Efficacy and safety of lipegfilgrastim versus pegfilgrastim: a randomized, multicenter, active-control phase 3 trial in patients with breast cancer receiving doxorubicin/docetaxel chemotherapy

Abstract

BackgroundLipegfilgrastim is a novel glyco-pegylated granulocyte-colony stimulating factor in development for neutropenia prophylaxis in cancer patients receiving chemotherapy. This phase III, double-blind, randomized, active-controlled, noninferiority trial compared the efficacy and safety of lipegfilgrastim versus pegfilgrastim in chemotherapy-naïve breast cancer patients receiving doxorubicin/docetaxel chemotherapy.MethodsPatients with high-risk stage II, III, or IV breast cancer and an absolute neutrophil count ≥1.5 × 109 cells/L were randomized to a single 6-mg subcutaneous injection of lipegfilgrastim (n = 101) or pegfilgrastim (n = 101) on day 2 of each 21-day chemotherapy cycle (4 cycles maximum). The primary efficacy endpoint was the duration of severe neutropenia during cycle 1.ResultsCycle 1: The mean duration of severe neutropenia for the lipegfilgrastim and pegfilgrastim groups was 0.7 and 0.8 days, respectively (λ = −0.218 [95% confidence interval: –0.498%, 0.062%], p = 0.126), and no severe neutropenia was observed in 56% and 49% of patients in the lipegfilgrastim and pegfilgrastim groups, respectively. All cycles: In the efficacy population, febrile neutropenia occurred in three pegfilgrastim-treated patients (all in cycle 1) and zero lipegfilgrastim-treated patients. Drug-related adverse events in the safety population were reported in 28% and 26% of patients i006E the lipegfilgrastim and pegfilgrastim groups, respectively.ConclusionThis study demonstrates that lipegfilgrastim 6 mg is as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy.Trial RegistrationEudra EEACTA200901599910The study protocol, two global amendments (Nos. 1 and 2), informed consent documents, and other appropriate study-related documents were reviewed and approved by the Ministry of Health of Ukraine Central Ethics Committee and local independent ethics committees (IECs).

AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2016

“…In a comparative effectiveness study, pegfilgrastim prophylaxis was associated with a reduced risk of neutrope niarelated or allcause hospitalization relative to filgrastim prophylaxis [37]. A recent study in highrisk breast cancer demonstrated that 6 mg lipegfilgrastim, a novel glycope gylated GCSF, was as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelo suppressive chemotherapy (1b B AGO+) [38]. Concerning prophylaxis of delayed chemotherapyinduced emesis, dexa methasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis in breast cancer patients treated with anthracycline plus cyclo phosphamide chemotherapy and receiving the same anti emetic prophylaxis for acute emesis (1b A AGO++) [39].…”

AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2018

“…In a comparative effectiveness study, pegfilgrastim prophylaxis was associated with a reduced risk of neutrope nia related or all cause hospitalization relative to filgrastim prophylaxis [37]. A recent study in high risk breast cancer demonstrated that 6 mg lipegfilgrastim, a novel glyco pe gylated G CSF, was as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelo suppressive chemotherapy (1b B AGO+) [38]. Concerning prophylaxis of delayed chemotherapy induced emesis, dexa methasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis in breast cancer patients treated with anthracycline plus cyclo phosphamide chemotherapy and receiving the same anti emetic prophylaxis for acute emesis (1b A AGO++) [39].…”

Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia

“…In Phase III trials in breast cancer patients, the safety of lipegfilgrastim was similar to pegfilgrastim. 34,35 The most commonly reported adverse events in both treatment groups were alopecia, nausea, asthenia, bone pain, diarrhea, fatigue, anorexia, vomiting, headache, and myalgia.…”

“…34 Breast cancer patients receiving chemotherapy were randomized 1:1 to receive either the 6.0-mg lipegfilgrastim dose (n=101) or 6.0-mg pegfilgrastim dose (n=101). Lipegfilgrastim was found to be noninferior to pegfilgrastim in the duration of severe neutropenia following cycle 1 of chemotherapy, with a 95% confidence interval of −0.498%, 0.062% days (P=0.1260).…”