Introduction
Methods
Study design
Study selection
Parameter | Inclusion criteria | Exclusion criteria |
---|---|---|
Study type: Parts 1 and 2 | Published English-language studies including: • RCTs • NCTs • Observational studies (longitudinal studies, registry studies, open-label studies) • Systematic reviewsa
| Studies in animals but not humans Comments, editorials, letters, case reports, guidelines, health technology assessment reports, economic evaluations, narrative reviews, cancer registry reports, legal cases, debates, newspaper articles, opinions, research protocols, workshops, and patient education brochures |
Population: Parts 1 and 2 | Patients receiving filgrastim for one of its 6 US indications listed below: • Prophylaxis of CIN • Reducing time to neutrophil recovery and duration of fever in patients with AML receiving induction or consolidation chemotherapy • Reducing incidence and duration of sequelae of SN in patients with SCN • Mobilizing autologous hematopoietic progenitor cells in patients undergoing PBPC collection and therapy • Reducing duration of neutropenia and neutropenia-related clinical sequelae in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT • Increasing survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of ARS) No limits on age, gender, or geographic region | Patients receiving filgrastim outside of its six currently approved US indications Patients with existing FN receiving G-CSF treatment Studies in which the tumor type studied, if applicable, was not clear |
Interventions and comparators: Part 1 | Comparative studies of originator filgrastim (NEUPOGEN®) vs placebo, no treatment, or the following G-CSFs: • Granocyte (lenograstim) • Leridistim • Other short-acting G-CSFs • Neulasta® (pegfilgrastim) • Balugrastim (CG-10639, Neugranin™, albugranin) • Lipegfilgrastim (XM-22, Lonquex®) • Empegfilgrastim (Extimia®, BCD-017, metpegfilgrastim) • LAPS-G-CSF (SPI-2012, HM10460A) • Other long-acting G-CSF The above interventions (as either primary or secondary prophylaxis) were included | Studies specifying the use of filgrastim but not reporting filgrastim efficacy or safety data or outcomes of interest Studies in which filgrastim use was not prophylactic G-CSF-related outcomes not clear Studies in which the short-acting form of G-CSF was not specified to be filgrastim (NEUPOGEN®) Studies in which data for filgrastim were pooled with data for other short-acting G-CSFs Studies in which fewer than 50 patients received filgrastim for all other indications except SCN; in SCN studies with ≥ 10 patients were included |
Interventions and comparators: Part 2 | Comparative studies of originator filgrastim (NEUPOGEN®) vs placebo or no treatment | Data for any other short- or long-acting G-CSFs, including biosimilar filgrastims |
Outcomes: Parts 1 and 2 | Studies that reported neutropenia, ANC, neutropenia-related infection, or CD34+ cell mobilization and additional outcomes including: • Efficacy (data from RCTs and NCTs) and effectiveness (data from observational studies) that reported - Rate and duration of FN or grade 3 or 4 neutropenia - ANC nadir and white blood cell count - Survival - Rate and duration of hospitalization - Need for antibiotic prophylaxis or treatment - Chemotherapy dose reductions/delays, reduced dose intensity, and number of patients receiving full dose on schedule - CD34+ cell yield - Number of apheresis sessions required - Time to neutrophil and platelet recovery • Safety - AEs related to G-CSF, including bone pain, nausea/vomiting, diarrhea, leukocytosis, thrombocytopenia, allergic reactions, splenic rupture, acute respiratory distress syndrome, dyspnea, and alveolar hemorrhage and hemoptysis | Not applicable |
Data extraction and analysis
Statistical analysis
Results
Search results
Outcomes for filgrastim vs placebo or no treatment by indication
CIN
Author | Disease type | Filgrastim intervention and patient numbers | Incidence of grade 3 or 4 neutropenia |
P value |
---|---|---|---|---|
Randomized controlled trials | ||||
Crawford et al. [4] | SCLC |
N = 199 Filgrastim = 95 Placebo = 104 | Grade 4 neutropenia in cycle 1: 84 vs 98% |
P = 0.001 |
Papaldo et al. [20] | Breast cancer |
N = 503 Filgrastim = 254 No filgrastim = 249 | Grade 3/4 neutropenia: 28.6 vs 81.6% |
P < 0.00001 |
He et al. [19] | Breast cancer |
N = 107 PP filgrastim = 53 No PP filgrastim = 54 | Grade 3/4 neutropenia: 12.2 vs 52.3% |
P < 0.001 |
Zinzani et al. [25] | High-grade NHL |
N = 149 Filgrastim = 77 No filgrastim = 72 | Grade 4 neutropenia: 23.0 vs 55.5% |
P = 0.00005 |
Osby et al. [27] | NHL |
N = 455 Filgrastim = 226 No filgrastim = 229 | Granulocytopenia (< 0.5 × 109/L): CHOP arms 55 vs 89% CNOP arms 64 vs 86% | Not reported |
Nonrandomized clinical trial | ||||
Blayney et al. [30] | NSCLC and NHL | NSCLC (n = 33):a
Filgrastim = 24 No filgrastim = 9 NHL (n = 15):b
Filgrastim = 10 No filgrastim = 5 | Grade 3 and grade 4 neutropenia: 62 and 77% lower with filgrastim compared to control arm | Not reported |
Author | Disease type | Filgrastim intervention and patient numbers | Median duration of grade 3 or 4 neutropenia |
P value | Mean duration of severe neutropenia |
P value |
---|---|---|---|---|---|---|
Randomized controlled trials | ||||||
Crawford et al. [4] | SCLC |
N = 199 Filgrastim = 95 Placebo = 104 | Grade 4 neutropenia in cycle 1 (days): 3 vs 6 |
P < 0.001 | ||
Grade 4 neutropenia over 6 cycles (days): 1 vs 6 |
P < 0.001 | |||||
Trillet-Lenoir et al. [23] | SCLC |
N = 129 Filgrastim = 65 Placebo = 64 | Neutropenia (ANC < 1 × 109/L) over 6 cycles (days): 6 vs 15 | |||
Del Giglio et al. [21] | Breast cancer |
N = 348 Filgrastim = 136 XM02 = 140 Placebo/XM02 = 72 | Severe neutropenia (days): cycle 1 1.1 vs 1.1 vs 3.8 cycle 4 0.7 vs 0.7 vs 0.6 | NR | ||
Larson et al. [28] | ALL |
N = 198 Filgrastim = 102 Placebo = 96 | Median (IQR) Neutropenia (ANC < 1000/μL) (days): | |||
Course I 13 (10–16) vs 20 (15–27) |
P < 0.001 | |||||
Course IIA 5 (0–12) vs 13 (6–18) |
P < 0.001 | |||||
Course IIB 11 (4–17) vs 14 (10–25) |
P = 0.001 | |||||
Nonrandomized clinical trial | ||||||
Blayney et al. [30] | NSCLC and NHL | NSCLC (n = 33):a
Filgrastim = 24 No filgrastim = 9 NHL (n = 15):b
Filgrastim = 10 No filgrastim = 5 | Median duration of grade 3 and grade 4 neutropenia: 81 and 94% lower compared to control arm |