Short-acting Granulocyte Colony-stimulating Factors Research Articles

Outcome and Cost-Effectiveness Analysis of Long-acting G-CSF as Primary Prophylaxis of Neutropenia Induced by Chemotherapy in Breast Cancer Patients, From a Retrospective Study.

This retrospective analysis aimed to evaluate the clinical outcomes and cost-effectiveness of long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia caused by chemotherapy for breast cancer. Patients with breast cancer who received long- or short-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia were enrolled in this study, and incidences of neutropenia were compared between two groups. A decision-analytic and a Markov model were used to compare the health benefits and costs of utilizing long- vs short-acting granulocyte-colony stimulating factor as the primary prophylaxis from the perspective of the Chinese health service system. Subsequently, one-way deterministic and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratios were calculated in baseline and sensitivity analyses. Patients receiving long-acting granulocyte-colony stimulating factor as the primary prophylaxis of chemotherapy-induced neutropenia experienced a significant lower incidence of this adverse event, compared with the short-acting one for 2 to 7 days. The outcomes of baseline analysis indicated that long-acting granulocyte-colony stimulating factor had a gain of 0.08 quality-adjusted life years and costed $149 more than the short-acting one, yielding an incremental cost-effectiveness ratio of $1792 per quality-adjusted life year. The sensitivity analysis proved the stability of our models and economic efficiency of long-acting granulocyte-colony stimulating factor. Patients receiving long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia experienced lower risk of this event compared with those underusing short-acting one. The long-acting granulocyte-colony stimulating factor may be a more cost-effective strategy for primary prophylaxis of neutropenia than short-acting one, considering the Chinese willingness-to-pay threshold of $12158.6 per quality-adjusted life year.

Patterns of primary prophylactic granulocyte colony-stimulating factor use in older Medicare patients with cancer receiving myelosuppressive chemotherapy.

Guidelines recommend primary prophylactic (PP) granulocyte colony stimulating factor (G-CSF) for prevention of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy with high risk (HR: > 20%), or intermediate risk (IR:10-20%) of FN and ≥ 1 patient risk factor (e.g., age ≥ 65y). The current retrospective cohort study describes patterns of PP-G-CSF in older Medicare patients undergoing myelosuppressive chemotherapy with HR/IR of FN. Patients aged ≥ 66y initiating chemotherapy regimens with HR/IR of FN to treat breast, colorectal, lung, or ovarian cancer, or Non-Hodgkin's Lymphoma were selected using Medicare 20% sample (2013-2015) and 100% cancer patient (2014-2017) data. PP-G-CSF use was identified in the first cycle. Timing of pegfilgrastim pre-filled syringe (PFS) administration, proportion of patients completing all cycles (adherence) with pegfilgrastim PFS or on-body injector (OBI), and duration of short-acting G-CSF (sG-CSF) was described across all cycles. Of 64,893 patients receiving HR/IR for FN, 71% received HR and 29% IR regimens. Overall, PP-G-CSF use in the first cycle was 53% (HR: 74%; IR: 44%) and varied across cancers. Adherence with pegfilgrastim was slightly higher among OBI initiators (78%) than PFS (74%). Number of PP-sG-CSF administrations (mean [SD]) per cycle was 5.1 (SD: 2.7) overall, 5.4 (2.6) for HR, and 4.9 (2.7) for IR. Despite cancer treatment guidelines recommending PP-G-CSF use to reduce risk of FN associated with HR and IR (with ≥ 1 patient risk-factor) regimens, PP-G-CSF remains underutilized in older patients, across cancer types and regimens. Opportunities exist for improvement in use of PP-G-CSF.

Abstract OT2-21-01: A randomized, multicenter pragmatic trial comparing bone pain from a single dose of pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy (REaCT-5G)

Abstract Background: Current guidelines recommend the use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis to prevent febrile neutropenia (FN) associated with commonly used breast cancer chemotherapy regimens. Filgrastim (FIL) is a short-acting G-CSF injection that requires daily subcutaneous injection starting 24-72 hours after chemotherapy for 5 to 10 days. Pegfilgrastim (PEG) is a long-acting, pegylated formulation that requires a single injection 24-72 hours after chemotherapy. G-CSF causes bone pain in approximately 70% of patients, which can be severe in over 25% of cases. While registration trials for PEG showed bone pain from PEG was comparable to FIL when given for a median duration of 11 days, many oncologists are now only prescribing FIL for 5 days based on a multicenter RCT showing that 5 days of FIL is non-inferior to 7 or 10 days of FIL in terms of FN and treatment-related hospitalizations. Furthermore, the cost of 5 days of FIL ($CA 721.55 for 300 mcg dose) is half of the price of a single dose of PEG ($CA 1424.63). Therefore, if 5 days of FIL leads to significantly less bone pain, this may improve health-related quality of life (HR-QoL) for patients, improve adherence to G-CSF, and improve cost-effectiveness. Methods: Patients receiving neo-/adjuvant chemotherapy for early stage breast cancer requiring primary FN prophylaxis with G-CSF will be approached for this pragmatic, multicenter, open-label superiority RCT. Using the Rethinking Clinical Trials (REaCT) methodology that incorporates an integrated oral consent model, eligible and consented patients will be randomized to either 5 days of FIL or one day of PEG with each cycle of chemotherapy. The primary endpoint is bone pain during the first 5 days after G-CSF injection using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) of the Bone Pain Diary. Secondary endpoints include incidence of FN and treatment-related hospitalizations, incidence of chemotherapy delay, dose-reduction, or discontinuation, incidence of chemotherapy-related mortality, rate of G-CSF compliance, healthcare resource utilization, HR-QoL, and cost-effectiveness. Participants will also complete a Treatment Preference Questionnaire (TPQ) exploring the relative importance of different factors in deciding between PEG vs. 5 days of FIL both before randomization and at the end of the study. To achieve 80% power in an ANCOVA analysis and assuming 5% are loss to follow-up, the planned sample size is 232 patients (116 per arm). The randomization (1:1 ratio) will be stratified by treatment center (4 centers) and chemotherapy regimen (taxane-based vs. anthracycline-based in the first 4 cycles). Results: The study opened for enrollment on June 9, 2021. As of July 6, 2021, the study has opened at one site, and 13 patients have been randomized.Conclusion: This will be the first RCT using a patient-reported Bone Pain Diary that was co-developed by patient partners to measure bone pain between 5 days of FIL vs. PEG. In collaboration with patient partners, the study incorporates a tool (TPQ) that explores factors that may be important in deciding between PEG and FIL, with the aim of translating the findings of this study into real world clinical practice. Citation Format: Terry L. Ng, Monica Taljaard, Marie-France Savard, Carol Stober, Stuart Nicholls, Lisa Vandermeer, Kednapa Thavorn, Claudia Hampel, Jennifer Shamess, Natalie Mills, John F. Hilton, Mark Clemons. A randomized, multicenter pragmatic trial comparing bone pain from a single dose of pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy (REaCT-5G) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-21-01.

Analysis of the Safety of Pegfilgrastim Addition in Bleomycin, Etoposide, and Cisplatin Treatment Patients With Germ Cell Tumors.

It has been reported that chemotherapy drugs and granulocyte colony-stimulating factor (G-CSF) administered on the same day can aggravate neutropenia. In the present study, we investigated the safety of pegfilgrastim during bleomycin, etoposide, and cisplatin (BEP) therapy. This single-center retrospective study, including 137 cycles of BEP therapy for germ cell tumors between January 2008 and April 2021, investigated safety. Short-acting G-CSF was used for 84 cycles and pegfilgrastim was used for 53 cycles. In the pegfilgrastim group, neutrophil count at nadir was significantly higher than in the G-CSF group (median 1,650/μl and 680/μl, respectively). The incidence of grade 3–4 neutropenia was significantly higher and the duration longer in the G-CSF group. Also, there was no significant difference in the incidence of febrile neutropenia. In conclusion, concomitant use of pegfilgrastim during BEP therapy did not increase neutropenia and was effective in terms of safety.

The Role of Prophylactic Application of Granulocyte Colony Stimulating Factor in Adjuvant Chemotherapy for Epithelial Ovarian Cancer

The goal of this study was to investigate the relative merits of granulocyte colony stimulating factor (G-CSF) prophylaxis for patients with epithelial ovarian cancer (EOC). The Institutional Review Board of the Women's Hospital, Zhejiang University School of Medicine has approved this study (No. IRB-20200132-R) with a waiver of informed consent. Patients with EOC who received the combination of a platinum drug and paclitaxel (TP) chemotherapy regimens in the hospital from January 1, 2016, to November 30, 2020, were included in this retrospective cohort study. To assess clinical effectiveness, patients were categorized into groups who received either long-acting G-CSF or short-acting G-CSF prophylaxis with and without prophylaxis. The incidence of neutropenia and adverse events were compared between groups. All results of chemotherapy were pooled for analysis. Of the identified cases, 128 patients were evaluated. Long-acting G-CSF and short-acting G-CSF were applied in 51 and 41 patients, respectively. The absolute neutrophil count at the nadir was significantly lower in patients with G-CSF prophylaxis than those without G-CSF (p = 0.001). The duration of ANC levels < 2.0 x 109/L in cycles using short-acting G-CSF was longer than that in those receiving long-acting G-CSF (p = 0.045). There were no serious adverse events observed in patients with G-CSF. No significant differences in the incidence of febrile neutropenia (FN) and duration of grade 2 - 4 neutropenia were observed between groups receiving G-CSF prophylaxis and those without. Primary prophylaxis with G-CSF in chemotherapy for epithelial ovarian cancer appears to be of low value in terms of its relationship to the incidence of FN and prognosis.

Long-acting versus short-acting granulocyte colony-stimulating factors among cancer patients after chemotherapy in China: A systematic review and meta-analysis of randomized controlled trials.

Background:Granulocyte colony-stimulating factors (G-CSFs) include long-acting ones and short-acting ones. They have been mainly applied in Chinese clinical practice for years to prevent neutropenia. However, which type of G-CSF is more superior has not been conclusively determined.Methods:A systematic literature search was conducted using the PubMed, Embase, Cochrane Library, clinical trials.gov, China National Knowledge Infrastructure, and WAN FANG databases for related studies published till August 2021. Revman 5.3 software was used to assess the effectiveness and safety of these 2 types of G-CSFs in patients undergoing chemotherapy.Results:Ten studies involving 1916 patients were included in our meta-analysis to compare the effectiveness and safety of long-acting G-CSFs and short-acting G-CSFs. We found that the incidence of febrile neutropenia (relative risk [RR] 0.82; 95% confidence interval [CI] 0.57–1.17), the recovery time of the absolute neutrophil count (mean difference –0.23; 95% CI –0.49 to 0.03), and the fatigue rate (RR 0.82; 95% CI 0.62–1.07) were similar between the long- and the short-acting G-CSFs. However, the long-acting G-CSFs significantly decreased the incidence (RR 0.86; 95% CI 0.76–0.96) and shortened the duration (mean difference –0.19; 95% CI –0.38 to 0.00) of severe (grade ≥3) neutropenia, and decreased the rate of bone and/or muscle pain (RR 0.75; 95% CI 0.58–0.98).Conclusion:Primary prophylaxis with long-acting G-CSFs was more effective and safer than primary prophylaxis with short-acting G-CSFs in Chinese adults undergoing chemotherapy.

Real-world utilization and costs with biosimilar and reference filgrastim in patients with breast cancer receiving myelosuppressive chemotherapy in a community oncology setting from 2015 to 2017.

57 Background: Biosimilars have potential to reduce healthcare costs and increase access in the United States, but lack of uptake has contributed to lost savings. Filgrastim-sndz was the first FDA-approved biosimilar, and much can be learned by evaluating its uptake. In February 2016, the US Oncology Network converted to filgrastim-sndz as its short-acting granulocyte colony-stimulating factor (GCSF) of choice for prevention of febrile neutropenia (FN) following myelosuppressive chemotherapy (MCT). To understand utilization and cost patterns, this study analyzes real-world data of GCSFs within a community oncology network during the initial period of conversion to the first biosimilar available in the US. Methods: This descriptive retrospective observational study used electronic health record data for female breast cancer (BC) patients receiving GCSF and MCT at high risk of FN. Patient cohorts were defined by first receipt of either filgrastim or filgrastim-sndz during the 410 days before and after biosimilar conversion. Healthcare resource utilization (HCRU) and costs for GCSF and complete blood counts (CBC) were collected at GCSF initiation through the earliest of 30 days following end of MCT, loss to follow up, death, or data cutoff. Results: 146 patients were identified: 81 (55.5%) filgrastim and 65 (44.5%) filgrastim-sndz. No directional differences existed in baseline characteristics between the cohorts. Higher proportions of filgrastim-sndz patients received dose-dense MCT (33.8% vs 22.2%). Time trends show an initial spike in HCRU and cost for filgrastim-sndz patients after formulary conversion, which subsequently decreased and converged to that of the filgrastim cohort after 12 months. When aggregated, the overall median total administration counts, per patient per month (PPPM) and dosage, were marginally higher for filgrastim-sndz (5 vs 3; 2.9 vs 1.4; 1920 vs 1440 mcg, respectively). Median PPPM costs were higher for filgrastim-sndz ($803 vs $545). Median CBC utilization and costs were higher for filgrastim-sndz (2.8 vs 2.5; $28 vs $23, respectively). Conclusions: This study provides insight into real-world HCRU and cost patterns after formulary conversion to a biosimilar for BC patients receiving MCT and GCSF. As a descriptive study, causal inferences cannot be made and an underlying effect from index chemotherapy cannot be excluded. Convergence of HCRU and costs after 12 months suggests that overall results may be driven by behavior at initial formulary switch. Since filgrastim-sndz was the first US biosimilar approved, the uptake may be indicative of an experience with biosimilar acceptance in general. Future real-world studies of biosimilars must consider inconsistent utilization and practice trends during the time frame directly following formulary conversion.

Budget Impact Analysis of Switching Chemotherapy Patients Using Granulocyte Colony-Stimulating Factors (G-CSFs) from Pegfilgrastim to Short-Acting G-CSFs in the United States

Introduction: Neutropenia is a common complication in patients receiving myelosuppressive chemotherapy for nonmyeloid malignancies. Severe and febrile neutropenia (FN) are associated with prolonged hospitalization, serious infections and broad-spectrum antibiotic use, decreased quality of life, and increased medical costs and mortality. G-CSFs are often administered to reduce incidence, severity, and duration of FN in chemotherapy patients. While pegfilgrastim is dosed once per chemotherapy cycle (14-day efficacy), data suggest the average duration of short-acting G-CSF use is considerably shorter than 14 days. This analysis estimated the budget impact of increasing utilization of short-acting G-CSFs (filgrastim [Neupogen®], tbo-filgrastim [Granix®, a filgrastim follow-on biologic], and filgrastim-sndz [Zarxio®, a filgrastim biosimilar]) while decreasing utilization of long-acting pegfilgrastim (Neulasta®) products for patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy from a US payer perspective.Methods: An interactive budget impact model was developed to estimate changes in drug and administration costs associated with a projected 10% reduction in pegfilgrastim market share (an estimated 7.6% of the total G-CSF market) and an equal increase split evenly across short-acting product lines (approximately 1/3 allocated to 300-mcg products and 2/3 allocated to 480-mg products within product lines) for patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy within a 1-million-member health plan. Patient self-administration at home was assumed for 40% of patients receiving short-acting G-CSFs and 10% of patients receiving long-acting agents, with the remaining administered by health care provider (HCP) in an office or other outpatient setting. Patients receiving short-acting G-CSFs were assumed to require 10 doses per chemotherapy cycle, with long-acting agents given once per cycle. Self-administered products were purchased via the patient's pharmacy benefit at an assumed Tier 3 formulary status with a patient copay of $57 per prescription. HCP-administered products were assumed to be primarily (85%) purchased through the patient's medical benefit and provided on site, while a small proportion of patients (15%) were assumed to purchase G-CSFs through their pharmacy benefit to be HCP administered; in both cases, administration costs for injections were included, and with pharmacy benefit adjudication, a patient drug cost-share was applied ($57 per prescription). Base-case data were derived from publicly available resources. The budget impact was calculated using a 1-year time horizon, along with the difference in effective per-member per-year (PMPY) cost between current and proposed scenarios; univariate sensitivity analyses were conducted.Results: The effective annual per-patient plan drug costs ranged from $12,288 to $30,772 for short-acting G-CSFs and from $27,013 to $33,698 for pegfilgrastim (depending on dose and adjudication channel per product). The estimated total effective annual plan cost prior to the utilization shift was $425,518,352 (PMPY = $425.53) and was $419,985,093 (PMPY = $419.99) following the shift. The home administration budget increased by $5,793,056, while the HCP administration budget decreased by $11,326,314, for an overall annual cost savings of $5,533,259 (PMPY = $5.54). Per-patient savings for tbo-filgrastim and filgrastim-sndz ranged from 16.1% to 54.5%, depending on dose and adjudication channel. The model was most sensitive to changes in pegfilgrastim acquisition cost and the patient's medical benefit cost-share.Conclusions: Budget impact analyses examine the financial impact associated with the introduction of new treatments or shifting existing treatment patterns to help decision makers determine how best to allocate resources. Without considering additional impacts of health plan contracted rates and manufacturer rebates, the annual plan per-patient drug cost for tbo-filgrastim and filgrastim-sndz formulations were substantially less expensive than pegfilgrastim for an average treatment cycle. This analysis estimated an annual US health plan cost savings of over $5.5 million or more than $5.50 PMPY following an overall 7.6% utilization shift from long-acting to short-acting G-CSFs. DisclosuresJames:Teva Pharmaceuticals: Consultancy. Trautman:Teva Pharmaceuticals: Consultancy. Szabo:Teva Pharmaceuticals: Employment. Tang:Teva Pharmaceuticals: Employment.

Comparative Cost-Efficiency Analysis of Granulocyte Colony-Stimulating Factors for Use in Chemotherapy Patients in the United States

Introduction: Granulocyte colony-stimulating factors (G-CSFs), when used to reduce the incidence, severity, and duration of febrile neutropenia (FN) in chemotherapy patients, may subsequently reduce direct medical costs associated with FN by reducing rates of hospitalization, serious infections, and the use of broad-spectrum antibiotics. While the cost per chemotherapy cycle for short-acting G-CSFs (ie, filgrastim [Neupogen®], filgrastim-sndz [Zarxio®], and tbo-filgrastim [Granix®]) depends on the frequency and number of doses administered and dose used (ie, 300 mcg or 480 mcg), the cost for the long-acting G-CSF pegfilgrastim (Neulasta® 6 mg) is relatively consistent, as it is dosed once per chemotherapy cycle and is effective for 14 days. Given this difference, the extent and duration required for short-acting G-CSF treatment determine the cost-efficiency of these agents relative to pegfilgrastim, when considering similar efficacy and safety across products. This cost-efficiency analysis evaluated the effective daily cost of G-CSFs per chemotherapy cycle, from a US payer perspective.Methods: An interactive model was developed to simulate the relative cost for one chemotherapy cycle from 1 to 14 days for all currently marketed G-CSF products indicated to decrease the incidence or reduce the duration of FN in patients with non-myeloid malignancies treated with myelosuppressive chemotherapy. All agents were assumed to be provided at the health care provider (HCP) office, purchased through the patient's medical benefit, and administered by the HCP. An administration cost for each injection was included. Base-case data were derived from publicly available resources. Daily cost for short-acting G-CSFs was calculated using single dose drug acquisition cost and one administration fee per day, while daily cost for pegfilgrastim was calculated using the drug acquisition cost for one injection plus one administration cost. Additionally, the acquisition cost for short-acting agents was weighted according to the national utilization for low- (300 mcg) vs high-dose (480 mcg) products.Results: The cost of tbo-filgrastim treatment ranged from $312.96 (1 dose) to $4381.47 (14 doses), the cost of filgrastim-sndz treatment ranged from $351.30 to $4918.23, and the cost of filgrastim treatment ranged from $475.24 to $6653.33, compared with $4527.93 for one injection of pegfilgrastim. Tbo-filgrastim is cost-efficient compared with pegfilgrastim through 14 doses. Pegfilgrastim becomes cost-efficient compared with filgrastim-sndz at 13 doses and with filgrastim at 10 doses.Conclusion: Real-world data suggest that short-acting G-CSF products are used fewer than 14 days per chemotherapy cycle in clinical practice, while one dose of pegfilgrastim is efficacious for 14 days. Using acquisition costs plus administration costs for the injections, without considering the additional impact of health plan-contracted rates and manufacturer rebates for the drugs themselves, tbo-filgrastim is cost-efficient for a complete 14-day chemotherapy cycle compared with pegfilgrastim, while filgrastim-sndz and filgrastim are cost-efficient compared with pegfilgrastim through 12 doses and 9 doses, respectively. That is, short-acting products are more cost-efficient than pegfilgrastim in any chemotherapy cycle if fewer than 10 doses are needed. This finding assumes equal efficacy and safety among G-CSFs, and that all other chemotherapy-related patient characteristics are otherwise equal, including clinical appropriateness of prescribed duration of short-acting G-CSFs. G-CSFs reduce FN-associated direct medical costs and may differ in their ability to further reduce total direct medical costs of care for chemotherapy-treated patients when daily cost is considered in conjunction with necessary days of therapy. [Display omitted] DisclosuresJames:Teva Pharmaceuticals: Consultancy. Trautman:Teva Pharmaceuticals: Consultancy. Szabo:Teva Pharmaceuticals: Employment. Tang:Teva Pharmaceuticals: Employment.

Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies in a real-world setting.

e24072 Background: The prophylaxis of neutropenia has been evolving from short acting granulocyte colony-stimulating factors (G-CSFs) to long acting G-CSFs. The safety and effectiveness of long acting G-CSF in a real-world setting were still lacking. Methods: We performed a multi-center, non-interventional, real-world study to explore the tolerability and effectiveness of mecapegfilgrastim. Different prophylactic strategy (primary or secondary prophylaxis) were compared. The effect of mecapegfilgrastim by means of continuous administration was also explored. Results: This study included 638 patients who had complete the study from May 2019 to November 15, 2020. About half of the participants were breast cancer patients. The mean age of the patients were 56 years. The most frequently reported adverse event possibly related to study drug was white blood cell increase (6.2 %). No unexpected adverse events were reported. Overall, thirty-six (5.6 %) patients experienced grade ≥ 3 neutropenia in chemotherapy cycle one. The patients in the primary and secondary prophylaxis subgroups had incidence of grade ≥ 3 neutropenia of 4.3 % and 9.2 % in chemotherapy cycle one respectively. There was a decreasing trend of neutropenia from cycle one to cycle four when mecapegfilgrastim were administrated continuously. Conclusions: The mecapegfilgrastim was well tolerable and no unexpected adverse events were observed in real-world setting. Primary prophylaxis using mecapegfilgrastim had lower incidence of neutropenia than secondary usage.

Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies: a real-world study.

BackgroundChemotherapy-induced neutropenia is commonly encountered in clinical practice. The management of neutropenia has been evolving from short-acting granulocyte colony-stimulating factors (G-CSFs) to long-acting G-CSFs. However, an evaluation of the safety and effectiveness of long-acting G-CSFs in clinical practice is still lacking.MethodsThis multicenter, non-interventional study was aimed at exploring the safety and effectiveness of mecapegfilgrastim in different cancer patients in China. All patients provided written informed consent prior to the study and were treated according to routine clinical practice. Different prophylactic strategies (primary or secondary prophylaxis) were also compared.ResultsThis study included 638 patients from May 2019 to November 2020. More than half of the participants were breast cancer patients. The mean age of all the patients was 56 years. White blood cell increase (6.2%) was the most frequently reported adverse event (AE) possibly related to the study drug. No unexpected AEs were reported. Grade ≥3 neutropenia in chemotherapy treatment cycle 1 was reported in 36 (5.6%) patients. Incidence of grade ≥3 neutropenia in cycle 1 in the primary and secondary prophylaxis subgroups were of 4.3% and 9.2%, respectively. A decreasing trend of severe neutropenia incidence was observed from cycle 1 to cycle 4.ConclusionsMecapegfilgrastim was generally well tolerated, and no unexpected AEs were observed in this study. Primary administration of mecapegfilgrastim led to a lower incidence of neutropenia than did secondary administration. Continuous administration of mecapegfilgrastim could keep the incidence of neutropenia to a relatively low level.

Abstract PS9-50: A multicenter, prospective, observational study to determine the incidence of febrile neutropenia (FN), persistence and G-CSF utilization among cancer patients at high risk for FN receiving pegfilgrastim by an on-body injector (OBI) versus other FN prophylaxis strategies: An interim analysis

Abstract Background Pegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) shown to effectively reduce the risk of chemotherapy-induced FN. Pegfilgrastim should be administered on the day after chemotherapy completion (Lyman, Cancer, 2017). For patient convenience, an OBI was developed to deliver pegfilgrastim 27 hours after OBI application on the day of chemotherapy. Real-world data on whether OBI improves patient persistence, compliance, and outcomes are limited. To address this, a multicenter, prospective, observational study was conducted to describe the incidence of FN, persistence, and G-CSF utilization among patients treated with myelosuppressive chemotherapy for non-myeloid malignancies who received pegfilgrastim by OBI or other physician choice options for FN prophylaxis. Here, we report the interim results of the study. Methods Adult patients with breast, prostate, lung cancer, or non-Hodgkin’s lymphoma were stratified into 2 groups, curative or palliative intent, and classified into subgroups of FN prophylaxis based on the first chemotherapy cycle: receiving pegfilgrastim OBI (OBI group) vs other options (Other group; options: pegfilgrastim or biosimilar pegfilgrastim prefilled syringe [PFS], daily filgrastim, no G-CSF) up to 4 planned chemotherapy cycles. Additional eligibility criteria included a life expectancy of &amp;gt;6 months, chemotherapy with high (&amp;gt;20%) FN risk or intermediate (10%-20%) FN risk with ≥1 risk factor administered once every 3 or 4 weeks, and no radiation &amp;lt;2 weeks before enrollment. The prespecified analysis was based on the first 2,000 enrolled patients who completed up to 4 chemotherapy cycles. The primary endpoint is the incidence of FN (defined as absolute neutrophil count [ANC] &amp;lt;1,000 × 106/L and one of the following occurring within 24 hours of decreased ANC: temperature &amp;gt;38°C, use of intravenous antibiotics, or use of oral antibiotics). The clinical study team was blinded to FN per group at the time of analysis. Secondary endpoints include persistence (defined as G-CSF support for all chemotherapy cycles regardless of the timing of administration). G-CSF utilization was included as an exploratory endpoint. Results For the analysis, 1,930 patients were eligible (OBI, 1208; Other, 722). Patients were characterized in table 1 regarding sex, age, tumor type, and FN risk of chemotherapy regimens administered. Most patients were female (OBI, 82.0%; Other, 71.7%). The most common tumor type was breast (OBI, 72.4%; Other, 57.5%). The proportion of patients undergoing chemotherapy regimens with high FN risk was higher in the OBI group than in the Other group. The overall incidence of FN was 7.3% (95% confidence interval [CI], 6.1%-8.4%). In the Other group, 60.5% of patients received pegfilgrastim PFS, 7.6% received a short-acting G-CSF, and 30.6% did not receive G-CSF support in the first cycle. Persistence to G-CSF support was 93.5% (95% CI, 92.2%-94.9%) for the OBI group and 56.9% (53.3%-60.5%) for the Other group. Updated data will be presented at the meeting. Conclusions The OBI improved adherence to clinically appropriate G-CSF support across all chemotherapy cycles. However, approximately a third of patients did not receive primary prophylaxis with G-CSF despite being considered as a high risk for FN. CharacteristicOn-Body Injector (N=1,208)Other Physician Choice Options (N=722)Sex, n (%)Male218 (18.0)204 (28.3)Female990 (82.0)518 (71.7)Age&amp;lt;65 years, n (%)679 (56.2)397 (55.0)Median, years63.062.0Tumor type,a n (%)Breast874 (72.4)415 (57.5)Non-Hodgkin’s lymphoma178 (14.7)142 (19.7)Lung107 (8.9)104 (14.4)Prostate49 (4.1)51 (7.1)FN risk of chemotherapy, n (%)High777 (64.3)330 (45.7)Intermediate376 (31.1)326 (45.2)Unknown55 (4.6)66 (9.1)aTen patients were missing a tumor type in the Other Physician Choice Options group. FN, febrile neutropenia Citation Format: Reshma L. Mahtani, Jeffrey Crawford, Robert Rifkin, David Dale, Alan Brookhart, Prasad L. Gawade, Sandra Lewis, Tatiana Lawrence, Rajesh Belani, Gary H. Lyman. A multicenter, prospective, observational study to determine the incidence of febrile neutropenia (FN), persistence and G-CSF utilization among cancer patients at high risk for FN receiving pegfilgrastim by an on-body injector (OBI) versus other FN prophylaxis strategies: An interim analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-50.

Patient Characteristics and Utilization Patterns of Short-Acting Recombinant Granulocyte Colony-Stimulating Factor (G-CSF) Biosimilars Compared to Their Reference Product.

BackgroundData on short-acting recombinant granulocyte colony-stimulating factor (G-CSF) biosimilar utilization from claims data in the USA are limited.ObjectiveTo evaluate patient baseline characteristics and utilization patterns for short-acting G-CSF products with particular focus on the assessment of filgrastim biosimilar usage relative to the originator product.Patients and methodsWe examined filgrastim, filgrastim-sndz, and tbo-filgrastim use among adult patients between January 2012 and March 2019 across the five health-plan research partners in the BBCIC Distributed Research Network. The publicly available Sentinel System analytic toolkit was used to perform the distributed analyses.ResultsWe evaluated over 38 million eligible health-plan members representing more than 88 million person-years of data. We identified 45,204 incident treatment episodes, including 33,118 episodes with filgrastim, 6525 episodes with filgrastim-sndz, and 5,561 episodes with tbo-filgrastim. We observed that the demographic and clinical characteristics of users were comparable across products. While total use of all filgrastim products remained consistent, the proportion of incident episodes of the originator filgrastim steadily decreased since 2014, with filgrastim-sndz and tbo-filgrastim making up the difference. Utilization for the G-CSF biosimilar, filgrastim-sndz, increased from 40 (1%) of 6823 total filgrastim product episodes in 2015, to 2486 (44%) of a total 5668 episodes of filgrastim products in 2018 (partial data for 2018).ConclusionNew episodes of short-acting biosimilar filgrastim products have increased over time while the overall number of new users remained flat. Although barriers to biosimilar use in oncology have been noted, uptake has begun and continues to grow.

Introduction of biosimilar pegfilgrastim in France: Economic analysis of switching from originator.

To assess the economic impact of introducing biosimilar pegfilgrastim compared to the current standard granulocyte colony-stimulating factor (G-CSF) practice in France. A budget impact model was developed to investigate the impact of introducing pegfilgrastim biosimilar over 5 years. The model analysed drug acquisition costs, ambulatory costs, as well as costs associated with poor outcomes, and compared the current standard practice of long-acting and short-acting G-CSF to a revised practice including pegfilgrastim biosimilar in addition to standard practice treatments. The cost of switching to pegfilgrastim biosimilar, within a pharmacy setting, was analysed within the model using data from a survey of French pharmacists. The budget impact model calculated a cost saving of €51,007,531 over 5 years switching from the current standard practice to pegfilgrastim biosimilar. A sensitivity analysis accounting for variation in pegfilgrastim biosimilar uptake of 1) 15% in year 1 and 1% in years 2-5 and 2) 15% in years 1-5, estimated savings ranging between €29,377,784 and €79,847,194, respectively. A further analysis predicted cost savings of €287,344,835 over 5 years with the extension of pegfilgrastim biosimilar, at an uptake of 15% in year 1 and 7% in years 2-4, to both long-acting and short-acting G-CSF groups compared to unchanged current practice. The introduction of pegfilgrastim biosimilar will help to reduce cost and alleviate some of the financial pressure on the French healthcare system.

Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure.

Febrile neutropenia (FN) is a serious complication of chemotherapy, which can cause significant morbidity and mortality, result in dose delays and reductions and, ultimately, reduce cancer survival. Over the past decade, the availability of biosimilar filgrastim (short-acting granulocyte colony-stimulating factor [G-CSF]) has transformed patient access, with clear evidence of clinical benefit at preventing FN at reduced costs. In 2019, seven biosimilar pegfilgrastims (long-acting G-CSFs) were licensed, creating optimal market conditions and choice for prescribers. FN affects up to 117 per 1000 cancer patients, with mortality rates in the range of 2–21%. By reducing FN incidence and improving chemotherapy relative dose intensity (RDI), G-CSF has been associated with a 3.2% absolute survival benefit. Guidelines recommend primary prophylaxis and that filgrastim be administered for 10–14 days, while pegfilgrastim is administered once per cycle. When taken according to the guidelines, pegfilgrastim and filgrastim are equally effective. However, in routine clinical practice, filgrastim is often under-dosed (< 7 days) and has been shown to be inferior to pegfilgrastim at reducing FN incidence, hospitalisations and maintaining RDI. Once-per-cycle administration with pegfilgrastim might also aid patient adherence. The introduction of biosimilar pegfilgrastim should instigate a rethink of neutropenia management. Biosimilar pegfilgrastim offers countries using biosimilar filgrastim opportunities to improve adherence and thus cancer survival, whilst offering economic benefits for countries using reference pegfilgrastim. These benefits can be realised in full if biosimilar pegfilgrastim becomes part of routine clinical practice supported by drug and therapeutic committees implementing guidelines with multidisciplinary support in the hospital.Electronic supplementary materialThe online version of this article (10.1007/s40259-020-00411-4) contains supplementary material, which is available to authorized users.

Patterns of granulocyte colony\u2013stimulating factor prophylaxis in patients with cancer receiving myelosuppressive chemotherapy

PurposeTo evaluate patterns of primary prophylactic (PP) granulocyte colony–stimulating factor (G-CSF) use following chemotherapy by cancer type and febrile neutropenia (FN) risk.MethodsUsing a commercial administrative database, we identified adult patients diagnosed with breast, colorectal, lung, ovarian cancer, or non-Hodgkin lymphoma (NHL) who initiated chemotherapy with high risk (HR) or intermediate risk (IR) for FN between January 1, 2013, and August 31, 2017. We describe use of PP-G-CSF, proportion completing all their cycles with pegfilgrastim, timing of pegfilgrastim, and duration of short-acting G-CSF.ResultsAmong 22,868 patients (breast 11,513; colorectal 3765; lung 4273; ovarian 1287; and NHL 2030), 36.8% received HR and 63.2% received IR (64.4% of whom had ≥ 1 risk factor [RF] for FN). Proportions of patients receiving PP-G-CSF in the first cycle were 76.1%, 28.2%, and 26.4% among patients receiving HR, IR, and IR plus ≥ 1 RF, respectively. Among breast cancer patients receiving HR regimens and initiating PP-pegfilgrastim, 60.4% (95% confidence interval [CI] 57.2–63.6%) initiating via on-body injector (OBI) and 51.9% (95% CI 48.0–55.8%) initiating via prefilled syringe (PFS) completed all their cycles with OBI and PFS, respectively. Among all cycles with PP-PFS, 8.5% received PFS on the same day as chemotherapy completion. Mean administrations/cycle were 3.2 (standard deviation [SD] 2.3) for filgrastim, 3.0 (SD 1.6) for filgrastim-sndz, and 4.3 (SD 2.5) for tbo-filgrastim.ConclusionsThere is under- and mistimed use of PP-G-CSF among patients at HR for FN. Novel pegfilgrastim delivery devices could help breast cancer patients at HR for FN complete all their cycles with timely prophylaxis.

Efficacy and tolerability of granulocyte colony-stimulating factors in cancer patients after chemotherapy: A systematic review and Bayesian network meta-analysis

The optimum granulocyte colony-stimulating factor (G-CSF) treatment for cancer patients after being treated with cytotoxic chemotherapy remains unknown. Therefore, a systematic review and Bayesian network meta-analysis were performed to assess the efficacy and tolerability of 11 G-CSF drugs on patients after chemotherapy. A total of 73 randomized controlled trials (RCTs) containing 15,124 cancer patients were included for the final network meta-analysis. Compared with pegfilgrastim, there were a higher risk with filgrastim for incidence of febrile neutropenia (FN) (OR [95% CI]: 1.63 [1.07, 2.46]), and a higher risk with short-acting G-CSF (S-G-CSF) biosimilar and lenograstim for incidence of bone pain (BP) (OR [95% CI]: 6.45 [1.10, 65.73], 5.12 [1.14, 26.12], respectively). Mecapegfilgrastim, lipegfilgrastim and balugrastim were best G-CSF drugs in reducing FN (cumulative probabilities: 58%, 15%, 11%, respectively). S-G-CSF biosimilar, empegfilgrastim, and long-acting G-CSF (L-G-CSF) biosimilar were best G-CSF drugs in reducing severe neutropenia (SN) (cumulative probabilities: 21%, 20%, 15%, respectively). Mecapegfilgrastim, balugrastim, lipegfilgrastim and L-G-CSF biosimilar were best G-CSF drugs in reducing BP (cumulative probabilities: 20%, 14%, 8%, 8%, respectively). Mecapegfilgrastim, lipegfilgrastim and balugrastim might be the most appreciate G-CSF drugs with both good efficacy and tolerability when treating cancer patients after cytotoxic chemotherapy.

The prophylactic effects of long-acting granulocyte colony-stimulating factor for febrile neutropenia in newly diagnosed patients with epithelial ovarian cancer: a randomised controlled study

ObjectiveThis study explored the prophylactic effects of long-acting granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia (FN) in newly diagnosed patients with epithelial ovarian cancer (EOC).MethodsPatients were randomised into a study...

Risk of neutropenia-related hospitalization (NRH) related to duration of short-acting granulocyte colony stimulating factor (sG-CSF) for primary prophylaxis.

e18181 Background: In clinical trials, efficacy of 10–11 days of primary prophylactic (PP) sG-CSF is similar to a single dose of pegfilgrastim for preventing febrile neutropenia (FN). However, most patients receive &lt; 10 days of PP sG-CSF in clinical practice. This study assessed the effect of PP sG-CSF duration on the risk of NRH. Methods: Using Medicare 20% sample data, we conducted a nested case-control study within a cohort of patients aged ≥66 y with breast, colorectal, lung, ovarian, or prostate cancer or NHL who initiated first cycle of chemotherapy 1/1/2008–9/30/2016, had ≥1 y continuous coverage in Medicare parts A and B before cycle day 1 (baseline), and received PP sG-CSF. We identified NRH cases (ICD-9, 288.0X; ICD-10, D70.X) from cycle day 5 to end of cycle 1. We matched each case to up to 4 controls based on age (± 1 y), tumor type, regimen risk for FN (intermediate/high [ &gt; 10%], other), and year using incidence density sampling. Duration of sG-CSF (days of use from cycle day 1 to the day before case date) was categorized as &lt; 5 and ≥5 days. We used conditional logistic regression adjusted for race, sex, and Charlson comorbidity index (CCI) at baseline to estimate relative risk of NRH related to duration of sG-CSF. Results: Of 1431 patients receiving PP sG-CSF, 68 cases matched 231 controls. Cases were similar to controls in age (76 vs 75 y), tumor type (NHL, 62% vs 62%; lung cancer, 25% vs 25%), intermediate-/high-risk regimen (65% vs 67%), and male sex (50% vs 48%) but had slightly higher CCI (3.9 vs 3.3). The percentage of patients with ≥5 days of PP sG-CSF use was 26% in cases and 41% in controls. The adjusted OR (95% CI) for NRH was 0.48 (0.25–0.93) for ≥5 vs &lt; 5 days of PP sG-CSF; results were consistent across sensitivity analyses (Table). Conclusions: Among elderly cancer patients receiving PP sG-CSF, ≥5 days of sG-CSF use was associated with substantial reduction in the risk of NRH.[Table: see text]

Patient-Administered Biologic and Biosimilar Filgrastim May Offer More Affordable Options for Patients with Nonmyeloid Malignancies Receiving Chemotherapy in the United States: A Budget Impact Analysis from the Payer Perspective.

Granulocyte colony-stimulating factors (G-CSFs) are often administered to reduce the incidence, severity, and duration of febrile neutropenia (FN) in chemotherapy patients. Tbo-filgrastim and filgrastim-sndz represent a follow-on biologic and a biosimilar version, respectively, of the short-acting G-CSF filgrastim with comparable efficacy and safety. To estimate the budget impact of increasing use of patient-(home-) administered tbo-filgrastim and filgrastim-sndz from a U.S. payer perspective. An interactive budget impact model was developed to estimate the changes in drug cost associated with projected increases in the market share of tbo-filgrastim from 5% to 10% and of filgrastim-sndz from 10% to 12% (with a corresponding decrease in filgrastim market share from 85% to 78%) for a 1 million-member health plan among patients with nonmyeloid malignancies receiving chemotherapy with a high risk of FN. Patient self-administration at home was assumed for 20% of patients receiving short-acting G-CSF treatment; all products were purchased through the patient's pharmacy benefit and were assumed to have tier 3 formulary status with a patient copay of $54 per prescription. Base-case data were derived from publicly available resources. The total plan budget impact was calculated using a 1-year time horizon, along with the differences in per member per month and per member per year (PMPY) costs between the current and future scenarios. The effective annual per-patient drug cost to the plan totaled between $16,961 and $27,199, depending on dosage and packaging, for tbo-filgrastim; between $16,216 and $26,015 for filgrastim-sndz; and between $19,134 and $30,663 for filgrastim. The estimated total annual plan cost associated with patient-administered short-acting G-CSFs was $53,298,217 (PMPY = $53.30) in the current scenario and $52,828,832 (PMPY = $52.82) in the future scenario. Cost savings totaled $469,385 (PMPY = $0.48). The model was most sensitive to changes in the percentage of patients self-administering G-CSF at home and to the wholesale acquisition cost for filgrastim. The effective annual plan per-patient drug costs for tbo-filgrastim and filgrastim-sndz were 11% and 15% lower than filgrastim, respectively. The present analysis estimated an annual U.S. health plan cost savings approaching $0.5 million following increases in market shares of approximately 5% for tbo-filgrastim and 2% for filgrastim-sndz. This study was sponsored by Teva Branded Pharmaceutical Products R & D, which participated in the study design, data interpretation and analysis, the writing of the report, and the decision to submit. Aventine Consulting received consulting fees from Teva Pharmaceuticals and developed the cost model and provided data analysis support. Trautman and James are employed by Aventine Consulting. Szabo and Tang are employed by Teva Pharmaceuticals.