scholarly journals A Phase III, Randomized, Multi-Center, Open-Label, Fixed Dose, Neulasta Active-Controlled Clinical Trial of F-627, a Novel G-CSF, in Women with Breast Cancer Receiving Myelotoxic Chemotherapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4290-4290
Author(s):  
John Glaspy ◽  
William Daley ◽  
Igor Bondarenko ◽  
Dean Rutty ◽  
Jianmin Chen
Keyword(s):  
Breast Cancer ◽  
Study Drug ◽  
Phase Iii ◽  
Chemotherapy Cycle ◽  
Severe Neutropenia ◽  
Fixed Dose ◽  
Controlled Study ◽  
Open Label ◽  
Treatment Groups ◽  
The Mean

Abstract Background - Chemotherapy-induced neutropenia (CIN) is the primary dose-limiting toxicity in patients receiving myelotoxic chemotherapy which is associated with increased morbidity and early mortality. Ryzneuta TM (F-627), a recombinant fusion protein containing human granulocyte-colony stimulating factor (G-CSF) and IgG2-Fc fragment, is intended to reduce CIN by utilizing the neutrophilic proliferating and activating properties of G-CSF. F-627 was designed as a novel, non-pegylated molecule with dimeric G-CSF, which may possess stronger G-CSF receptor activating properties and improved efficacy compared to filgrastim and pegfilgrastim. The primary objective of this study was to evaluate the safety and efficacy of F-627 given as a single fixed dose (20 mg) pre-filled syringe (PFS) as compared to Neulasta® (6 mg) in the first chemotherapy cycle. Methods - This was a phase III, multi-center, randomized, open-label, two-arm, active-controlled study that randomized female patients with Stage I to III invasive breast cancer who received 4 cycles of myelotoxic taxane + cyclophosphamide chemotherapy treatment. Forty-one (41) sites across 5 countries participated in the trial, including Bulgaria, Hungary, Russia, Ukraine, and US. Patients were randomized to F-627 or Neulasta® in a 1:1 ratio on the day of chemotherapy and administered study drug 24 hours after chemotherapy administration in each cycle. A total of 393 patients were randomized and analyzed for efficacy and safety. Clinical assessments were cycle-specific and included physical examination, serum samples for immunogenicity before each chemotherapy cycle, laboratory assessments, hematology and CBC with differentials, urinalysis, body weight, vital signs, adverse event (AE) collection, and concomitant medications. The pharmacokinetics (PK) and the pharmacodynamics (PD) of F-627 were also assessed. The primary efficacy endpoint was the duration in days of Grade 4 (severe) neutropenia (ANC <0.5 × 10 9/L) during cycle 1 of chemotherapy. Results - The mean duration of Grade 4 neutropenia in chemotherapy cycle 1 was 0.2 days for both F-627 and Neulasta®. F-627 was non-inferior compared to Neulasta® for the duration of Grade 4 neutropenia in chemotherapy cycle 1 with a mean difference of 0.0 days (95% CI: -0.1, 0.1), utilizing a non-inferiority margin of 0.6 days. The incidence of Grade 4 neutropenia in chemotherapy cycle 1 was comparable between F-627 and Neulasta®, 11.7% for both treatment groups. For chemotherapy cycles 2, 3, and 4, the incidence and duration of Grade 4 neutropenia was generally lower than in chemotherapy cycle 1. The mean durations of Grade 4 neutropenia were 0.1, 0.0, and 0.0 days for F-627 and 0.1, 0.1, and 0.1 days for Neulasta® in chemotherapy cycles 2,3,4, respectively. The incidence of Grade 4 neutropenia was 4.6%, 2.6%, and 1.6% for F-627 and 5.1%, 6.3%, and 5.3% for Neulasta® in chemotherapy cycles 2, 3, and 4, respectively. Across all chemotherapy cycles and for each chemotherapy cycle, the mean duration and the incidence of IV antibiotic use and hospitalization due to febrile neutropenia or any infection were low and comparable between F-627 and Neulasta®. The depth of ANC nadir was comparable in each chemotherapy cycle between F-627 and Neulasta®. For each chemotherapy cycle, time to ANC nadir was slightly longer for patients treated with F-627 than those with Neulasta®; the mean time to ANC nadir was 6.4, 6.1, 6.2, and 6.2 days for F-627, compared to 6.1,5.3, 5.7, and 5.5 days for Neulasta® in cycles 1, 2, 3, and 4, respectively. F-627 was well tolerated, with a low incidence of serious AEs and AEs leading to discontinuation, comparable to the profile for Neulasta®. There were 3 deaths during the study (1 for F-627 and 2 for Neulasta®). None of the deaths were related to study drug treatment. Clinical laboratory abnormalities were observed to be similar between the two treatment groups. Conclusion - Once-per-cycle F-627, given as a fixed 20 mg dose, was non-inferior to Neulasta® in reducing the duration of severe neutropenia following TC chemotherapy. F-627 was well tolerated during the study with an overall safety profile comparable to that for Neulasta®. F-627 is a safe, effective, and easy to use alternative to current CIN therapy. Disclosures Daley: Evive: Current Employment, Current holder of stock options in a privately-held company. Chen: Evive: Current Employment.

Eflapegrastim, a novel and potent long-acting GCSF for reducing chemotherapy-induced neutropenia: Integrated results from two phase III trials in breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 539-539
Author(s):  
Lee S. Schwartzberg ◽  
Gajanan Bhat ◽  
Jayaram S. Bharadwaj ◽  
Osama Hlalah ◽  
Alvaro Restrepo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Reduction ◽  
Early Stage ◽  
Absolute Risk ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Fixed Dose ◽  
Breast Cancer Patients ◽  
Open Label ◽  
Long Acting

539 Background: Eflapegrastim (E) is a novel long-acting GCSF comprised of recombinant human GCSF covalently linked to human IgG4 Fc fragment via a PEG linker (MW, 72 kDa). E showed increased potency vs pegfilgrastim (P) in preclinical and Phase I and II trials. Two identically designed Phase III pivotal trials (NCT02643420, NCT02953340) were conducted globally with a fixed dose of 13.2 mg E containing 3.6 mg GCSF to evaluate E vs P (6 mg) in pts receiving chemotherapy for early-stage breast cancer. Methods: Each open-label trial randomized pts 1:1 to a single subcutaneous dose of E 13.2 mg/0.6 mL or P 6 mg/0.6 mL on Day 2 of each of four 21-day cycles following Day 1 adj/neoadj docetaxel 75 mg/m2 + cyclophosphamide 600mg/m2 (TC). The primary endpoint was to demonstrate E non-inferiority (NI) to P as measured by mean duration of severe neutropenia (DSN) in Cycle 1. Results: A total 643 intent-to-treat pts (314 E/329 P) with median age 60 yrs (24–88) were enrolled. Cycle 1 mean (SD) DSN was 0.24 (0.581) vs 0.36 (0.789) days for E and P, confirming NI (p < .0001) and suggesting statistical superiority (p < .029). DSN NI was also shown across cycles 2–4. Among subgroups, including elderly (≥65 yrs) and overweight ( > 75kg) pts, DSN was reduced for E vs P. In Cycle 1, E showed an absolute risk reduction for severe neutropenia of 6.5% vs P (27.1% relative risk reduction, p < .043). Neutropenic complications (hospitalization and/or anti-infective use) were 2.9% and 4.0% for E and P (p = ns). Incidence of FN was low for both E and P, 1.6% vs 1.8% in Cycle 1 and 3.2% vs 3.0% overall. ANC profiles showed sustained increased levels for E vs P in the recovery phase across all cycles. Safety profiles were similar for E and P, including primarily for expected hematologic AEs and for bone pain and other musculoskeletal pain. Conclusions: These integrated pivotal trial results confirm a similar safety profile and non-inferiority in reducing neutropenic risk for E at a lower GCSF dose vs P. The data also suggests the potential for increased potency of E to deliver improved clinical benefit, a possibility that warrants further clinical trials. Clinical trial information: NCT02643420, NCT02953340.

Eflapegrastim, a novel, long-acting GCSF for reducing chemotherapy-induced neutropenia: Integrated results from two phase III trials in breast cancer patients.

2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 61-61
Author(s):  
Lee S. Schwartzberg ◽  
Gajanan Bhat ◽  
Jayaram S. Bharadwaj ◽  
Osama Hlalah ◽  
Alvaro Restrepo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Reduction ◽  
Early Stage ◽  
Absolute Risk ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Fixed Dose ◽  
Breast Cancer Patients ◽  
Open Label ◽  
Long Acting

61 Background: Eflapegrastim (E) is a novel, long-acting GCSF comprised of recombinant human GCSF covalently linked to human IgG4 Fc fragment via a PEG linker (MW, 72 kDa). E showed increased potency vs pegfilgrastim (P) in preclinical and Phase I and II trials. Two identically designed Phase III pivotal trials (NCT02643420, NCT02953340) were conducted globally with a fixed dose of 13.2 mg E containing 3.6 mg GCSF to evaluate E vs P (6 mg) in pts receiving chemotherapy for early-stage breast cancer. Methods: Each open-label trial randomized pts 1:1 to a single subcutaneous dose of E 13.2 mg/0.6 mL or P 6 mg/0.6 mL on Day 2 of each of four 21-day cycles following Day 1 adj/neoadj docetaxel 75 mg/m2 + cyclophosphamide 600mg/m2 (TC) . The primary endpoint was to demonstrate E non-inferiority (NI) to P as measured by mean duration of severe neutropenia (DSN) in Cycle 1. Results: A total 643 intent-to-treat pts (314 E/329 P) with median age 60 yrs (24–88) were enrolled. Cycle 1 mean (SD) DSN was 0.24 (0.581) vs 0.36 (0.789) days for E and P, confirming NI (p<.0001) and suggesting statistical superiority (p<.029). DSN NI was also shown across cycles 2–4. Among subgroups, including elderly (≥65 yrs) and overweight (>75kg) pts, DSN was reduced for E vs P. In Cycle 1, E showed an absolute risk reduction for severe neutropenia of 6.5% vs P (27.1% relative risk reduction, p<.043). Neutropenic complications (hospitalization and/or anti-infective use) were 2.9% and 4.0% for E and P (p=ns) in Cycle 1. Incidence of FN was low for both E and P, 1.6% vs 1.8% in Cycle 1 and 3.2% vs 3.0% overall. ANC profiles showed sustained increased levels for E vs P in the recovery phase across all cycles. Safety profiles including events of special interest, irrespective of grade, were mostly similar for E and P. The most common ≥ Grade 3 adverse events were hematologic due to chemotherapy. Conclusions: These integrated pivotal trial results confirm a similar safety profile and non-inferiority in reducing neutropenic risk for E at a lower GCSF dose vs P. The data also suggests the potential for increased potency of E to deliver improved clinical benefit, a possibility that warrants further clinical trials. Clinical trial information: NCT02643420 and NCT02953340.

A Comparison of Proposed Biosimilar and Originator Filgrastim for the Prevention of Neutropenia in Patients with Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Phase III, Randomized, Double-Blind Trial (The PIONEER study)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5133-5133 ◽  
Author(s):  
Kimberly Blackwell ◽  
Vladimir Semiglazov ◽  
Pedro Gascon ◽  
Roumen Nakov ◽  
Stefan Kramer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Group ◽  
Adverse Events ◽  
Lower Limit ◽  
Study Drug ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Pioneer Study ◽  
The Mean

Abstract Introduction: Biosimilars are biologics which have demonstrated highly similar safety, potency and purity to an originator product. Several biosimilars of recombinant human filgrastim, based on the originator Neupogen®, have become available in Europe since 2008 and are now in clinical use for the prevention of chemotherapy-induced neutropenia and hematopoietic stem cell mobilization. Filgrastim biosimilars are presently being developed for the U.S. market. Study design: A randomized, double-blind, four-group, multi-center phase III non-inferiority trial was performed with breast cancer patients treated with myleosuppressive chemotherapy. The two filgrastim products – proposed biosimilar, EP2006 (“biosimilar”) vs. originator (U.S.-licensed Neupogen®) - were compared regarding efficacy and safety. Patients included: women ≥18 years with histologically-proven breast cancer eligible for neoadjuvant or adjuvant treatment with docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC regimen) given for 6 cycles. Other key inclusion criteria included: Eastern Cooperative Oncology Group performance status ≤2 and adequate bone marrow function. Eligible patients were randomized to 4 groups with 2 of these groups alternating between the biosimilar and the originator filgrastim at the end of each cycle: 1) EP: treatment with EP2006 in all cycles; 2) EPNEU: EP2006 in Cycle 1, alternating between Neupogen and EP2006 in the following cycles; 3) NEUEP: Neupogen in Cycle 1, alternating between EP2006 and Neupogen in the following cycles; 4) NEU: treatment with Neupogen in all cycles. Patients received either biosimilar or originator filgrastim subcutaneously (daily dose of 5 µg/kg body weight) starting on Day 2 of each chemotherapy cycle until the absolute neutrophil count (ANC) recovered to 10×109/L after nadir or up to 14 days. Total duration of the study was 25 weeks: 3 weeks screening, 18 weeks treatment (total 6 cycles, 3 weeks each) and a follow-up visit 4 weeks after the last study drug administration. Primary objective was to assess the efficacy of the biosimilar compared to the originator with respect to mean duration of severe neutropenia (DSN) following Cycle 1 chemotherapy. A one-sided 97.5% confidence interval (CI) for the difference in the mean DSN calculated using ANCOVA model with factors “treatment” and “kind of therapy” and covariates “baseline ANC” was to be considered non-inferior if lower limit of this CI lies entirely above non-inferiority margin of -1 day. All secondary efficacy endpoints and safety endpoints were analyzed descriptively by treatment group. The study was conducted between December 2011 and June 2013. Results: Enrolled were 258 patients in 27 centers, of which 218 patients were randomized to treatment. The baseline characteristics were balanced between different groups. The per-protocol set included 204 patients out of 218 randomized patients. The safety set included 214 patients who received at least one dose of study drug. On average each patient received treatment for 8-9 days per cycle. The mean DSN in Cycle 1 was 1.17±1.11 days (biosimilar) and 1.20±1.02 days (originator); the mean difference in DSN was 0.04 days (97.5% CI, lower limit -0.26 days). The pre-defined non-inferiority criteria were met and the biosimilar was considered non-inferior to the originator filgrastim. The incidence of febrile neutropenia over all 6 cycles chemotherapy was comparably low in all treatment groups (EP: 2/40, 5.0%, EPNEU: 5/45, 11.1%, NEUEP: 1/44, 2.3%, NEU: 0/46, 0.0%). There was no obvious difference in incidences of treatment emergent adverse events between the treatment arms. Twelve patients experienced serious adverse events (EP: 5/53, 9.4% patients; EPNEU: 4/54, 7.4%; NEUEP: 1/55, 1.8%; NEU: 2/52, 3.8%). None of them were study drug related, including one death (in the EP treatment group due to pulmonary embolism). No subjects developed anti-drug antibodies. Conclusion: This large clinical study showed that efficacy and safety of the biosimilar was comparable to the originator filgrastim in prevention of neutropenia in patients with breast cancer. Repeated switching between the biosimilar and the originator filgrastim did not impact efficacy, safety or immunogenicity. Acknowledgment: The authors acknowledge the other investigators of the PIONEER study and acknowledge Gabor Stiegler, Sandoz Biopharmaceuticals for the medical writing. Disclosures Blackwell: Sandoz Biopharmaceuticals: Consultancy. Semiglazov:Sandoz Biopharmaceuticals: Consultancy. Gascon:Sandoz Biopharmaceuticals: Consultancy. Nakov:Sandoz Biopharmaceuticals: Employment. Kramer:Sandoz Biopharmaceuticals: Employment. Schwebig:Sandoz Biopharmaceuticals: Employment. Harbeck:Sandoz Biopharmaceuticals: Consultancy.

Efficacy and safety of BCD-017, a novel pegylated filgrastim: Results of open-label controlled phase II study in patients with breast cancer receiving myelosuppressive chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20593-e20593 ◽  
Author(s):  
Olga V. Salafet ◽  
Tatiana V. Chernovskaya ◽  
Ludmila P. Sheveleva ◽  
Andrey V. Khorinko ◽  
Tatiana I. Prokopenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
Open Label ◽  
Group A ◽  
Phase Iii Study ◽  
Study Support ◽  
To Receive

e20593 Background: Pegfilgrastim (conjugate of filgrastim and 20 kDa polyethylene glycol (PEG) is approved for treatment of chemotherapy-associated neutropenia. BCD-017 (empegfilgrastim) is a covalent conjugate of filgrastim with 30 kDa PEG. Increased molecular weight of PEG molecule may provide additional benefits compared to pegfilgrastim. Methods: To compare efficacy and safety of filgrastim and BCD-017 at 3 mg and 6 mg doses an open-label, randomized, active-comparator, non-inferiority trial was conducted. 60 patients with histologically or cytologically confirmed breast cancer were randomly assigned to receive either subcutaneous (s.c.) injection of 3 mg BCD-017 (n=21), 6 mg BCD-017 (n = 20), or 5 mg/kg s.c. injections of filgrastim (n=19) administered daily until ANC ≥ 10x109 cells/L (maximum of 14 days) after chemotherapy (doxorubicin 60 mg/m2 and docetaxel 75 mg/m2) with stratification for weight and prior chemotherapy exposure. The primary efficacy endpoint was the incidence of severe neutropenia (ANC < 1.0x109 cells/L) during the first cycle of chemotherapy. Results: Incidence of severe neutropenia during the first chemotherapy cycle was 85,7%, 65,0% and 61,1% in BCD-017 3 mg, BCD-017 6 mg and filgrastim groups, respectively. Differences between BCD-017 groups and filgrastim group were not significant. Mean duration of grade 4 neutropenia in cycle 1 was 0,43, 0,40 and 0,33 days, accordingly (95% CI for difference between BCD-017 3 mg and filgrastim groups -0.22 to 0.41; 95% CI for difference between BCD-017 6 mg and filgrastim groups -0.25 to 0.38). Febrile neutropenia was observed only in BCD-017 3 mg and BCD-017 6 mg groups (one case in each group). A single administration of BCD-017 at the doses of 3 mg and 6 mg was as safe and well tolerated as standard daily filgrastim administration. There were no unexpected adverse events in all groups. Conclusions: The results of this study support comparable efficacy of single s.c. injection of 6 mg BCD-017 versus daily 5 mg/kg s.c. injections of filgrastim. Further phase III study of BCD-017 for treatment and prophylaxis of neutropenia in patients receiving chemotherapy is necessary. Clinical trial information: NCT01569087.

scholarly journals Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer

2009 ◽  
Vol 27 (7) ◽  
pp. 1047-1053 ◽  
Author(s):  
Stephanie L. Hines ◽  
Betty Anne Mincey ◽  
Jeff A. Sloan ◽  
Sachdev P. Thomas ◽  
Elaine Chottiner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Mineral Density ◽  
Double Blind ◽  
Treatment Groups ◽  
The Mean ◽  
Prevention Of Bone Loss ◽  
To Receive

Purpose Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. Patients and Methods Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. Results A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. Conclusion Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.

Bupropion in the tratment of sexual dysfunction in women diagnosed with breast cancer: An open-label, fixed dose study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6072-6072
Author(s):  
C. Mathias ◽  
E. Moraes ◽  
C. Bastos ◽  
R. Athanazio ◽  
G. Nunez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sexual Function ◽  
Hormonal Therapy ◽  
Sexual Experience ◽  
Female Breast Cancer ◽  
Open Trial ◽  
Fixed Dose ◽  
Breast Cancer Patients ◽  
Open Label ◽  
The Mean

6072 Background: Sexual morbidity after chemotherapy and hormonal therapy for breast cancer can seriously affect patients’ quality of life. Bupropion is an antidepressant that has been reported to increase libido. Objective: To investigate the improvement of sexual function in female breast cancer patients using bupropion. Methods: We performed an eight week open trial using bupropion in women diagnosed with breast cancer who had received chemotherapy and were currently receiving adjunctive hormonal therapy. The Arizona Sexual Experience Scale (ASEX) was used. The ASEX scale includes five questions that evaluate sexual function in the following areas: libido, excitability and ability to reach orgasm. Women received oral Bupropion 150mg/ daily for eight weeks and were evaluated prior to the initiation of the study and again during Weeks 4 and 8. Results: Twenty patients were included in the study. At the beginning of the study, the mean ASEX score was 23.45 [21.67–25.24] 95% CI. After four weeks of treatment, we observed a reduction in the mean ASEX score that persisted until the end of the study, at eight weeks: 18.45 [16.59–20.31] 95% CI, p = 0.0003) and 18.95 (SD ± 5.02 [16.60–21.30] 95% CI, p = 0.0024), respectively. Conclusions: In this non-controlled open trial bupropion 150 mg/daily was associated with improved sexual function in women receiving adjuvant systemic treatment for breast cancer. No significant financial relationships to disclose.

A Phase II, Randomized, Multi-Centre, Open-Label, Active-Controlled, Dose-Finding Trial of F-627 (benefilgrastim) in Women with Breast Cancer Receiving Myelotoxic Chemotherapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1584-1584 ◽  
Author(s):  
John Glaspy ◽  
Tom Tang ◽  
Dean Rutty ◽  
Xiaoqiang Yan ◽  
Igor Bondarenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Subcutaneous Injection ◽  
Chemotherapy Regimen ◽  
Chemotherapy Cycle ◽  
Severe Neutropenia ◽  
Fixed Dose ◽  
High Dose ◽  
Tac Chemotherapy ◽  
Grade 3

Abstract Neutropenia is common in patients receiving myelotoxic chemotherapy. Benefilgrastim, an rhG-CSF dimer (rhG-CSF-FC fusion protein), is a once-per-cycle therapy for prophylactic neutrophil support. In this Phase II trial, 230 women with stage I-IV breast cancer are to be treated for 4 chemotherapy cycles with either docetaxel/cyclophosphamide (TC) or doxorubicin/docetaxel/cyclophosphamide (TAC) chemotherapy, with each cycle lasting approximately 21 days. Patients will be randomized to receive either benefilgrastim or pegfilgrastim (Neulasta; 6 mg fixed dose) one day after chemotherapy during each cycle, as a subcutaneous injection. Dose levels of benefilgrastim examined are 80 µg/kg (TC patients only), and 240 and 320 µg/kg (TC and TAC patients). The primary endpoint is the duration of grade 3/4 neutropenia in chemotherapy cycle 1. As of August 1, 2014, 232 patients have completed chemotherapy cycle 1; safety and efficacy were analyzed for these enrolled patients. For the TC chemotherapy regimen, a total of 141 patients were randomized (ratio = 1:1:1:1) into 4 arms (80, 240, and 320 µg/kg benefilgrastim or 6 mg pegfilgrastim). In the TAC chemotherapy regimen, a total of 91 patients were randomized (ratio = 1:1:1) into 3 arms (240 and 320 µg/kg benefilgrastim or 6 mg pegfilgrastim). The incidence of grade 3/4 and grade 4 neutropenia and their mean durations in cycle 1 are provided in Table 1. There were higher incidences of grade 3/4 and grade 4 neutropenia in the TAC regimen compared to the TC regimen. The safety profiles of benefilgrastim and pegfilgrastim were similar. A total of 10 SAEs were reported in 6 patients with the majority (7 SAEs in 4 patients) occurring in those receiving pegfilgrastim. The most commonly observed treatment emergent adverse events (>10% of total TC + TAC patients) were: alopecia, nausea, asthenia, neutropenia, bone pain, and fatigue. The rates were similar amongst treatment regimens and treatment groups. In summary, a single subcutaneous injection of benefilgrastim 240 or 320 µg/kg provided neutrophil support to patients treated with both the TC and TAC chemotherapy regimens. The safety profile of benefilgrastim was comparable to that of pegfilgrastim during multiple chemotherapy cycles. The results suggest a potential use of benefilgrastim for the management of severe neutropenia in cancer patients undergoing high dose chemotherapy. Abstract 1584. Table 1: Preliminary Results TC Regimen TAC Regimen Benefilgrastim Pegfilgrastim 6 mg (N=35) Benefilgrastim Pegfilgrastim 6 mg (N=29) 80 µg/kg (N=35) 240 µg/kg (N=37) 320 µg/kg (N=34) 240 µg/kg (N=29) 320 µg/kg (N=30) Grade 3/4 neutropenia n/N (%) 10/35 (28.6) 10/37 (27.0) 7/34 (20.6) 7/35 (20.0) 17/25 (68.0) 19/26 (73.1) 17/24 (70.8) Duration (days) Mean (SD) 95% CI 2.4 (2.07) 1.2, 3.6 2.2 (0.79) 1.7, 2.7 1.9 (0.38) 1.6, 2.1 1.4 (0.79) 0.9, 2.0 2.8 (1.67) 2.1, 3.5 2.6 (1.07) 2.2, 3.1 2.2 (0.73) 1.9, 2.5 Grade 4 neutropenia n/N (%) 4/35 (11.4) 7/37 (18.9) 6/34 (17.6) 3/35 (8.6) 14/25 (56.0) 17/26 (65.4) 15/24 (62.5) Duration (days) Mean (SD) 95% CI 2.0 (1.15) 0.6, 3.4 2.1 (0.90) 1.5, 2.8 1.2 (0.41) 0.8, 1.5 1.0 (0.00) 1.0, 1.0 1.9 (1.33) 1.3, 2.6 2.0 (0.87) 1.6, 2.4 1.5 (0.64) 1.2, 1.8 SAEs n (%) # SAEs 0 0 1 (2.7) 1 0 0 2 (5.7) 3 0 0 1 (3.3) 2 2 (6.9) 4 CI=confidence interval; SAE=serious adverse event; SD=standard deviation Disclosures Glaspy: Generon (Shanghai) Corporation Ltd.: Research Funding. Tang:Generon (Shanghai) Corporation Ltd.: Employment. Rutty:Everest Clinical Research Services Inc.: Employment; Generon (Shanghai) Corporation Ltd.: Consultancy; Schering Corporation: Consultancy; Roche: Consultancy; Methylgene: Consultancy; Steba Biotech SA: Consultancy; Aderans Research Institute Inc: Consultancy; Stem Cell Theraputics: Consultancy; Genentech: Consultancy; Pearly Therapeutics: Consultancy; Sundise Chinese Medicine Technology Development Corp: Consultancy; Endocyte, Inc: Consultancy; Hutchison Medipharma: Consultancy; Nutrition Science Partners Limited: Consultancy. Yan:Generon (Shanghai) Corporation Ltd.: Employment.

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