A randomized, multi-center, open-label, phase II study of once-per-cycle DA-3031, a biosimilar pegylated G-CSF, compared with daily filgrastim in patients receiving TAC chemotherapy for early-stage breast cancer

Abstract

Fixed doses of 3.6 mg or 6 mg DA-3031 have an efficacy comparable to that of daily injections of filgrastim in ameliorating grade 4 neutropenia in patients receiving TAC chemotherapy.

Safety Profile of Biosimilar Filgrastim (Zarzio/Zarxio): A Combined Analysis of Phase III Studies

“…Comparing efficacy results for biosimilar filgrastim with efficacy results for reference filgrastim showed similar findings for the primary endpoint for the two groups included in our combined analysis (mean ± SD DSN for cycle 1: combined biosimilar, 1.04 ± 1.51; reference: 1.20 ± 1.02; cycles 1–4: combined biosimilar, 2.2 ± 2.91; reference: 3.4 ± 3.11). These values were generally in line with other randomized controlled studies with reference filgrastim (1.3–2.5 days) . There were no clinically meaningful differences between the combined biosimilar and reference groups for secondary endpoints, including infections and hospitalizations.…”

“…Indeed, bone pain was the most frequent AE in our combined analysis and was reported at a higher incidence in the reference group (15%), compared with the combined biosimilar group (5.8%). However, these levels are lower than reports from several other randomized controlled studies of patients with breast cancer receiving reference filgrastim (26%–42%) . Studies of patients with breast cancer receiving other G‐CSF products (lipegfilgrastim and pegfilgrastim) have reported incidences of bone pain of 10%–38% .…”

An open-label, randomized, multicenter dose-finding study of once-per-cycle pegfilgrastim versus daily filgrastim in Chinese breast cancer patients receiving TAC chemotherapy

“…TAC has become an established adjuvant treatment for both node-positive and node-negative early breast cancer due to its high efficacy [1][2][3][4][5][6][7][8][9][10][11]. However, TAC regimen is associated with marked hematologic and non-hematologic toxic effects resulted in higher incidence of neutropenia or related complications [23][24][25][26][27][28][29]. The study conducted by Holmes et al [24] demonstrated that a single subcutaneous injection of pegfilgrastim 100 lg/kg/cycle provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles for breast cancer patients receiving doxorubicin and docetaxel chemotherapy in enrolled centers in Europe, Australia and the USA.…”

“…This finding suggested that a single dose of pegfilgrastim (100 lg/kg/cycle) was as safe and effective as daily injections of filgrastim for neutrophil support in patients receiving PC, AC, PA and CHOP chemotherapy treatment, but unfortunately, this study did not enroll the patients with TAC regimen. In the same year, Parket al [29] published the paper about their phase II study conducted in Korean breast cancer patients who received TAC chemotherapy and found that fixed doses of 3.6 or 6 mg/cycle pegfilgrastim have similar efficacy to daily injections of 100 lg/m 2 filgrastim. A potential problem regarding the fixed dose is that it might not offer heavier patients complete clinical benefit due to a decreased overall per-kilogram dose.…”

“…Although many clinical trials have been performed to examine the efficacy and safety of pegfilgrastim in various clinical scenarios [23][24][25][26][27][28][29], there is still a short of evidencebased dose recommendations in Chinese breast cancer patients with TAC chemotherapy. This dose-finding study was designed to find an optimal fixed dose of pegfilgrastim via investigating the efficacy and safety at three dose levels in comparison with daily filgrastim in Chinese patients with early-stage breast cancer who are receiving TAC chemotherapy.…”