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British Journal of Clinical Pharmacology Jun 2024The recommended dosage of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) for Western chemotherapy patients is 6 mg per cycle. However,...
Low-dose pegylated recombinant human granulocyte-colony stimulating factor as hematopoietic support for adjuvant chemotherapy in Chinese patients with breast cancer: An open-label, randomized, non-inferiority trial.
AIMS
The recommended dosage of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) for Western chemotherapy patients is 6 mg per cycle. However, for Eastern Asians, the optimal dose remains unknown.
METHODS
This open-label, randomized, non-inferiority trial (NCT05283616) enrolled Chinese female breast cancer patients receiving adjuvant chemotherapy. Participants were randomized to receive either 3 or 6 mg of PEG-rhG-CSF per cycle, stratified by body weight (BW; ≤60 kg vs. >60 kg). The primary endpoint was timely absolute neutrophil count (ANC) recovery before the second cycle of chemotherapy.
RESULTS
A total of 122 patients were randomized and 116 were included for efficacy analyses. The timely ANC recovery rate in the 3 mg arm was 89.8%, compared to 93.0% in the 6 mg arm (one-sided 95% confidence interval [CI] lower limit for difference: -11.7%), meeting the prespecified non-inferiority margin of 15%. The rate was 93.3% with PEG-rhG-CSF 3 mg and 96.6% with 6 mg in patients with BW ≤ 60 kg, and 86.2% and 89.3%, respectively, in those with BW > 60 kg. Although the incidence of severe neutropenia was similar across arms, the occurrence of excessively high ANC and white blood cell counts was higher in the 6 mg arm. No grade ≥3 adverse events related to PEG-rhG-CSF occurred.
CONCLUSION
Three milligrams of PEG-rhG-CSF per cycle provided non-inferior neutrophil protection and attenuated neutrophil overshoot compared to 6 mg doses. This low-dose regimen could be a new supportive care option for Chinese breast cancer patients receiving anthracycline-based adjuvant chemotherapy.
PubMed: 38925586
DOI: 10.1111/bcp.16151 -
Cancer Treatment and Research... May 2024Myelosuppression, a challenge in cancer treatment, often results in severe complications. Prophylactic granulocyte colony-stimulating factors, particularly... (Review)
Review
INTRODUCTION
Myelosuppression, a challenge in cancer treatment, often results in severe complications. Prophylactic granulocyte colony-stimulating factors, particularly pegfilgrastim, mitigate chemotherapy-induced neutropenia. This narrative review evaluates the role of on-body injector (OBI) devices for pegfilgrastim administration. A comprehensive search strategy of PubMed and AI-powered intuitive search tools, complemented by authors' contributions, yielded a body of papers presenting evidence on OBI devices, their effectiveness and safety, the benefits and challenges of OBI versus pre-filled syringe administration, patient preferences for pegfilgrastim administration, and economic considerations.
DISCUSSION
OBI devices prove effective and safe, with advantages such as reduced clinic visits and enhanced adherence. Studies highlight cost-efficiency and expanded access, emphasizing the socioeconomic context. Patient and provider preferences underscore the potential of OBI devices in cancer care, with implications for healthcare resource utilization and pharmacoeconomics.
CONCLUSION
The value proposition of OBI devices lies in improving patient outcomes, convenience, resource optimization, and enhancing the overall cancer care experience. As biosimilar OBIs enter the market, they may offer cost savings, further influencing their adoption and their positioning as a cost-efficient alternative in cancer care. Ongoing research and technological advancements are expected to contribute to the broader acceptance of OBI devices in cancer care delivery.
PubMed: 38865836
DOI: 10.1016/j.ctarc.2024.100824 -
PloS One 2024To examine the cost-effectiveness of using granulocyte colony-stimulating factor (G-CSF) for primary or secondary prophylaxis in patients with breast cancer from the...
Cost-effectiveness analysis of granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced febrile neutropenia in patients with breast cancer in Taiwan.
OBJECTIVES
To examine the cost-effectiveness of using granulocyte colony-stimulating factor (G-CSF) for primary or secondary prophylaxis in patients with breast cancer from the perspective of Taiwan's National Health Insurance Administration.
METHODS
A Markov model was constructed to simulate the events that may occur during and after a high-risk chemotherapy treatment. Various G-CSF prophylaxis strategies and medications were compared in the model. Effectiveness data were derived from the literature and an analysis of the National Health Insurance Research Database (NHIRD). Cost data were obtained from a published NHIRD study, and health utility values were also obtained from the literature. Sensitivity analyses were performed to assess the uncertainty of the cost-effectiveness results.
RESULTS
In the base-case analysis, primary prophylaxis with pegfilgrastim had an incremental cost-effectiveness ratio (ICER) of NT$269,683 per quality-adjusted life year (QALY) gained compared to primary prophylaxis with lenograstim. The ICER for primary prophylaxis with lenograstim versus no G-CSF prophylaxis was NT$61,995 per QALY gained. The results were most sensitive to variations in relative risk of febrile neutropenia (FN) for pegfilgrastim versus no G-CSF prophylaxis. Furthermore, in the probabilistic sensitivity analysis, at a willingness-to-pay threshold of one times Taiwan's gross domestic product per capita, the probability of being cost-effective was 88.1% for primary prophylaxis with pegfilgrastim.
CONCLUSIONS
Our study suggests that primary prophylaxis with either short- or long-acting G-CSF could be considered cost-effective for FN prevention in breast cancer patients receiving high-risk regimens.
Topics: Humans; Breast Neoplasms; Cost-Benefit Analysis; Female; Taiwan; Granulocyte Colony-Stimulating Factor; Chemotherapy-Induced Febrile Neutropenia; Quality-Adjusted Life Years; Markov Chains; Filgrastim; Antineoplastic Agents; Cost-Effectiveness Analysis; Polyethylene Glycols
PubMed: 38857244
DOI: 10.1371/journal.pone.0303294 -
PloS One 2024To evaluate the impact of the entry of biosimilars on the pricing of eight biologic products in 57 countries and regions.
OBJECTIVE
To evaluate the impact of the entry of biosimilars on the pricing of eight biologic products in 57 countries and regions.
METHODS
We utilized an interrupted time series design and IQVIA MIDAS® data to analyze the annual sales data of eight biologic products (adalimumab, bevacizumab, epoetin, etanercept, filgrastim, infliximab, pegfilgrastim, and trastuzumab) across 57 countries and regions from January 1, 2012, to December 31, 2019. We examined the immediate and long-term changes in biologics ex-manufacturer pricing following the entry of biosimilars to the market.
RESULTS
Following the entry of biosimilars, the average price per dose of biologic product was immediately reduced by $438 for trastuzumab, $112 for infliximab, and $110 for bevacizumab. The persistent effect of biosimilars' market entry led to further reductions in price per dose every year: by $49 for adalimumab, $290 for filgrastim, $21 for infliximab, and $189 for trastuzumab. Similarly, we analyzed the impact of biosimilars on four biologics' prices in the US, where the prices of three biologics significantly decreased every year, with filgrastim, pegfilgrastim, and infliximab decreasing by $955, $753, and $104, respectively.
CONCLUSIONS
The introduction of biosimilars has significantly reduced the prices of biologics both globally and in the US. These findings not only demonstrate the economic benefits of increasing biosimilar utilization, but also emphasize the importance of biosimilars in controlling healthcare costs. Policies should aim to expand the availability of biosimilars to counteract the exponential growth of medical spending caused by the use of biologics.
Topics: Biosimilar Pharmaceuticals; Humans; Infliximab; Filgrastim; Biological Products; Drug Costs; Adalimumab; Etanercept; Trastuzumab; Costs and Cost Analysis; Polyethylene Glycols
PubMed: 38843282
DOI: 10.1371/journal.pone.0304851 -
Supportive Care in Cancer : Official... May 2024This study aims to delineate G-CSF treatment practices, assess decision criteria, and measure their implementation in ambulatory settings for patients with breast (BC),...
PURPOSE
This study aims to delineate G-CSF treatment practices, assess decision criteria, and measure their implementation in ambulatory settings for patients with breast (BC), lung (LC), or gastrointestinal cancers (GIC), beyond standard recommendations.
METHODS
In this non-interventional, cross-sectional, multicenter study, clinical cases were presented using conversational interfaces (chatbots), simulating a conversation with one or more virtual interlocutors through voice or text exchange. The clinical simulations were configured by four parameters: types of cancer, risk of FN related to chemotherapy and comorbidities, access to care, and therapy setting (adjuvant/neoadjuvant/metastatic).
RESULTS
The questionnaire was completed by 102 physicians. Most practitioners (84.5%) reported prescribing G-CSF, regardless of tumor type. G-CSF was prescribed more frequently for adjuvant/neoadjuvant therapy than for metastatic cases. The type of chemotherapy was cited as the first reason for prescribing G-CSF, with access to care being the second. Regarding the type of chemotherapy, physicians do not consider this factor alone, but combined with comorbidities and age (56.7% of cases). Pegfilgrastim long-acting was prescribed in most cases of BC and LC (70.1% and 86%, respectively), while filgrastim short-acting was named in the majority of cases of GIC (61.7%); 76.3% of physicians prescribed G-CSF as primary prophylaxis.
CONCLUSIONS
Our findings suggest that recommended practices are broadly followed. In the majority of cases, G-CSF is prescribed as primary prophylaxis. In addition, physicians seem more inclined to prescribe G-CSF to adjuvant/neoadjuvant patients rather than metastatic patients. Finally, the type of chemotherapy tends to be a more significant determining factor than the patient's background.
Topics: Humans; Cross-Sectional Studies; Female; Granulocyte Colony-Stimulating Factor; Surveys and Questionnaires; Middle Aged; Male; Practice Patterns, Physicians'; Adult; Aged; Lung Neoplasms; Breast Neoplasms; Ambulatory Care; Neoplasms; Outpatients
PubMed: 38743147
DOI: 10.1007/s00520-024-08524-0 -
Cureus Mar 2024Pegfilgrastim dramatically reduces febrile neutropenia (FN) caused by high-risk chemotherapy. This report details the presentation of a 72-year-old female who developed...
Pegfilgrastim dramatically reduces febrile neutropenia (FN) caused by high-risk chemotherapy. This report details the presentation of a 72-year-old female who developed a fatal infection of Pseudomonas aeruginosa pneumonia that occurred during preoperative chemotherapy despite pegfilgrastim administration. She was brought to the hospital with symptoms of high fever and general fatigue during chemotherapy, but her respiratory symptoms were minimal, and a chest computed tomography (CT) showed no obvious signs of pneumonia. She had FN. After she was hospitalized, her breathing and consciousness worsened rapidly, and the chest CT showed prominent lobar pneumonia. Her blood cultures suggested P. aeruginosa, so she was quickly switched to meropenem. She was diagnosed with septic shock and acute respiratory distress syndrome due to severe P. aeruginosa pneumonia, and she was started on noninvasive positive pressure ventilation with immunoglobulin preparations. P. aeruginosa developed drug resistance, so it was necessary to change antibiotics. She was discharged without complications of pulmonary fibrosis on chest CT. It is crucial to always be aware that severe infections can occur even with pegfilgrastim administration, promptly identify the causative pathogen, and intervene with early treatment.
PubMed: 38686264
DOI: 10.7759/cureus.57156 -
Analytical Methods : Advancing Methods... May 2024Determination of PEGylated proteins' intact mass by mass spectrometry is challenging due to the molecules' large size, excessive charges, and instrument limitations....
Determination of PEGylated proteins' intact mass by mass spectrometry is challenging due to the molecules' large size, excessive charges, and instrument limitations. Previous efforts have been reported. However, signal variability, ion coalescence, and a generally low degree of robustness have been observed. In this work, we have explored the capabilities of post-column infusion of dimethyl sulfoxide (DMSO) following reversed-phase liquid chromatography-mass spectrometry (RP-LCMS) to determine PEG-filgrastim' intact mass, and to characterize its PEG moiety. The method was optimized around reproducibility (six preparations, and three injection replicates) with an in-house prepared PEG-filgrastim standard. The method showed a mass accuracy of ≤1.2 Da. The average molecular weight (MW) was 40 147.9 Da. The number average molecular weight () and the weight average molecular weight () were observed to be 40 101.1 and 40 113.9 Da, respectively, both with an RSD of 0.03%. The molecular weight distribution of ethylene oxide (EO), the polydispersity index (PDI), was 1.0003 for all preparations with a minimum and maximum number of EO units of 448 ± 2 and 516 ± 2, respectively. The method was finally applied to commercially available Neulasta® lots where the and were 39 995.8 and 40 008.8 Da, respectively, both with an RSD of 0.1%. The minimum and maximum EO units across the lots were observed to be 444.5 ± 1.5 and 514 ± 3, respectively. The PDI for all Neulasta® lots was 1.0003. This study provides an insightful characterization of Neulasta® and describes a robust LC-MS methodology for the characterization of the PEGylated proteins.
Topics: Dimethyl Sulfoxide; Polyethylene Glycols; Molecular Weight; Mass Spectrometry; Chromatography, Reverse-Phase; Proteins; Reproducibility of Results; Gases
PubMed: 38685882
DOI: 10.1039/d4ay00660g -
Supportive Care in Cancer : Official... Apr 2024To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery,...
PURPOSE
To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival.
METHODS
Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72 h) or delayed administration (after 72 h) of HiDAC.
RESULTS
The difference in neutrophil recovery time was similar between the early and delayed groups (18 days versus 19 days, p < 0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p = 0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p = 0.28) as well as a trend towards longer median survival (16 months versus 19 months, p = 0.69) and overall survival (21 months versus 31 months, p = 0.47).
CONCLUSION
A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed administration of pegfilgrastim in these patients.
Topics: Humans; Cytarabine; Consolidation Chemotherapy; Retrospective Studies; Leukemia, Myeloid, Acute; Antineoplastic Combined Chemotherapy Protocols; Filgrastim; Polyethylene Glycols
PubMed: 38589646
DOI: 10.1007/s00520-024-08480-9 -
JAMA Health Forum Mar 2024Biologic drugs account for a growing share of US pharmaceutical spending. Competition from follow-on biosimilar products (subsequent versions that have no clinically...
IMPORTANCE
Biologic drugs account for a growing share of US pharmaceutical spending. Competition from follow-on biosimilar products (subsequent versions that have no clinically meaningful differences from the original biologic) has led to modest reductions in US health care spending, but these savings may not translate to lower out-of-pocket (OOP) costs for patients.
OBJECTIVE
To investigate whether biosimilar competition is associated with lower OOP spending for patients using biologics.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used a national commercial claims database (Optum Clinformatics Data Mart) to identify outpatient claims for 1 of 7 clinician-administered biologics (filgrastim, infliximab, pegfilgrastim, epoetin alfa, bevacizumab, rituximab, and trastuzumab) from January 2009 through March 2022. Claims by commercially insured patients younger than 65 years were included.
EXPOSURE
Year relative to first biosimilar availability and use of original or biosimilar version.
MAIN OUTCOMES AND MEASURES
Patients' annual OOP spending on biologics for each calendar year was determined, and OOP spending per claim between reference biologic and biosimilar versions was compared. Two-part regression models assessed for differences in OOP spending, adjusting for patient and clinical characteristics (age, sex, US Census region, health plan type, diagnosis, and place of service) and year relative to initial biosimilar entry.
RESULTS
Over 1.7 million claims from 190 364 individuals (median [IQR] age, 53 [42-59] years; 58.3% females) who used at least 1 of the 7 biologics between 2009 and 2022 were included in the analysis. Over 251 566 patient-years of observation, annual OOP costs increased before and after biosimilar availability. Two years after the start of biosimilar competition, the adjusted odds ratio of nonzero annual OOP spending was 1.08 (95% CI, 1.04-1.12; P < .001) and average nonzero annual spending was 12% higher (95% CI, 10%-14%; P < .001) compared with the year before biosimilar competition. After biosimilars became available, claims for biosimilars were more likely than reference biologics to have nonzero OOP costs (adjusted odds ratio, 1.13 [95% CI, 1.11-1.16]; P < .001) but had 8% lower mean nonzero OOP costs (adjusted mean ratio, 0.92 [95% CI, 0.90-0.93; P < .001). Findings varied by drug.
CONCLUSIONS AND RELEVANCE
Findings of this cohort study suggest that biosimilar competition was not consistently associated with lower OOP costs for commercially insured outpatients, highlighting the need for targeted policy interventions to ensure that the savings generated from biosimilar competition translate into increased affordability for patients who need biologics.
Topics: Female; Humans; Middle Aged; Male; Biosimilar Pharmaceuticals; Health Expenditures; Cohort Studies; Costs and Cost Analysis; Pharmacy; Biological Factors
PubMed: 38551589
DOI: 10.1001/jamahealthforum.2023.5429