days prior to enrollment.
  • Women of childbearing potential not using the contraception method(s) described above.
  • Women who are breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459653

  Show 120 Study Locations
Sponsors and Collaborators
Sandoz
Investigators
Study Chair: Sandoz GmBH Sandoz GmbH
  More Information

No publications provided

Responsible Party: Sandoz
ClinicalTrials.gov Identifier: NCT01459653     History of Changes
Other Study ID Numbers: EP06-502
Study First Received: August 30, 2011
Results First Received: March 26, 2015
Last Updated: July 7, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Romania: National Medicines Agency
Czech Republic: State Institute for Drug Control

Keywords provided by Sandoz:
Febrile neutropenia
cancer
chemotherapy,
primary prophylaxis
secondary prophylaxis
filgrastim
granulocyte colony stimulating factor
observational study
noninterventional study

Additional relevant MeSH terms:
Chemotherapy-Induced Febrile Neutropenia
Febrile Neutropenia
Fever
Lymphoma, B-Cell
Multiple Myeloma
Neutropenia
Agranulocytosis
Blood Protein Disorders
Body Temperature Changes
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Leukocyte Disorders
Leukopenia
Lymphatic Diseases
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Signs and Symptoms
Vascular Diseases
Lenograstim
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on August 02, 2015