A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

Hegg, Roberto; Mattar, André; Matos-Neto, João Nunes de; Pedrini, José Luiz; Aleixo, Sabina B.; Rocha, Roberto Odebrecht; Cramer-Junior, Renato Peixoto; van-Eyll-Rocha, Sylvie

doi:10.6061/clinics/2016(10)06

Cited by 10 publications

(5 citation statements)

References 22 publications

(31 reference statements)

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“…Other retrospective studies as well as randomized trials examining the use of filgrastim and other short-acting G-CSFs for breast cancer patients receiving adjuvant or neoadjuvant chemotherapy reported incidences of FN in their cohorts ranging from 9.1% to 18% [ 15 - 17 ]. One study with similar findings to our own found FN incidence among Stage II to IV breast cancer patients treated with filgrastim (the majority receiving at least nine injections) to be 2.38% [ 18 ]. As such, the shorter course of low dose filgrastim administered among the medium weight cohort at least achieved similar rates of FN-related hospitalization (3.3%) reports that have been published for patients receiving the recommended dose.…”

Section: Discussionsupporting

confidence: 78%

Adequate Neutrophil Responses and Non-Inferior Clinical Outcomes Can Be Achieved by a Two-Day Course of Low-Dose Filgrastim: A Retrospective Single Institution Experience

Singh

Heisey

Elsayed

et al. 2017

Cureus

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Background Filgrastim is used in the setting of chemotherapy-induced neutropenia to stimulate recovery of bone marrow, which allows for further chemotherapy administration without delay. The recommended dose is 5 ug/kg. The commercially available vials of the drug come in two strengths; 300 ug and 480 ug. Due to these limitations in dosage formulations, it is a frequent occurrence to administer a lower dosage to patients weighing more than 60 kg, in whom the ideal dose would have been more than 300 ug but less than 480 ug. It is also a frequent practice to administer the drug for two consecutive days as it often leads to adequate response that will render patients eligible for their next cycle administration. Objective To determine whether a course of 300 ug of filgrastim administered daily for two consecutive days was as successful at reducing chemotherapy-induced neutropenia-related complications in patients with a higher weight (>60 kg) and hence receiving suboptimal dose as compared to those with weight less than 60 kg who are receiving the recommended dose. Methods We identified 91 patients from our facility with chemotherapy-induced neutropenia treated with 300 ug of filgrastim daily for two consecutive days, and we separated them into low, medium, and high weight groups. Multivariate logistic regression models examined correlations between outcomes (e.g., increases in absolute neutrophil count) and predictors (e.g., weight groups). Results The vast majority of encounters demonstrated rises in white blood cell (WBC) and absolute neutrophil count (ANC). Infection rates were not significantly different between low and medium weight groups (5% vs 0%; p = 0.1658), but the high weight group’s infection rate was significantly higher than the medium weight group (5% vs 33%; p = 0.001). The high weight group did have an increased rate of febrile neutropenia as compared to medium and low weight groups, but these differences were not significant. Incidences of chemotherapy delay and dose reduction were comparable across the three weight groups. Limitations Retrospective study, small sample size, heterogeneous cancer sites and different chemotherapy regimens administered limit generalizability of findings. Conclusion Patients with weights <85 kg receiving a two-day course of 300 ug of filgrastim have similar neutropenia-related complication rates with a potential percent cost-savings of roughly 43%.

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Section: Discussionsupporting

confidence: 78%

Adequate Neutrophil Responses and Non-Inferior Clinical Outcomes Can Be Achieved by a Two-Day Course of Low-Dose Filgrastim: A Retrospective Single Institution Experience

Singh

Heisey

Elsayed

et al. 2017

Cureus

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“…42 Phase II, OLSKBCII/ III410/41L-G-CSF Bio vs. Filgrastim6 mg/cycle vs.100 µg/m 2 /day32Hegg et al . 43 Phase III, OLBrazilBCII/ III/ IV2170/217S-G-CSF Bio vs. Filgrastim5 mg/m 2 /day vs.5 mg/m 2 /day33Blackwell et al . 44 Phase III, DBUSABCI/ II/ III/ IV3080/308L-G-CSF Bio vs. Pegfilgrastim6 mg/cycle vs. 6 mg/cycle34Harbeck et al .…”

Section: Resultsmentioning

confidence: 99%

Efficacy and tolerability of granulocyte colony-stimulating factors in cancer patients after chemotherapy: A systematic review and Bayesian network meta-analysis

Wang

Chen

Liu

et al. 2019

Sci Rep

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The optimum granulocyte colony-stimulating factor (G-CSF) treatment for cancer patients after being treated with cytotoxic chemotherapy remains unknown. Therefore, a systematic review and Bayesian network meta-analysis were performed to assess the efficacy and tolerability of 11 G-CSF drugs on patients after chemotherapy. A total of 73 randomized controlled trials (RCTs) containing 15,124 cancer patients were included for the final network meta-analysis. Compared with pegfilgrastim, there were a higher risk with filgrastim for incidence of febrile neutropenia (FN) (OR [95% CI]: 1.63 [1.07, 2.46]), and a higher risk with short-acting G-CSF (S-G-CSF) biosimilar and lenograstim for incidence of bone pain (BP) (OR [95% CI]: 6.45 [1.10, 65.73], 5.12 [1.14, 26.12], respectively). Mecapegfilgrastim, lipegfilgrastim and balugrastim were best G-CSF drugs in reducing FN (cumulative probabilities: 58%, 15%, 11%, respectively). S-G-CSF biosimilar, empegfilgrastim, and long-acting G-CSF (L-G-CSF) biosimilar were best G-CSF drugs in reducing severe neutropenia (SN) (cumulative probabilities: 21%, 20%, 15%, respectively). Mecapegfilgrastim, balugrastim, lipegfilgrastim and L-G-CSF biosimilar were best G-CSF drugs in reducing BP (cumulative probabilities: 20%, 14%, 8%, 8%, respectively). Mecapegfilgrastim, lipegfilgrastim and balugrastim might be the most appreciate G-CSF drugs with both good efficacy and tolerability when treating cancer patients after cytotoxic chemotherapy.

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“…However, to the best of our knowledge, this is the first clinical trial to evaluate a Peg-FilBS that was developed in this region. 17,18 The PegFilBS developed by GEMA BIOTECH S.A.U. is the first to be approved in Latin America for preventing febrile neutropenia in patients who are receiving myelosuppressive chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Biosimilar Versus Originator Pegfilgrastim for Preventing Chemotherapy-Induced Neutropenia: A Phase III Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study

Kowalyszyn

Fein

Richardet

et al. 2022

JCO Global Oncology

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PURPOSE This study evaluated the efficacy, safety, and immunogenicity of biosimilar pegfilgrastim (PegFilBS) and originator pegfilgrastim (PegFilOR) in patients with stage 2-4 breast cancer. METHODS This phase III randomized, multicenter, evaluator-blinded, noninferiority study recruited women with stage 2-4 breast cancer in Argentina who were scheduled to receive chemotherapy. Stratification was based on the breast cancer stage. The primary end point was the duration of severe neutropenia (DSN, noninferiority margin: 1 day) in the first chemotherapy cycle. Secondary end points assessed were incidence of severe neutropenia, grade 3 neutropenia, febrile neutropenia, infections, postchemotherapy hospitalization and duration, and the incidence of adverse drug reactions (ADRs). RESULTS A total of 120 patients were randomly assigned to receive PegFilBS (58 patients) or PegFilOR (62 patients). Severe neutropenia occurred in 52 of 283 cycles (18.4%) for 27 patients who received PegFilBS and in 48 of 297 cycles (16.2%) for 20 patients who received PegFilOR ( P = .48). During the first cycle, severe neutropenia occurred in 16 patients who received PegFilBS (DSN: 0.78 ± 1.53 days) and in 11 patients who received PegFilOR (DSN: 0.53 ± 1.25 days; 95% CI, –0.26 to 0.76 days). In the intention-to-treat analysis, the mean DSN values were 0.90 ± 1.79 days for the PegFilBS group and 0.50 ± 1.21 for the PegFilOR group (95% CI, –0.15 to 0.95 days). No significant differences were observed for the secondary efficacy end points. Three patients experienced seven ADRs in the PegFilBS group while 10 patients experienced 31 ADRs in the PegFilOR group. The most common ADR was myalgia. CONCLUSION Relative to PegFilOR, PegFilBS provided noninferior efficacy outcomes in Argentinian women with stage 2-4 breast cancer who were treated using myelosuppressive chemotherapy.

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A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

Cited by 10 publications

References 22 publications

Adequate Neutrophil Responses and Non-Inferior Clinical Outcomes Can Be Achieved by a Two-Day Course of Low-Dose Filgrastim: A Retrospective Single Institution Experience

Adequate Neutrophil Responses and Non-Inferior Clinical Outcomes Can Be Achieved by a Two-Day Course of Low-Dose Filgrastim: A Retrospective Single Institution Experience

Efficacy and tolerability of granulocyte colony-stimulating factors in cancer patients after chemotherapy: A systematic review and Bayesian network meta-analysis

Biosimilar Versus Originator Pegfilgrastim for Preventing Chemotherapy-Induced Neutropenia: A Phase III Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study

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