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Cancer Research and Treatment Jul 2023We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared...
Eflapegrastim versus Pegfilgrastim for Chemotherapy-Induced Neutropenia in Korean and Asian Patients with Early Breast Cancer: Results from the Two Phase III ADVANCE and RECOVER Studies.
PURPOSE
We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials.
MATERIALS AND METHODS
Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations.
RESULTS
Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: -0.120 days (95% confidence interval [CI], -0.227 to -0.016), -0.288 (95% CI, -0.714 to 0.143), and -0.267 (95% CI, -0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations.
CONCLUSION
This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.
Topics: Female; Humans; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Filgrastim; Granulocyte Colony-Stimulating Factor; Neutropenia; Polyethylene Glycols; Republic of Korea; East Asian People
PubMed: 36701846
DOI: 10.4143/crt.2022.987 -
Advances in Therapy Nov 2023Pegfilgrastim-cbqv (UDENYCA; Coherus BioSciences, Redwood City, CA, USA) is a pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA, USA) biosimilar approved for... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Pegfilgrastim-cbqv (UDENYCA; Coherus BioSciences, Redwood City, CA, USA) is a pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA, USA) biosimilar approved for administration by prefilled syringe (PFS). The recently approved pegfilgrastim-cbqv prefilled autoinjector (AI) was developed as another method of self-administration and to aid in-office use, providing flexibility in drug delivery. The objectives of the study were to assess the pharmacokinetics (PK) and pharmacodynamics (PD) to determine bioequivalence of the prefilled AI and the PFS for administration of pegfilgrastim-cbqv and to assess the safety profile of the prefilled AI.
METHODS
During this open-label, two-period crossover study, healthy adult males (N = 155) were randomly assigned (1:1 ratio) to receive a subcutaneous injection of pegfilgrastim-cbqv using a prefilled AI (n = 76) or a PFS (n = 79) in period 1. During period 2, participants received an injection using the other method. Primary PK and secondary PD parameters were calculated to assess the bioequivalence of the treatment as administered by the two delivery methods. Safety and immunogenicity were also assessed.
RESULTS
The 90% CIs of the geometric mean ratios for the PK and PD parameters were within the required range (80-125%), demonstrating bioequivalence between the pegfilgrastim-cbqv prefilled AI and PFS. Treatment-emergent adverse events (TEAEs) were reported by 75% and 74.1% of participants in the prefilled AI and PFS groups, respectively. The most common TEAEs in both treatment groups were myalgia, bone pain, and headache. AI-device-related TEAEs were injection site pain (1.4%) and injection site bruising (0.7%). The incidence of antidrug antibodies and neutralizing antibodies was low and was similar in both treatment sequences.
CONCLUSIONS
The bioequivalence of pegfilgrastim-cbqv administered using a prefilled AI and a PFS was established. The safety, including immunogenicity profiles, of pegfilgrastim-cbqv administered using the prefilled AI and the PFS were similar, with no new safety findings.
Topics: Adult; Humans; Male; Therapeutic Equivalency; Syringes; Cross-Over Studies; Injections, Subcutaneous; Healthy Volunteers; Biosimilar Pharmaceuticals; Injection Site Reaction; Pain
PubMed: 37707674
DOI: 10.1007/s12325-023-02636-5 -
Cancer Medicine Oct 2023Pegfilgrastim is indicated to decrease the incidence of chemotherapy-induced febrile neutropenia. It is the first granulocyte-colony stimulating factor approved for...
INTRODUCTION
Pegfilgrastim is indicated to decrease the incidence of chemotherapy-induced febrile neutropenia. It is the first granulocyte-colony stimulating factor approved for prophylactic use regardless of carcinoma type and is marketed in Japan as G-LASTA (Kyowa Kirin Co., Ltd., Tokyo, Japan). MD-110 is a biosimilar of pegfilgrastim. This phase III, multicenter, open-label, single-arm study investigated the efficacy and safety of MD-110 in early-stage breast cancer patients receiving neoadjuvant or adjuvant myelosuppressive chemotherapy.
METHODS
A total of 101 patients received the study drug. Each patient received docetaxel 75 mg/m and cyclophosphamide 600 mg/m (TC) for four cycles on day 1 of each cycle. MD-110 (3.6 mg) was administered subcutaneously on day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 (days with absolute neutrophil count < 500/mm ). The safety endpoints were adverse events and the presence of antidrug antibodies.
RESULTS
The mean (SD) duration of severe neutropenia for MD-110 was 0.2 (0.4) days. The upper limit of the two-sided 95% confidence interval for the mean duration of severe neutropenia was 0.2 days, below the predefined threshold of 3.0 days. The incidence of febrile neutropenia, the secondary efficacy endpoint, was 6.9% (7/101). Adverse events, occurring in more than 50% of patients, were alopecia, constipation, and malaise, which are common side effects of TC chemotherapy. Antidrug antibodies were negative in all patients.
CONCLUSION
MD-110 was effective against chemotherapy-induced neutropenia. No additional safety concern, compared with the originator, was observed in patients with breast cancer receiving TC chemotherapy.(JapicCTI-205230).
Topics: Female; Humans; Antineoplastic Combined Chemotherapy Protocols; Biosimilar Pharmaceuticals; Breast Neoplasms; Filgrastim; Granulocyte Colony-Stimulating Factor; Neutropenia; Polyethylene Glycols
PubMed: 37824431
DOI: 10.1002/cam4.6519 -
Scientific Reports Feb 2024Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of...
Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of prophylactic pegfilgrastim on FN prevention, therapeutic efficacy, and prognosis after RD have not been fully evaluated in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred and eighty-eight patients with advanced NSCLC who received RD as second-line therapy after platinum-based chemotherapy plus PD-1 blockade were included. Patients were divided into groups with and without prophylactic pegfilgrastim, and adverse events, efficacy, and prognosis were compared between both groups. Of the 288 patients, 247 received prophylactic pegfilgrastim and 41 did not. The frequency of grade 3/4 neutropenia was 62 patients (25.1%) in the pegfilgrastim group and 28 (68.3%) in the control group (p < 0.001). The frequency of FN was 25 patients (10.1%) in the pegfilgrastim group and 10 (24.4%) in the control group (p = 0.018). The objective response rate was 31.2% and 14.6% in the pegfilgrastim and control groups (p = 0.039), respectively. The disease control rate was 72.9% in the pegfilgrastim group and 51.2% in the control group (p = 0.009). Median progression free survival was 4.3 months in the pegfilgrastim group and 2.5 months in the control group (p = 0.002). The median overall survival was 12.8 and 8.1 months in the pegfilgrastim and control groups (p = 0.004), respectively. Prophylactic pegfilgrastim for RD reduced the frequency of grade 3/4 neutropenia and febrile neutropenia and did not appear to be detrimental to patient outcome RD.Clinical Trial Registration Number: UMIN000042333.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Ramucirumab; Docetaxel; Lung Neoplasms; Polyethylene Glycols; Leukopenia; Febrile Neutropenia; Antineoplastic Combined Chemotherapy Protocols; Granulocyte Colony-Stimulating Factor; Filgrastim
PubMed: 38360906
DOI: 10.1038/s41598-024-54166-x -
Supportive Care in Cancer : Official... Sep 2023Clinical practice guidelines recommend the use of all approved granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, as primary...
PURPOSE
Clinical practice guidelines recommend the use of all approved granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, as primary febrile neutropenia (FN) prophylaxis in patients receiving high- or intermediate-risk regimens (in those with additional patient risk factors). Previous studies have examined G-CSF cost-effectiveness by cancer type in patients with a high baseline risk of FN. This study evaluated patients with breast cancer (BC), non-small cell lung cancer (NSCLC), or non-Hodgkin's lymphoma (NHL) receiving therapy who were at intermediate risk for FN and compared primary prophylaxis (PP) and secondary prophylaxis (SP) using biosimilar filgrastim or biosimilar pegfilgrastim in Austria, France, and Germany.
METHODS
A Markov cycle tree-based model was constructed to evaluate PP versus SP in patients with BC, NSCLC, or NHL receiving therapy over a lifetime horizon. Cost-effectiveness was evaluated over a range of willingness-to-pay (WTP) thresholds for incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analyses evaluated uncertainty.
RESULTS
Results demonstrated that using biosimilar filgrastim as PP compared to SP resulted in incremental cost-effectiveness ratios (ICERs) well below the most commonly accepted WTP threshold of €30,000. Across all three countries, PP in NSCLC had the lowest cost per QALY, and in France, PP was both cheaper and more effective than SP. Similar results were found using biosimilar pegfilgrastim, with ICERs generally higher than those for filgrastim.
CONCLUSIONS
Biosimilar filgrastim and pegfilgrastim as primary prophylaxis are cost-effective approaches to avoid FN events in patients with BC, NSCLC, or NHL at intermediate risk for FN in Austria, France, and Germany.
Topics: Humans; Female; Filgrastim; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Biosimilar Pharmaceuticals; Lung Neoplasms; Granulocyte Colony-Stimulating Factor; Breast Neoplasms; Lymphoma, Non-Hodgkin; Febrile Neutropenia; Granulocytes
PubMed: 37728795
DOI: 10.1007/s00520-023-08043-4 -
Drug Safety Dec 2023Biosimilars are additional treatment options that are approved based on robust analytical and clinical comparisons with their reference biologic. At the time of initial... (Review)
Review
Long-Term Real-World Post-approval Safety Data of Multiple Biosimilars from One Marketing-Authorization Holder After More than 18 Years Since Their First Biosimilar Launch.
BACKGROUND
Biosimilars are additional treatment options that are approved based on robust analytical and clinical comparisons with their reference biologic. At the time of initial approval, the full safety profile of a biosimilar is inferred from the reference biologic. Nonetheless, there are still lingering concerns related to the long-term safety of biosimilars. Therefore, we reviewed the post-approval pharmacovigilance data for eight marketed biosimilars from one Marketing Authorization Holder (MAH) to summarize their safety experience in a real-world setting for up to 18 years since their first biosimilar launch.
METHODS
Post-approval cumulative patient exposure and safety experience for eight Sandoz biosimilars [adalimumab (Hyrimoz), epoetin alfa (Binocrit), etanercept (Erelzi), filgrastim (Zarzio), infliximab (Zessly), pegfilgrastim (Ziextenzo), rituximab (Rixathon), and somatropin (Omnitrope)] was summarized based on the available pharmacovigilance data from Periodic Safety Update Reports (PSURs) and the corresponding health authority-authored PSUR assessment reports, where available, as of 31 January 2023. Exposure to all biosimilars was calculated in patient treatment days (PTD) except for rituximab, which was expressed in number of patient doses (PD).
RESULTS
The combined post-approval cumulative exposure to seven out of the eight marketed Sandoz biosimilars was more than 1.3 billion PTD and for rituximab more than 1.8 million PD. Overall, a critical analysis of the cumulative safety data of all eight Sandoz biosimilar PSURs concluded that the overall benefit-risk profile of each remains favorable and is consistent with the respective reference biologics.
CONCLUSIONS
This is one of the largest reviews of post-approval biosimilar pharmacovigilance data to date by one MAH. The real-world experience of all eight marketed Sandoz biosimilars for up to 18 years demonstrates that Sandoz biosimilars can be used as safely as their respective reference biologics. Therefore, patients and healthcare providers can be confident in the clinical benefit and safety of Sandoz biosimilars. It is reasonable to believe that similar conclusions about safety may be reached for other biosimilars developed and approved to the high standards as are already in place by major health authorities such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The long-term safety of biosimilars demonstrated here provides strong support for the concept of biosimilarity.
Topics: Humans; Biosimilar Pharmaceuticals; Rituximab; Infliximab; Adalimumab; Epoetin Alfa; Marketing; Drug Approval
PubMed: 37902937
DOI: 10.1007/s40264-023-01371-8 -
Thoracic Cancer Dec 2023Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia...
BACKGROUND
Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P-PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P-PEG as second-line chemotherapy for SCLC.
METHODS
We retrospectively reviewed patients with SCLC who received AMR as second-line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P-PEG in their regimen, patients (n = 60) were divided into P-PEG (n = 21) and non-P-PEG groups, and their clinical outcomes were evaluated.
RESULTS
Median of AMR treatment cycles was five (range: 1-39 cycles) in P-PEG group and four (range: 1-15 cycles) in non-P-PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P-PEG group than in the non-P-PEG group. The objective response rates were 52.4% and 30.8%, and median progression-free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P-PEG and non-P-PEG groups, respectively.
CONCLUSIONS
AMR with P-PEG as second-line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P-PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Retrospective Studies; Neoplasm Recurrence, Local; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37873674
DOI: 10.1111/1759-7714.15140