Safety of Biosimilar Filgrastim in Patients Undergoing Neutropenia-Inducing Chemotherapy: The Next Study

Introduction

Febrile neutropenia (FN) is a frequent and potentially serious complication of cytotoxic chemotherapy (CT). 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. Biosimilar filgrastim (Nivestim^™, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF) approved in France for the treatment of neutropenia and FN resulting from myelosuppressive CT. Previous clinical trials have demonstrated that the efficacy and safety of biosimilar filgrastim are similar to the reference product (Neupogen^®, Amgen Inc). The NEXT (Nivestim^™ safety profile in patiEnts treated with cytotoXic chemotherapy in real-life clinical pracTice) study aimed to confirm the safety of biosimilar filgrastim in patients (pts) undergoing cytotoxic CT for malignancies.

Methods

The NEXT study was a prospective, non-interventional, longitudinal, multicentre study conducted in France. The primary objective was to evaluate the safety of biosimilar filgrastim by gathering adverse event (AE) data. Secondary objectives included the description of 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. 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. Pts were monitored for 1–6 CT cycles at three visits: baseline, follow-ups during treatment and the final visit following CT.

Results

Of 2114 pts enrolled in the study, 2102 pts were included in the study analysis (50.2% male). Baseline demographics included, mean age ± standard deviation (SD) was 63.5±12.7 years, 75.0% of pts had solid tumours and 25.0% had haematological malignancies (lymphoma: 19.3%; myeloma: 2.2%; acute leukaemia: 0.2%; chronic lymphocytic leukaemia: 3.1% other haematological malignancies: 0.1%). At baseline, 92.5% of pts had no prior FN; 34.4% had previous CT; 20.2% had received previous G-CSF therapy. The majority (98.2%) of pts received prophylactic biosimilar filgrastim (primary prophylaxis: 8.2%; secondary prophylaxis: 90.1%). Of the pts receiving prophylactic biosimilar filgrastim, 79.9% received a dose of 30 MIU and therapy was administered subcutaneously in 99.4% of these pts. In the prophylactic biosimilar filgrastim group, the 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 these pts.

During the study 20.4% of pts experienced ≥1 AE; AEs were reported most frequently in pts with acute leukaemia (40.0%), lymphoma (21.6%) and solid tumours (21.1%). 12.7% of pts reported bone, muscular or chest pain. The other most common AEs included gastrointestinal disorders (5.5%), nausea (3.0%), general disorders and administration site disorders (2.4%), diarrhoea (2.3%) and headache (1.8%).

Of the 2114 pts enrolled, the incidence of FN was 4.9% (95% confidence interval [CI] 4.06, 5.98) and 3.1% (95% CI 2.39, 3.93) of pts experienced an infection. Mean duration of hospitalisation ± SD for FN and/or infection after the first CT cycle was 8.7±10.9 days. Overall, 4.7% of pts had ≥1 CT dose reduction and 7.4% of pts had a delay in administration of CT due to FN and/or infection.

Conclusion

These results provide further clinical evidence that biosimilar filgrastim (Nivestim^™) is safe and effective in treating and preventing neutropenia and febrile neutropenia in pts receiving cytotoxic CT for haematological malignancies and solid tumours. These data continue to support a similar clinical safety and efficacy profile of biosimilar filgrastim (Nivestim™) compared with the reference filgrastim (Neupogen^®, Amgen). Biosimilar filgrastim (Nivestim^™) is an alternative therapeutic option for pts with prophylactic or curative CT-induced neutropenia.