A Study of Neutropenia and Anemia Management in Patients With Solid Tumors Receiving Myelotoxic Chemotherapy

Study Overview
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Brief Summary
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The primary objective was to describe the incidence of febrile neutropenia based on granulocyte-colony stimulating factor (G-CSF) use (primary, secondary, treatment, or no usage) in patients receiving myelotoxic chemotherapy.

Detailed Description
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This is a multi-center international observational study of patients receiving myelotoxic regimens, with an investigator assessed risk of febrile neutropenia ≥ 20%, for the treatment of solid tumors (breast, ovarian and lung). This is an observational study in which patient risk factors were qualitatively (but not quantitatively) assessed, and adherence to G-CSF primary prophylaxis was at the discretion of physicians and not mandated by the protocol.

Official Title
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A Prospective Observational Study of Neutropenia and Anemia Management in Subjects With Solid Tumors Receiving Myelotoxic Chemotherapy

Conditions
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Breast Cancer, Non-Small Cell Lung Cancer, Ovarian Cancer, Small Cell Lung Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects greater than or equal to 18 years old with breast, ovarian or lung cancer receiving chemotherapy in any schedule, e.g. dose dense or standard chemotherapy. These subjects must have an Investigator assessed risk of febrile neutropenia (FN) ≥20% (based on 2006 European Organisation for Research and Treatment of Cancer (EORTC) G-CSF Guidelines Exclusion Criteria: - Subjects with concurrent administration of radiotherapy are not eligible (previous radiotherapy is permitted if terminated at least 2 weeks prior to commencing applicable chemotherapy in this study).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Febrile Neutropenia (FN) | Febrile neutropenia was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Who Received No Prophylaxis or Treatment With Granulocyte Colony-stimulating Factors (G-CSF) Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Assignment to G-CSF use groups was programmatically derived rather than assigned by the investigator. Participants in the No G-CSF use group received no G-CSF prophylaxis or treatment at any time during cycles 1 to 8. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Primary Prophylaxis With Pegfilgrastim Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Primary prophylaxis with pegfilgrastim was defined as receiving pegfilgrastim starting in cycle 1 on day 1 to 7 if chemotherapy completed by day 7 and day 1 to 11 if chemotherapy completed after day 7. Assignment to G-CSF use groups was programmatically derived rather than assigned by the investigator. Participants were assigned to a G-CSF use group that represented the 'best' G-CSF therapy they received at any point in the study. Participants who received G-CSF support from the beginning of Cycle 1 were assigned to primary prophylaxis regardless of whether they continued to receive G-CSF support in subsequent cycles. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Primary Prophylaxis With Any Daily G-CSF Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Primary prophylaxis was defined as receiving any daily G-CSF (e.g. filgrastim or lenograstim) starting in cycle 1 on day 1 to 7 if chemotherapy completed by day 7 and day 1 to 11 if chemotherapy completed after day 7. Assignment to G-CSF use groups was programmatically derived rather than assigned by the investigator. Participants were assigned to a G-CSF use group that represented the 'best' G-CSF therapy they received at any point in the study. Participants who received G-CSF support from the beginning of cycle 1 were assigned to primary prophylaxis regardless of whether they continued to receive G-CSF support in subsequent cycles. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Secondary Prophylaxis With Pegfilgrastim Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Secondary prophylaxis with pegfilgrastim was defined as receiving pegfilgrastim starting in cycle 2 onwards on day 1 to 7 if chemotherapy completed by day 7 and day 1 to 11 if chemotherapy completed after day 7. Assignment to G-CSF use groups was programmatically derived rather than assigned by the investigator. Participants were assigned to a G-CSF use group that represented the 'best' G-CSF therapy they received at any point in the study. Adherence of G-CSF support in subsequent cycles was not required for secondary prophylaxis; just an initiation of pegfilgrastim support in the beginning of cycle 2 or later. Results include the FN event that may have triggered the secondary prophylaxis treatment. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Secondary Prophylaxis With Any Daily G-CSF Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Secondary prophylaxis was defined as receiving any daily G-CSF starting in cycle 2 onwards on day 1 to 7 if chemotherapy completed by day 7 and day 1 to 11 if chemotherapy completed after day 7. Assignment to G-CSF use groups was programmatically derived rather than assigned by the investigator. Participants were assigned to a G-CSF use group that represented the 'best' G-CSF therapy they received at any point in the study. Adherence of G-CSF support in subsequent cycles was not required for secondary prophylaxis; just an initiation of G-CSF support in the beginning of cycle 2 or later. Results include the FN event that may have triggered the secondary prophylaxis treatment. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Primary Prophylaxis With an Other G-CSF Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Primary prophylaxis was defined as receiving any other G-CSF starting in cycle 1 on day 1 to 7 if chemotherapy completed by day 7 and day 1 to 11 if chemotherapy completed after day 7. Assignment to G-CSF use groups was programmatically derived rather than assigned by the investigator. Participants were assigned to a G-CSF use group that represented the 'best' G-CSF therapy they received at any point in the study. Participants who received G-CSF support from the beginning of cycle 1 were assigned to primary prophylaxis regardless of whether they continued to receive G-CSF support in subsequent cycles. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Secondary Prophylaxis With an Other G-CSF Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Secondary prophylaxis was defined as receiving any daily G-CSF starting in cycle 2 onwards on day 1 to 7 if chemotherapy completed by day 7 and day 1 to 11 if chemotherapy completed after day 7. Assignment to G-CSF use groups was programmatically derived rather than assigned by the investigator. Participants were assigned to a G-CSF use group that represented the 'best' G-CSF therapy they received at any point in the study. Adherence of G-CSF support in subsequent cycles was not required for secondary prophylaxis; just an initiation of G-CSF support in the beginning of cycle 2 or later. Results include the FN event that may have triggered the secondary prophylaxis treatment. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Treatment With Pegfilgrastim Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Treatment with pegfilgrastim is defined as participants who started pegfilgrastim treatment after day 7 of any cycle if chemotherapy completed by day 7 and after day 11 of any cycle if chemotherapy completed after day 7. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Treatment With Any Daily G-CSF Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Treatment with any daily G-CSF is defined as participants who started daily G-CSF treatment after day 7 of any cycle if chemotherapy completed by day 7 and after day 11 of any cycle if chemotherapy completed after day 7. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Receiving Treatment With Any Other G-CSF Who Experienced Febrile Neutropenia | FN was defined as a single oral temperature ≥ 38.3°C, or a temperature of ≥ 38.0°C for ≥ 1 hour with a neutrophil count of < 500 cells/mm² or < 1000 cells/mm² and predicted to fall below 500 cells/mm². Treatment with any other G-CSF is defined as participants who started other G-CSF treatment after day 7 of any cycle if chemotherapy completed by day 7 and after day 11 of any cycle if chemotherapy completed after day 7. | Cycles 1 - 8 (approximately 24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Received G-CSF During Cycles 1 to 8 |  | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Days of Prophylaxis in Participants Receiving Primary Prophylaxis With Pegfilgrastim | The average number of days of pegfilgrastim use per cycle was calculated across all administered cycles. | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Days of Prophylaxis in Participants Receiving Primary Prophylaxis With Any Daily G-CSF | The average number of days of daily G-CSF use per cycle was calculated across all administered cycles. | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Days of Prophylaxis in Participants Receiving Secondary Prophylaxis With Pegfilgrastim | The average number of days of pegfilgrastim use per cycle was calculated across all administered cycles. | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Days of Prophylaxis in Participants Receiving Secondary Prophylaxis With Any Daily G-CSF | The average number of days of daily G-CSF use per cycle was calculated across all administered cycles. | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Days of Treatment in Participants Receiving Treatment With Pegfilgrastim | The average number of days of pegfilgrastim use per cycle was calculated across all administered cycles. | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Days of Treatment in Participants Receiving Treatment With Any Daily G-CSF |  | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants With Chemotherapy Dose Delays in Cycles 2 Through 8 | A dose delay is defined as a delay of more than 3 days in the start of chemotherapy measured since the start of the previous cycle. The percentage of participants with delays in chemotherapy administration are summarized by the length of delay (> 3 days, > 5 days, and > 7 days) across cycles 2 through 8. | Cycles 2 - 8 (approximately 21 weeks) | 
| Percentage of Cycles With Chemotherapy Dose Delays | A dose delay is defined as a delay of > 3 days in the start of chemotherapy measured since the start of the previous cycle. The percentage of cycles delayed are summarized by the length of delay (> 3 days, > 5 days, and > 7 days) across cycles 2 through 8. | Cycles 2 - 8 (approximately 21 days) | 
| Percentage of Participants With Chemotherapy Dose Reductions | A participant is considered to have a dose reduction in a given cycle if there was a ≥ 15% reduction in dose of any chemotherapy agent planned for that cycle, relative to the dose planned at the baseline visit for that cycle. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Cycles With Chemotherapy Dose Reductions | A dose reduction in a given cycle is defined as a ≥ 15% reduction in dose of any chemotherapy agent planned for that cycle, relative to the dose planned at the baseline visit for that cycle. | Cycles 1 - 8 (approximately 24 weeks) | 
| Reasons for Cycles With > 3 Days Chemotherapy Dose Delays in Cycles 2 to 8 | A dose delay is defined as a delay of > 3 days in the start of chemotherapy measured since the start of the previous cycle. | Cycles 2 - 8 (approximately 21 weeks) | 
| Reasons for Cycles With ≥ 15% Chemotherapy Dose Reductions in Cycles 1-8 | A dose reduction in a given cycle is defined as a ≥ 15% reduction in dose of any chemotherapy agent planned for that cycle, relative to the dose planned at the baseline visit for that cycle. | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Participants With Systemic Anti-infective Use in Cycles 1 to 8 | Number of participants with systemic anti-infective use, including antibiotics, anti-fungal and virostatic for prophylaxis or treatment. | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Participants With Unplanned Hospitalizations | Unplanned hospitalizations included only those which involved an overnight stay and occurred in cycles 1 to 8. | Cycles 1 - 8 (approximately 24 weeks) | 
| Investigator Assessed Clinical Response at End of Treatment |  | End of treatment (approximately 24 weeks) | 
| Number of Participants With Hematological Toxicities | The number of participants experiencing treatment related grade 3 and 4 hematological toxicities during cycles 1 to 8. Participants experiencing both Grade 3 and Grade 4 toxicities are reported under Grade 4 only (maximum toxicity). Toxicity grades for hematology data are defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0: Absolute neutrophil count (ANC) - Grade 3: < 1.0 - 0.5 x 10^9/L; ANC - Grade 4: < 0.5 x 10^9/L; White blood cells (WBC) - Grade 3: < 2.0 - 1.0 x 10^9/L; WBC - Grade 4: < 1.0 x 10^9/L; Hemoglobin - Grade 3: < 8.0 - 6.5 g/dL; Hemoglobin - Grade 4: < 6.5 g/dL; Platelets - Grade 3: < 50 - 25 x 10^9/L; Platelets - Grade 4: < 25 x 10^9/L. | Cycles 1 - 8 (approximately 24 weeks) | 
| Time to Disease Progression | Time to disease progression was calculated from cycle 1 day 1 to a date at which disease progression was first recorded. Participants who died due to causes other than disease progression were censored at the date of death. Participants who were alive and whose disease had not progressed at the most recent contact, or who were lost to follow-up, or with missing data, were censored at the date of last contact. Median time to disease progression was estimated from the Kaplan-Meier survival function. | From cycle 1, day 1 until end of the long-term follow-up; median time on follow-up from cycle 1, day 1 was 52 months. | 
| Duration of Treatment With Erythropoiesis-stimulating Agents (ESAs) |  | Cycles 1 - 8 (approximately 24 weeks) | 
| Reason for Treatment With Erythropoiesis-stimulating Agents | The reason treatment with an ESA was initiated as recorded by the investigator; participants may have more than one reason for initiating treatment. | Cycles 1 - 8 (approximately 24 weeks) | 
| Hemoglobin Level at Initiation of Erythropoiesis-stimulating Agent Treatment |  | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Clinical Visits in Cycles 1-8 by ESA Use | The average number of clinical visits per month (28 day period) during cycles 1 to 8 and during the period of ESA treatment in cycles 1 to 8. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Who Received ESAs and Required a Red Blood Cell (RBC) Transfusion After 5 Weeks of ESA Treatment | Kaplan-Meier estimate of the percentage of participants with RBC transfusions from five weeks post initiation of ESA treatment until the end of ESA treatment during cycles 1 to 8. | From 5 weeks post initiation of ESA treatment to the end of ESA treatment phase (EOTP) during cycles 1 - 8; maximum duration of ESA treatment was 23 weeks. | 
| Change in Hemoglobin During ESA Treatment Phase |  | Initiation of ESA treatment (last assessment on or prior to ESA day 1) and at end of ESA treatment; median duration of ESA treatment was 4 weeks, maximum was 23 weeks. | 
| Percentage of Participants Who Received ESAs and Achieved Hematopoietic Response | Kaplan-Meier estimate of the percentage of participants in cycles 1 to 8 receiving ESA treatment who achieved a hematopoietic response during the ESA treatment phase, defined as a hemoglobin concentration ≥ 12 g/dL or a ≥ 2 g/dL rise in hemoglobin after starting ESA treatment. | Cycles 1 - 8 (approximately 24 weeks) | 
| Percentage of Participants Who Received ESAs and Achieved Hemoglobin ≥ 9 g/dL After 5 Weeks ESA Treatment | Kaplan-Meier estimate of the percentage of participants achieving a hemoglobin level ≥ 9 g/dL during the period from five weeks after initiation of ESA treatment until the end of ESA treatment during cycles 1 to 8. | From 5 weeks post initiation of ESA treatment to the end of ESA treatment phase (EOTP) during cycles 1 - 8; maximum duration of ESA treatment was 23 weeks. | 
| Percentage of Participants Who Received ESAs and Achieved Hemoglobin ≥ 10 g/dL After 5 Weeks ESA Treatment | Kaplan-Meier estimate of the percentage of participants achieving a hemoglobin level ≥ 10 g/dL during the period from five weeks after initiation of ESA treatment until the end of ESA treatment during cycles 1 to 8. | From 5 weeks post initiation of ESA treatment to the end of ESA treatment phase (EOTP) during cycles 1 - 8; maximum duration of ESA treatment was 23 weeks. | 
| Percentage of Participants Who Received ESAs and Achieved Hemoglobin ≥ 11 g/dL After 5 Weeks ESA Treatment | Kaplan-Meier estimate of the percentage of participants achieving a hemoglobin level ≥ 11 g/dL during the period from five weeks after initiation of ESA treatment until the end of ESA treatment during cycles 1 to 8. | From 5 weeks post initiation of ESA treatment to the end of ESA treatment phase (EOTP) during cycles 1 - 8; maximum duration of ESA treatment was 23 weeks. | 
| Percentage of Participants Who Received ESAs and Achieved Hemoglobin ≥ 12 g/dL After 5 Weeks ESA Treatment | Kaplan-Meier estimate of the percentage of participants achieving a hemoglobin level ≥ 12 g/dL during the period from five weeks after initiation of ESA treatment until the end of ESA treatment during cycles 1 to 8. | From 5 weeks post initiation of ESA treatment to the end of ESA treatment phase (EOTP) during cycles 1 - 8; maximum duration of ESA treatment was 23 weeks. | 
| Percentage of Participants Who Received ESAs and Achieved Hemoglobin From 10 to 12 g/dL After 5 Weeks ESA Treatment | Kaplan-Meier estimate of the percentage of participants achieving a hemoglobin level from 10 to 12 g/dL during the period from five weeks after initiation of ESA treatment until the end of ESA treatment during cycles 1 to 8. | From 5 weeks post initiation of ESA treatment to the end of ESA treatment phase (EOTP) during cycles 1 - 8; maximum duration of ESA treatment was 23 weeks. | 
| Percentage of Participants Who Received ESAs and Achieved Hemoglobin From 12 to 13 g/dL After 5 Weeks ESA Treatment | Kaplan-Meier estimate of the percentage of participants achieving a hemoglobin level from 12 to 13 g/dL during the period from five weeks after initiation of ESA treatment until the end of ESA treatment during cycles 1 to 8. | From 5 weeks post initiation of ESA treatment to the end of ESA treatment phase (EOTP) during cycles 1 - 8; maximum duration of ESA treatment was 23 weeks. | 
| Percentage of Participants Who Received ESAs and Achieved Hemoglobin From 10 to 12 g/dL 9 Weeks After Initiation of ESA Treatment | The percentage of participants achieving a hemoglobin level from 10 to 12 g/dL after 9 weeks of ESA treatment. | 9 weeks post initiation of ESA treatment | 
| Number of Participants With Systemic Transfusions in Cycles 1 to 8 | Number of participants who received transfusions, including platelets, packed red blood cells, whole blood, or other, during cycles 1 to 8. | Cycles 1 - 8 (approximately 24 weeks) | 
| Number of Transfusions Per Participant in Cycles 1 to 8 |  | Cycles 1 - 8 (approximately 24 weeks) |