scholarly journals Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim: a phase III, randomised, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy

2018 ◽  
Vol 29 (1) ◽  
pp. 244-249 ◽  
Author(s):  
K. Blackwell ◽  
P. Gascon ◽  
A. Krendyukov ◽  
S. Gattu ◽  
Y. Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Study ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Double Blind ◽  
Myelosuppressive Chemotherapy ◽  
Safety And Efficacy

Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim for the prevention of severe neutropenia, in patients with breast cancer receiving myelosuppressive chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10116-10116 ◽  
Author(s):  
Andriy Krendyukov ◽  
Nadia Harbeck ◽  
Pedro Gascon ◽  
Sreekanth Gattu ◽  
Yuhan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reference Group ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Double Blind ◽  
Myelosuppressive Chemotherapy ◽  
The Us ◽  
Baseline Characteristics ◽  
Biosimilar Filgrastim ◽  
Clinical Trial Information

10116 Background: In 2015, filgrastim EP2006 (Zarxio) became the first biosimilar approved by the FDA for commercial use in the US. This phase III randomized, double-blind registration study in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy (TAC) compares US-licensed filgrastim, Neupogen (reference), with two groups who received alternating treatment with reference and biosimilar every other treatment cycle. Methods: A total of 218 patients receiving 5µg/kg/day filgrastim over 6 chemotherapy cycles were randomized 1:1:1:1 into 4 arms. Two arms received only 1 product, biosimilar or reference (unswitched), and 2 arms (switched) received alternating treatments every other cycle (biosimilar then reference or vice versa over cycles 1─6). Since the switch occurred from Cycle 2 onwards, this analysis compared pooled switched groups to the unswitched reference group for efficacy during Cycles 2─6. Safety was also assessed. Non-inferiority in febrile neutropenia (FN) rates between groups for Cycles 2─6 was shown if 95% confidence intervals (CIs) were within a pre-defined margin of -15%. Results: A total of107 patients switched treatment, and 51 patients received reference in all cycles. Baseline characteristics were similar between groups. Incidence of FN was 3.4% (switched) vs. 0% (reference) (95% CI: -9.65; 4.96), which is within the predefined non-inferiority margins. Infections occurred in 9.3% (switched) vs. 9.9% (reference). Hospitalization due to FN was low with 1 patient in Cycle 6 (switched). TEAEs related to filgrastim were reported in 42.1% (switched) vs. 39.2% (reference) (all cycles). Musculoskeletal/connective tissue disorders related to filgrastim occurred in 35.5% (switched) vs. 39.2% (reference) (all cycles), including bone pain (30.8% vs. 33.3%). No anti-drug antibodies were identified. Conclusions: There was no evidence of clinically meaningful differences when patients with breast cancer were switched from reference to biosimilar filgrastim, or from biosimilar to reference filgrastim. Clinical trial information: NCT01519700.

Efficacy and safety of balugrastim in chemotherapy-induced neutropenia: Integrated analysis of two randomized phase III studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17572-e17572
Author(s):  
Oleg Gladkov ◽  
Constantin D. Volovat ◽  
Steven Barash ◽  
Anton Buchner ◽  
Noa Avisar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Medical Condition ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Integrated Analysis ◽  
Efficacy And Safety ◽  
Breast Cancer Patients ◽  
Myelosuppressive Chemotherapy ◽  
Phase Iii Studies

e17572 Background: Balugrastim is a recombinant fusion protein composed of human serum albumin and human granulocyte colony-stimulating factor, which allows for once-per-chemotherapy cycle administration. We present a combined analysis of two double-blind, randomized Phase III studies comparing efficacy and safety of balugrastim vs pegfilgrastim in breast cancer patients receiving myelosuppressive chemotherapy (CTx). Methods: All patients were treated with doxorubicin 60 mg/m2 followed by docetaxel 75 mg/m2 administered by i.v. infusion on Day 1 of a 21-day cycle for up to 4 cycles. For each cycle, patients received a single s.c. injection of balugrastim approximately 24 hours after administration of CTx. The primary endpoint for both studies was duration of severe neutropenia (DSN) in Cycle 1. Safety of balugrastim was assessed by evaluating the type, frequency, and severity of adverse events (AEs); changes in laboratory parameters and vital signs, and immunogenicity over time. Analyses were performed in the per-protocol population. Results: A total of 469 patients were randomized to receive balugrastim 40 mg (N=235) or pegfilgrastim 6 mg (N=234). Mean DSN in Cycle 1 was 1.1±1.11 days in patients receiving balugrastim (n=236) and 1.0±1.14 days in patients receiving pegfilgrastim (n=234). Non-inferiority was demonstrated by statistical analysis for balugrastim vs pegfilgrastim for reduction in DSN across studies. Patients treated with balugrastim had a significantly shorter time to ANC recovery in Cycle 1 vs pegfilgrastim (2.0 vs 2.3 days; P=0.015). No other significant differences were seen between treatment groups in either study for any other secondary endpoints in Cycles 1–4. The safety profile was similar for both drugs, with the incidence of AEs consistent with the underlying medical condition and administration of myelosuppressive CTx. Conclusions: In both Phase III studies, non-inferiority was clearly demonstrated for balugrastim 40 mg vs pegfilgrastim 6 mg. Balugrastim is a safe and effective alternative to long-acting pegfilgrastim for reducing DSN in breast cancer patients receiving myelosuppressive chemotherapy. Clinical trial information: 2010-019001-42.

First and Subsequent Cycle Use of Pegfilgrastim Prevents Febrile Neutropenia in Patients With Breast Cancer: A Multicenter, Double-Blind, Placebo-Controlled Phase III Study

2005 ◽  
Vol 23 (6) ◽  
pp. 1178-1184 ◽  
Author(s):  
Charles L. Vogel ◽  
Marek Z. Wojtukiewicz ◽  
Robert R. Carroll ◽  
Sergei A. Tjulandin ◽  
Luis Javier Barajas-Figueroa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Febrile Neutropenia ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Open Label ◽  
Double Blind ◽  
Myelosuppressive Chemotherapy ◽  
Subsequent Cycle ◽  
Phase Iii Study ◽  
Chemotherapy Dose

Purpose We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients. Patients and Methods Patients were randomly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m2 docetaxel. The primary end point was the percentage of patients developing febrile neutropenia (defined as body temperature ≥ 38.2°C and neutrophil count < 0.5 × 109/L on the same day of the fever or the day after). Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia, intravenous (IV) anti-infectives required for febrile neutropenia, and the ability to maintain planned chemotherapy dose on time. Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles. Results Nine hundred twenty-eight patients received placebo (n = 465) or pegfilgrastim (n = 463). Patients receiving pegfilgrastim, compared with patients receiving placebo, had a lower incidence of febrile neutropenia (1% v 17%, respectively; P < .001), febrile neutropenia–related hospitalization (1% v 14%, respectively; P < .001), and use of IV anti-infectives (2% v 10%, respectively; P < .001). The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo (80% and 78%, respectively), as would be expected of the study design. Pegfilgrastim was generally well tolerated and safe, and the adverse events reported were typical of this patient population. Conclusion First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia, febrile neutropenia–related hospitalizations, and IV anti-infective use.

Safety profile of EP2006 biosimilar filgrastim: A combined analysis of two independent phase III studies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21701-e21701
Author(s):  
Nadia Harbeck ◽  
Pedro Gascon ◽  
Andriy Krendyukov ◽  
Nadja Hoebel ◽  
Sreekanth Gattu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Safety Profile ◽  
Safety Data ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Similar Data ◽  
Open Label ◽  
Double Blind ◽  
Registration Trial ◽  
Biosimilar Filgrastim

e21701 Background: The biosimilar filgrastim Zarzio (EP2006) was approved in Europe in 2009 and in 2015 became the first biosimilar approved by the FDA for use in the USA, marketed as Zarxio. Two phase III registration studies were performed to confirm the efficacy and safety of biosimilar filgrastim in women with breast cancer receiving myelotoxic chemotherapy. Methods: Data were combined from the studies to evaluate safety. Study 1 (US registration trial) was a randomized, double-blind comparative study of biosimilar and reference filgrastim (Neupogen, Amgen) in women ≥18 years with breast cancer receiving (neo)adjuvant treatment for 6 consecutive cycles with TAC (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2). Study 2 (EU registration trial) was a single-arm, open-label study of biosimilar filgrastim in women ≥18 years with breast cancer receiving doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 for 4 consecutive cycles. In/exclusion criteria and statistical definitions used for both studies were similar. Data of the patients treated with biosimilar filgrastim only were combined for Cycles 1-4. Results: A total of 277 patients (mean±SD age: 51.1±10.8 years) received biosimilar filgrastim (5 μg/kg bw/day sc). Treatment-emergent adverse events (TEAEs) were consistent with the known safety profile of filgrastim. The most frequently reported filgrastim-related TEAEs were musculoskeletal/connective tissue disorders (9.4%), including bone pain (5.8%) (Cycle 1). No neutralizing anti-filgrastim antibodies were detected. Mean±SD duration of severe neutropenia was 1.04±1.51 days in Cycle 1. Mean±SD depth of absolute neutrophil count nadir in Cycle 1 was 0.94±1.40 x 109/L. Conclusions: Safety data for biosimilar filgrastim EP2006 is consistent with reference filgrastim in women with breast cancer undergoing myelotoxic chemotherapy. Clinical trial information: NCT01519700. [Table: see text]

AMEERA-5: A randomized, double-blind phase III study of amcenestrant (SAR439859) + palbociclib versus letrozole + palbociclib for previously untreated ER+/HER2- advanced breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS1104-TPS1104
Author(s):  
Aditya Bardia ◽  
Javier Cortes ◽  
Sara A. Hurvitz ◽  
Suzette Delaloge ◽  
Hiroji Iwata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Phase I ◽  
Advanced Breast Cancer ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Phase Iii ◽  
Double Blind ◽  
Free Survival ◽  
Phase Iii Study

TPS1104 Background: Selective estrogen receptor degraders (SERDs) block estrogen receptor (ER) associated signaling and have created interest for treating patients (pts) with advanced ER+ breast cancer (BC). Fulvestrant is currently the only SERD available for advanced BC but requires intramuscular administration, limiting the applied dose, exposure and receptor engagement. Amcenestrant (SAR439859) is an oral SERD that binds with high affinity to both wild-type and mutant ER, blocking estradiol binding and promoting up to 98% ER degradation in preclinical studies. In the phase I AMEERA-1 study of pretreated pts with ER+/HER2- advanced BC, amcenestrant 150–600 mg once daily (QD) showed a mean ER occupancy of 94% with plasma concentrations > 100 ng/mL and a favorable safety profile (Bardia, 2019; data on file). Combination therapy with amcenestrant + palbociclib (palbo) was also evaluated as part of this ongoing phase I study. CDK 4/6 inhibitors (CDK4/6i) combined with an aromatase inhibitor (AI), the gold standard for first line treatment for advanced breast cancer, prolong progression free survival (PFS) in pts with no prior treatment for ER+/HER2- advanced BC, but OS benefit has not been shown yet in postmenopausal pts. There remains a clinical need for more effective treatments in this setting. Methods: AMEERA-5 (NCT04478266) is an ongoing, prospective, randomized, double-blind phase III study comparing the efficacy and safety of amcenestrant + palbo with that of letrozole + palbo in pts with advanced, locoregional recurrent or metastatic ER+/HER2- BC who have not received prior systemic therapy for advanced disease. The study includes men, pre/peri-menopausal (with goserelin) and post-menopausal women. Pts with progression during or within 12 months of (neo)adjuvant endocrine therapy using any of the following agents are excluded: AI, selective estrogen receptor modulators, CDK4/6i. Pts are randomized 1:1 to either continuous amcenestrant 200 mg or letrozole 2.5 mg QD orally with matching placebos; both combined with palbo 125 mg QD orally (d1–21 every 28-d cycle). Randomization is stratified according to disease type (de novo metastatic vs recurrent disease), the presence of visceral metastasis, and menopausal status. The primary endpoint is investigator assessed progression free survival (PFS) (RECIST v1.1). Secondary endpoints are overall survival, PFS2, objective response rate, duration of response, clinical benefit rate, pharmacokinetics of amcenestrant and palbo, health-related quality of life, time to chemotherapy, and safety. Biomarkers will be measured in paired tumor biopsies and cell free deoxyribonucleic acid (cfDNA) over time. Target enrolment = 1066 pts; enrolment as of 1/2021 = 33 pts. Bardia A, et al., J Clin Oncol. 2019; 37 (15 suppl):1054 Clinical trial information: NCT04478266 .

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