Prospective Observational Study of Febrile Neutropenia (FN) and Pegfilgrastim Primary Prophylaxis in Breast Cancer and Non-Hodgkin's Lymphoma Patients Receiving High (>20%) FN-risk Chemotherapy

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02178475

Enrollment

943

Registered

2014-06-30

Start date

2014-07-18

Completion date

2016-10-28

Last updated

2018-07-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chemotherapy-induced Febrile Neutropenia

Keywords

NHL, Breast Cancer

Brief summary

To estimate the incidence of febrile neutropenia in patients with breast cancer and non-Hodgkin's lymphoma receiving high (\> 20%) FN-risk chemotherapy and pegfilgrastim primary prophylaxis.

Interventions

None listed

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age ≥ 18 years old. * Any stage NHL or breast cancer and received the first cycle of a new chemotherapy course. * Received the first cycle of a permitted standard dose chemotherapy regimens with an estimated high (\> 20%) FN risk according to published data or guidelines (dose modifications +/-10% in Cycle 1 are allowable). * Initiated treatment in Cycle 1 with pegfilgrastim according to the pegfilgrastim summary of product characteristics. (SmPC). Enrolment must occur after the first pegfilgrastim dosing in Cycle 1 and before the second day of Cycle 2.

Exclusion criteria

* Ongoing or planned concurrent participation in any clinical study involving Investigational Product that has not been approved by the national competent authorities for any indication. * Ongoing or planned concurrent participation in any clinical study where the administration of Colony Stimulating Factor (CSF) is determined by the protocol (clinical trials on an approved drug and observational trials are permitted as long as these do not mandate how neutropenia should be treated).

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Febrile Neutropenia	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	Febrile neutropenia (FN) was defined as an absolute neutrophil count (ANC) of \< 0.5 x 10\^9/L, or \< 1.0 x 10\^9/L predicted to fall below 0.5 x 10\^9/L within 48 hours with fever or clinical signs of sepsis; fever and ANC were measured the same day or within ± 1 calendar day.

Secondary

Measure	Time frame	Description
Number of Participants Who Discontinued G-CSF Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	Participants who discontinued G-CSF prophylaxis was defined as participants who received at least one cycle of chemotherapy (cycle 2 or later) in which no G-CSF prophylaxis was administered. Discontinuation was categorized as either temporary (participant received G-CSF prophylaxis in at least one subsequent cycle) or permanent (participant had at least one cycle of chemotherapy following the cycle in which no G-CSF prophylaxis was administered, and no G-CSF prophylaxis was administered in any subsequent cycle, OR participant did not receive G-CSF prophylaxis in the last cycle of chemotherapy).
Characteristics of Participants Who Discontinued Pegfilgrastim Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	Participants who discontinued pegfilgrastim prophylaxis are participants who received at least one cycle of chemotherapy (cycle 2 or later) in which pegfilgrastim prophylaxis was not administered, but other G-CSF prophylaxis was administered in this cycle. Participants in this group received either pegfilgrastim or other G-CSF prophylaxis in all chemotherapy cycles. Data includes both temporary and permanent pegfilgrastim discontinuation.
Characteristics of Participants Who Discontinued G-CSF Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	Participants who discontinued G-CSF prophylaxis are participants who received at least one cycle of chemotherapy (cycle 2 or later) in which no G-CSF prophylaxis was administered. Data includes both temporary and permanent discontinuation of G-CSF prophylaxis.
Number of Cycles With No Pegfilgrastim Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	A cycle of chemotherapy (cycle 2 or later) in which pegfilgrastim prophylaxis was not administered, but other G-CSF prophylaxis was administered in this cycle.
Number of Cycles With no G-CSF Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	A cycle of chemotherapy (cycle 2 or later) in which no G-CSF prophylaxis was administered.
Reasons for Discontinuation of Pegfilgrastim Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	Participants who discontinued pegfilgrastim prophylaxis are participants who received at least one cycle of chemotherapy (cycle 2 or later) in which pegfilgrastim prophylaxis was not administered, but other G-CSF prophylaxis was administered in this cycle. Participants in this group received either pegfilgrastim or other G-CSF prophylaxis in all chemotherapy cycles. Data includes both temporary and permanent pegfilgrastim discontinuation.
Reasons for Discontinuation of G-CSF Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	Participants who discontinued G-CSF prophylaxis are participants who received at least one cycle of chemotherapy (cycle 2 or later) in which no G-CSF prophylaxis was administered. Data includes both temporary and permanent discontinuation of G-CSF prophylaxis. Participants may have more than 1 discontinuation reason.
Number of Participants Who Discontinued Pegfilgrastim Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	Participants who discontinued pegfilgrastim prophylaxis was defined as participants who received at least one cycle of chemotherapy (cycle 2 or later) in which pegfilgrastim prophylaxis was not administered, but other granulocyte colony-stimulating factor (G-CSF) prophylaxis was administered. Participants in this group received either pegfilgrastim or other G-CSF prophylaxis in all chemotherapy cycles. Discontinuation was categorized as either temporary (participant received pegfilgrastim prophylaxis in at least one subsequent cycle) or permanent (participant had at least one cycle of chemotherapy following the cycle in which no pegfilgrastim prophylaxis was administered, and other G-CSF prophylaxis (i.e. not pegfilgrastim) was administered in all subsequent cycles, OR participant did not receive pegfilgrastim prophylaxis in the last cycle of chemotherapy, and other G-CSF prophylaxis was administered).
Number of Febrile Neutropenia Events That Occurred During Cycles With No G-CSF Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	The number of febrile neutropenia events that occurred during a cycle of chemotherapy (cycle 2 or later) in which no G-CSF prophylaxis was administered. Febrile neutropenia was defined as an ANC of \< 0.5 x 10\^9/L, or \< 1.0 x 10\^9/L predicted to fall below 0.5 x 10\^9/L within 48 hours with fever or clinical signs of sepsis; fever and ANC were measured the same day or within ± 1 calendar day.
Number of Participants Who Experienced Febrile Neutropenia During Cycles With No G-CSF Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	The number of participants who received at least one cycle of chemotherapy in which no G-CSF prophylaxis was administered who experienced febrile neutropenia during a cycle of chemotherapy in which no G-CSF prophylaxis was administered. Febrile neutropenia was defined as an ANC of \< 0.5 x 10\^9/L, or \< 1.0 x 10\^9/L predicted to fall below 0.5 x 10\^9/L within 48 hours with fever or clinical signs of sepsis; fever and ANC were measured the same day or within ± 1 calendar day.
Number of Participants Who Experienced Complications of Febrile Neutropenia During Cycles With No G-CSF Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	The number of participants who received at least one cycle of chemotherapy in which no G-CSF prophylaxis was administered who experienced complications of febrile neutropenia during a cycle of chemotherapy in which no G-CSF prophylaxis was administered. Complications of febrile neutropenia were defined as FN-related hospitalizations and death, and neutropenia-related chemotherapy dose delays and dose reductions.
Number of Cycles With No G-CSF Prophylaxis in Which Febrile Neutropenia Events Occurred	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	The number of chemotherapy cycles during which an event of febrile neutropenia occurred in which no G-CSF prophylaxis was administered. Febrile neutropenia was defined as an ANC of \< 0.5 x 10\^9/L, or \< 1.0 x 10\^9/L predicted to fall below 0.5 x 10\^9/L within 48 hours with fever or clinical signs of sepsis; fever and ANC were measured the same day or within ± 1 calendar day.
Number of Cycles With No G-CSF Prophylaxis in Which Complications of Febrile Neutropenia Occurred	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	The number of chemotherapy cycles during which complications of febrile neutropenia occurred in which no G-CSF prophylaxis was administered. Complications of febrile neutropenia were defined as FN-related hospitalizations and death, and neutropenia-related chemotherapy dose delays and dose reductions.
Number of Participants Who Permanently Switched From Pegfilgrastim Prophylaxis to Other G-CSF Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	The number of participants who received pegfilgrastim prophylaxis from cycle 1 until a cycle when other G-CSF prophylaxis was administered, and this G-CSF or a different G-CSF agent (not pegfilgrastim) was received as prophylaxis at each remaining cycle of the chemotherapy course.
Characteristics of Participants Who Received On-schedule Pegfilgrastim Primary Prophylaxis	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	On-schedule pegfilgrastim primary prophylaxis was defined as participants who received pegfilgrastim in cycle 1 and continued to receive pegfilgrastim across all cycles, administered 1-3 days after the end of cytotoxic chemotherapy in each cycle.
Percentage of Participants Who Experienced Complications of Febrile Neutropenia	Participants were followed for up to 8 cycles of chemotherapy; the average observation time was 4.1 months.	Complications of febrile neutropenia were defined as FN-related hospitalizations and death, and neutropenia-related chemotherapy dose delays and dose reductions.

Countries

Austria, Belgium, Bulgaria, Czechia, France, Germany, Greece, Poland, Romania

Participant flow

Recruitment details

The study was conducted at 66 centers in Austria, Belgium, Bulgaria, Czech Republic, France, Germany, Greece, Poland, and Romania. The first participant enrolled on 18 July 2014 and the last participant enrolled on 28 April 2016.

Pre-assignment details

Participants were enrolled at sites where they were receiving treatment as part of their routine standard of care. No specific interventional tests, investigations, procedures or changes to routine practice were conducted as part of this study.

Participants by arm

Arm	Count
Chemotherapy + Pegfilgrastim Patients with non-Hodgkin's lymphoma or breast cancer being treated with a permitted standard-dose chemotherapy regimen with a high FN risk (\> 20%) and who had pegfilgrastim prophylaxis initiated in the first cycle of chemotherapy.	844
Total	844

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	13
Overall Study	Lost to Follow-up	10
Overall Study	Protocol-specified Criteria	99
Overall Study	Withdrawal by Subject	7

Baseline characteristics

Characteristic	Chemotherapy + Pegfilgrastim
Age, Continuous	57.2 years STANDARD_DEVIATION 12.2
Age, Customized < 65 years	563 Participants
Age, Customized ≥ 65 years	281 Participants
Baseline Comorbidities Cardiovascular disease	211 participants
Baseline Comorbidities COPD/Pulmonary disease	41 participants
Baseline Comorbidities Current infection	8 participants
Baseline Comorbidities Diabetes mellitus	75 participants
Baseline Comorbidities Liver disease	18 participants
Baseline Comorbidities Open wound	3 participants
Baseline Comorbidities Renal disease/impaired clearance	16 participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active)	645 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restrictive but ambulatory)	129 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (Ambulatory but unable to work)	14 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3 (Limited self-care)	6 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 4 (Disabled, confined to bed/chair)	1 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	49 Participants
History of Febrile Neutropenia No	839 Participants
History of Febrile Neutropenia Yes	5 Participants
Race/Ethnicity, Customized Black	4 Participants
Race/Ethnicity, Customized Missing	166 Participants
Race/Ethnicity, Customized Other	1 Participants
Race/Ethnicity, Customized White	673 Participants
Sex: Female, Male Female	723 Participants
Sex: Female, Male Male	121 Participants
Tumor Type Breast cancer	654 Participants
Tumor Type Non-Hodgkin's lymphoma (NHL)	190 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	11 / 844
serious Total, serious adverse events	5 / 844

Outcome results

Primary

Percentage of Participants With Febrile Neutropenia

Febrile neutropenia (FN) was defined as an absolute neutrophil count (ANC) of \< 0.5 x 10\^9/L, or \< 1.0 x 10\^9/L predicted to fall below 0.5 x 10\^9/L within 48 hours with fever or clinical signs of sepsis; fever and ANC were measured the same day or within ± 1 calendar day.