Abstract
Introduction
Febrile neutropenia (FN), a major risk factor for morbidity/mortality, is associated with dose delays and/or reductions in potentially cytotoxic chemotherapy (CT) regimens. It is defined as an oral temperature >38.5°C, or two consecutive readings of >38.0°C for 2 h, with an absolute neutrophil count <0.5 x 109/L, or expected to fall below 0.5 x 109/L. Guidelines from the European Organisation for Research and Treatment of Cancer (EORTC) recommend prophylactic use of granulocyte-colony stimulating factor (G-CSF) when using a CT regimen associated with a >20% risk of FN or in less intensive CT regimens if certain risk factors (eg >65 years, advanced disease, history of prior FN) are present. Biosimilar filgrastim (Nivestim™, Hospira Inc.) is a G-CSF licensed for the treatment of neutropenia and FN induced by myelosuppressive CT. As the NEXT (Nivestim™ safety profile in patiEnts treated with cytotoXic chemotherapy in real-life clinical pracTice) study was conducted in France, the real-life usage of biosimilar filgrastim is compared with that recommended by current EORTC guidelines.
Methods
The NEXT study was a prospective, non-interventional, longitudinal, multicentre, national study. The primary objective was to evaluate the safety of biosimilar filgrastim by gathering adverse event (AE) data. Secondary objectives included the description of patients (pts) treated with, and patterns of use of, biosimilar filgrastim.
Adult pts undergoing cytotoxic CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as primary or secondary prophylaxis, or as curative treatment, were included. The subanalysis presented here included only pts receiving prophylactic biosimilar filgrastim. Data were recorded on case report forms and included pt characteristics (demographics, medical history, CT-related data), biosimilar filgrastim treatment-related data (indication, dose, route of administration, treatment initiation) and treatment-emergent AEs, including FN. Individual FN risk factors were analysed. Pts were monitored for 1–6 CT cycles at three visits: inclusion, a follow-up visit during treatment and the final visit following CT.
Results
Overall, 2102 pts were included in the study analysis and 2065 pts received prophylactic biosimilar filgrastim. At inclusion, 73.9% of pts had no prior FN. Of the pts included in this analysis, 19.4% received CT associated with a high risk of developing FN (intermediate risk: 55.6%; low risk: 25.0%). Of the pts receiving CT regimens associated with an intermediate risk of FN, 95.4% had ≥1 risk factor for FN and of those receiving a regimen associated with a low risk of FN, 96.5% had ≥1 FN risk factor (Table 1).
Of all pts receiving prophylactic biosimilar filgrastim, 3.5% developed FN after the first CT cycle, 1.8% developed an infection and 2.4% were hospitalised for FN and/or infection after the first CT cycle. Median time to initiation of biosimilar filgrastim was 2 days after the last CT dose; mean treatment duration ± SD was 6.0±3.8 days. Anti-infective prophylaxis was reported in 14.5% of pts.
Conclusion
The majority of pts received prophylactic biosimilar filgrastim according to EORTC guidelines (ie either had >20% risk of FN or had ≥1 FN risk factor). Biosimilar filgrastim (Nivestim™) is an alternative therapeutic option for pts with prophylactic CT-induced neutropenia.
Proportion of patients with risk factors for FN
| Risk factor | Patients (%) | ||
|---|---|---|---|
| Chemotherapy regimen associated with a high risk (>20%) of FN | Chemotherapy regimen associated with an intermediate risk (10–20%) of FN | Chemotherapy regimen associated with a low risk (<10%) of FN | |
| Female | 51.5 | 58.6 | 47.9 |
| Age >65 years | 35.9 | 40.2 | 55.9 |
| Advanced disease | 40.4 | 41.9 | 66.4 |
| ≥1 severe comorbidity | 25.6 | 27.5 | 35.2 |
| Poor nutritional status* | 3.8 | 3.1 | 7.0 |
| WHO performance grade ≥3 | 0.0 | 0.1 | 0.3 |
| Haemoglobin <12 g/dL at inclusion | 37.7 | 39.1 | 50.9 |
| Concomitant radiotherapy | 2.3 | 2.8 | 5.0 |
| Prior FN | 7.6 | 6.1 | 11.5 |
| Risk factor | Patients (%) | ||
|---|---|---|---|
| Chemotherapy regimen associated with a high risk (>20%) of FN | Chemotherapy regimen associated with an intermediate risk (10–20%) of FN | Chemotherapy regimen associated with a low risk (<10%) of FN | |
| Female | 51.5 | 58.6 | 47.9 |
| Age >65 years | 35.9 | 40.2 | 55.9 |
| Advanced disease | 40.4 | 41.9 | 66.4 |
| ≥1 severe comorbidity | 25.6 | 27.5 | 35.2 |
| Poor nutritional status* | 3.8 | 3.1 | 7.0 |
| WHO performance grade ≥3 | 0.0 | 0.1 | 0.3 |
| Haemoglobin <12 g/dL at inclusion | 37.7 | 39.1 | 50.9 |
| Concomitant radiotherapy | 2.3 | 2.8 | 5.0 |
| Prior FN | 7.6 | 6.1 | 11.5 |
*Defined as a body mass index <18.5 kg/m2
WHO, World Health Organization
Maloisel:Pfizer: Research Funding; Novartis: Research Funding; Hospira: Research Funding; Amgen: Research Funding. Albrand:Hospira: Employment.
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