N/A
N=1,496
Multi-level Evaluation of Chemotherapy-induced Febrile Neutropenia Prophylaxis, Outcomes, and Determinants With Granulocyte-colony Stimulating Factor
Febrile Neutropenia · Cancer · Breast Cancer · Ovarian Cancer · Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01459653 ↗Enrolled (actual)
1,496
Serious AEs
0.3%
Results posted
Jul 2015
Primary outcome: Primary: Chemotherapy Toxicity (%FN Risk) — 154; 650; 640; 3 participants
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- —
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Sandoz
- Primary completion
- Aug 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Chemotherapy Toxicity (%FN Risk) |
154; 650; 640; 3 | — |
| PRIMARY Cancer Treatment Type - Ever Received During Study |
100; 102; 85; 89; 31; 98 | — |
| PRIMARY Fever and Infections Ever During the Study |
76; 231 | — |
| PRIMARY Clinical Events Ever During Study (Frequency Threshold: 5%) |
357; 230; 222; 210; 200; 178 | — |
| PRIMARY Type of EP2006 Prophylaxis |
1046; 401; 245; 156 | — |
| PRIMARY Type of EP2006 Prophylaxis by Gender |
397; 649; 164; 237 | 0.3038 |
| PRIMARY Type of EP 2006 Prophylaxis by Age Group |
626; 420; 223; 178 | 0.1432 |
| PRIMARY Type of EP 2006 Prophylaxis by Tumor Type |
801; 245; 316; 85 | 0.6483 |
| PRIMARY Concomitant Antibiotic Prophylaxis |
175; 1261; 11 | — |
| PRIMARY EP2006 Dose (All Cycles) |
3182; 2756; 48 | — |
| PRIMARY EP2006 Dose (Enrollment Cycle) |
815; 610; 9 | — |
| PRIMARY EP2006 Dose (Cycle 1) |
593; 434; 9 | — |
| PRIMARY EP2006 Dose (Cycle 2) |
627; 507; 9 | — |
| PRIMARY EP2006 Dose (Cycle 3) |
597; 519; 9 | — |
| PRIMARY EP2006 Dose (Cycle 4) |
548; 490; 7 | — |
| PRIMARY EP2006 Dose (Cycle 5) |
431; 424; 7 | — |
| PRIMARY EP2006 Dose (Cycle 6) |
386; 382; 7 | — |
| PRIMARY EP2006 Dose by Patient Weight: Cycle Level |
1501; 1681; 771; 1985 | <0.0001 sig |
| PRIMARY EP2006 Dose by Tumor Type: Cycle Level |
2296; 886; 2313; 443 | <0.0001 sig |
| PRIMARY Patient Weight by Tumor Type (Solid Tumor vs. Hematological Tumor) |
441; 135; 676; 195 | 0.7509 |
| PRIMARY EP2006 Dose by Chemotherapy Toxicity: Cycle Level |
357; 1375; 1441; 189; 1159; 1402 | 0.0067 sig |
| PRIMARY EP2006 Day of Initiation: All Cycles |
3.1 | — |
| PRIMARY EP2006 Day of Initiation: Cycle 1 |
3.4 | — |
| PRIMARY EP2006 Day of Initiation: Cycle 2 |
3.1 | — |
| PRIMARY EP2006 Day of Initiation: Cycle 3 |
3.0 | — |
| PRIMARY EP2006 Day of Initiation: Cycle 4 |
3.0 | — |
| PRIMARY EP2006 Day of Initiation: Cycle 5 |
2.9 | — |
| PRIMARY EP2006 Day of Initiation: Cycle 6 |
3.0 | — |
| PRIMARY EP2006 Day of Initiation by Tumor Type (Solid Tumor vs. Hematological Tumor): Cycle Level |
2.6; 4.8 | <0.0001 sig |
| PRIMARY EP2006 Day of Initiation by Prophylaxis Type: Cycle Level |
3.2; 2.6 | 0.0103 sig |
| PRIMARY EP2006 Day of Initiation by Chemotherapy Toxicity: Cycle Level |
2.3; 3.0; 3.3 | <0.0001 sig |
| PRIMARY EP2006 Treatment Duration in Any Cycle |
5.1 | — |
| PRIMARY EP2006 Treatment Duration in Cycle 1 |
5.2 | — |
| PRIMARY EP2006 Treatment Duration in Cycle 2 |
5.1 | — |
| PRIMARY EP2006 Treatment Duration in Cycle 3 |
5.2 | — |
| PRIMARY EP2006 Treatment Duration in Cycle 4 |
5.1 | — |
| PRIMARY EP2006 Treatment Duration in Cycle 5 |
5.1 | — |
| PRIMARY EP2006 Treatment Duration in Cycle 6 |
5.0 | — |
| PRIMARY EP2006 Duration by Tumor Type: Cycle Level |
5.14; 5.03 | 0.0677 |
| PRIMARY EP2006 Duration by Prophylaxis Type: Cycle Level |
5.1; 5.2 | 0.8968 |
| PRIMARY EP2006 Duration by Chemotherapy Toxicity: Cycle Level |
4.6; 5.0; 5.3 | <0.0001 sig |
| PRIMARY Percentage of Patients With Each EORTC-identified Risk Factors for FN at Baseline |
41.3; 13.7; 1.9; 87.8; 13.1; 61.2 | — |
| PRIMARY Percentage of Patients With Each EORTC-identified Risk Factors for FN in Patients With Chemotherapy Risk 10-20% at Baseline |
44.6; 20.8; 2.0; 91.3; 13.3; 57.8 | — |
| PRIMARY Patient Risk Score (PRS) for All Patients |
2.9 | — |
| PRIMARY Patient Risk Score (PRS) for Patients Receiving Chemotherapy With 10-20% FN Risk by Tumor Type |
3.3; 3.2; 3.4 | — |
| PRIMARY Percentage of Patients With Each Prophylaxis Decision by Chemotherapy-associated FN Risk |
35.0; 17.3; 0; 0; 13.0; 6.9 | — |
| PRIMARY Percentage of Patients With Each Chemotherapy Risk Score (CRS) Result by Tumor Type |
17.3; 16.3; 21.0; 82.5; 83.7; 79.0 | 0.2698 |
| PRIMARY EP2006 Day of Initiation Relative to Guidelines by Cancer Type |
178; 1410; 624; 305; 691; 225 | <0.0001 sig |
| PRIMARY GCSF Initiation Score (GIS) |
15.9; 11.5; 16.6; 56.0 | — |
| PRIMARY GCSF Persistence Score (GPS) |
123; 2; 3; 2; 4; 1 | — |
| PRIMARY GCSF Congruence Score (GCS) |
2.5; 2.5; 2.5 | — |
| PRIMARY Absolute Neutrophil Count (ANC) at EP2006 Initiation |
4429.7 | — |
| PRIMARY Absolute Neutrophil Count (ANC) Across All Cycles |
4585.6 | — |
| PRIMARY Number of Patients With CIN/FN Episodes: Patient Level |
504; 332; 191; 86; 88; 138 | — |
| PRIMARY CIN/FN Episodes: Cycle Level |
1083; 602; 294; 105; 111; 174 | — |
| PRIMARY Incidence of Outcomes by Chemotherapy Risk: Patient Level |
7.8; 11.8; 15.9; 3.9; 3.5; 8.9 | — |
| PRIMARY Incidence of CIN/FN-related Chemotherapy Disturbance by EP2006 Prophylaxis Type: Patient Level |
7.5; 15.0 | — |
| PRIMARY Incidence of CIN/FN-related Hospitalization Outcomes by EP2006 Practice Patterns (Relative to Guidelines): Patient Level |
12.0; 16.8; 6.4; 5.2; 8.0; 2.1 | — |
| PRIMARY Incidence of CIN Grade 4 Episodes by EP2006 Dose: Patient Level |
11.3; 15.9 | — |
| PRIMARY Incidence of Outcomes by Mean GIS: Patient Level |
17.7; 17.5; 9.2; 26.9; 24.7; 18.9 | — |
| PRIMARY Incidence of Outcomes: Cycles Level |
3.9; 1.4; 1.5; 2.8; 6.7 | — |
| PRIMARY Incidence of Outcomes by Day of Study Drug Initiation: Cycle Level |
3.1; 2.8; 7.3; 1.0; 1.2; 2.1 | — |
| PRIMARY Incidence of Outcomes by Study Drug Duration: Cycle Level |
3.6; 3.9; 5.5; 1.2; 1.2; 2.2 | — |
| PRIMARY Number of Patients by Cause of Death |
61; 41; 14; 4; 2 | — |
| PRIMARY Number of Participants With All-cause Mortality by Any/no Grade 4 CIN and/or FN |
10; 46 | 0.5977 |
| PRIMARY Number of Participants With All-cause Mortality by CIN/FN-related Chemotherapy Disturbance |
3; 53 | 0.2435 |
| PRIMARY Number of Participants With Cancer-related Mortality by Any/no Grade 4 CIN or FN |
6; 29 | 0.7630 |
| PRIMARY Number of Participants With Cancer-related Mortality by Any CIN/FN-related Chemotherapy Disturbance |
2; 33 | 0.3830 |
| PRIMARY Number of Participants With Any CIN/FN-related Chemotherapy Disturbance by Prophylaxis Type |
78; 60 | 0.0002 sig |
| PRIMARY Number of Participants With Any CIN/FN-related Chemotherapy Disturbance by Treatment Decision |
37; 72; 29 | 0.0301 sig |
| PRIMARY Predictors of Absolute Neutrophil Count |
1185 | 0.0683 |
| PRIMARY Patient/Center-level Covariance Parameter Estimates of Absolute Neutrophil Count |
1185 | 0.0003 sig |
| PRIMARY EP2006 Day of Initiation: Cycle Distribution |
795; 1818; 793; 541; 270; 404 | — |
| PRIMARY EP2006 Cycles by Treatment Duration |
211; 339; 729; 422; 2718; 385 | — |
| PRIMARY Incidence of Outcomes |
13.2; 5.9; 6.1; 9.5; 22.3 | — |
| SECONDARY Cohort Identification |
1192; 43; 212 | — |
| SECONDARY Characteristics of Clusters: Hemoglobin Study Start |
12.35; 11.82 | — |
| SECONDARY Characteristics of Clusters: ECOG Performance Status |
0.75; 0.87 | — |
| SECONDARY Characteristics of Clusters: Cancer Stage |
511; 12; 681; 29 | — |
| SECONDARY Characteristics of Clusters: History of Antibiotic Use for CIN |
1190; 17; 2; 24 | — |
| SECONDARY Characteristics of Clusters: Liver, Renal and/or Cardiovascular Disease |
931; 19; 261; 22 | — |
| SECONDARY Modeling Grade 4 CIN Episode: Cycle Level |
294 | 0.003 sig |
| SECONDARY Modeling Grade 4 CIN Episode: Patient Level |
191 | 0.001 sig |
| SECONDARY Modeling FN Episode: Cycle Level |
105 | <0.001 sig |
| SECONDARY Modeling FN Episode: Patient Level |
86 | 0.003 sig |
| SECONDARY Modeling CIN/FN-related Hospitalization: Cycle Level |
111 | <0.001 sig |
| SECONDARY Modeling CIN/FN-related Hospitalization: Patient Level |
88 | <0.001 sig |
| SECONDARY Modeling CIN/FN-related Chemotherapy Disturbance: Cycle Level |
174 | <0.001 sig |
| SECONDARY Modeling CIN/FN-related Chemotherapy Disturbance: Patient Level (Patient-level Predictors) |
138 | 0.006 sig |
| SECONDARY Modeling Composite Outcome (Any of CIN Grade 4, FN, CIN/FN-related Hospitalization, CIN/FN-related Chemotherapy Disturbance): Cycle Level |
507 | 0.002 sig |
| SECONDARY Modeling Composite Outcome (Any of CIN Grade 4, FN, CIN/FN-related Hospitalization, CIN/FN-related Chemotherapy Disturbance): Patient Level |
323 | 0.006 sig |
| SECONDARY Patient-level Predictors for All-cause Mortality |
1272 | 0.0116 sig |
| SECONDARY Patient-level Predictor for Cancer-related Mortality |
1385 | <0.0001 sig |
Summary
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.
Eligibility 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.
Data sourced from ClinicalTrials.gov (NCT01459653). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.