[Timing of Administration of Pegfilgrastim and Prophylaxis for Febrile Neutropenia for Patients with Early Breast Cancer Receiving Chemotherapy].

Febrile neutropenia(FN)causes a prolonged treatment schedule and decreased relative dose intensity(RDI)during cancer chemotherapy, which adversely affects prognosis. In recent years, dose-dense(dd)chemotherapy has been used as adjuvant chemotherapy for patients with breast cancer based on the results of improved disease-free survival according to meta-analysis data. Regarding neoadjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, taxanes and trastuzumab with the addition of pertuzumab have shown higher pathological complete response rates and elevated incidences of FN. One hundred seventy-six patients received pegfilgrastim(PEG)prophylaxis between January 2011 and January 2023. Until 2019, the median day of PEG prophylaxis was day 4 from chemotherapy completion(days 2- 3, 14 cases; day 4, 41 cases; and day 5, 8 cases)with antibiotic prophylaxis in 58 patients(92%). FN was observed in 19 cases(30%). The RDIs of TC and FEC were 96.8% and 96.0%, respectively. Meanwhile, the median day of PEG prophylaxis after 2020 was day 2 from chemotherapy completion(days 2-3, 108 cases; day 4, 4 cases; and day 5, 1 case)without antibiotic prophylaxis. FN was not observed in any of the cases. The RDI of all regimens was 99.7%. Although there were some differences in chemotherapy regimens, an earlier timing of PEG prophylaxis(especially 24-48 hours from chemotherapy completion)has been shown to reduce the incidence of FN and increase the RDI.

Optimal timing of prophylactic pegylated G-CSF after chemotherapy administration for patients with cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

INTRODUCTION: The timing of prophylactic pegylated granulocyte colony-stimulating factor (G-CSF) administration during cancer chemotherapy varies, with Day 2 and Days 3-5 being the most common schedules. Optimal timing remains uncertain, affecting efficacy and adverse events. This systematic review sought to evaluate the available evidence on the timing of prophylactic pegylated G-CSF administration. METHODS: Based on the Minds Handbook for Clinical Practice Guideline Development, we searched the PubMed, Ichushi-Web, and Cochrane Library databases for literature published from January 1990 to December 2019. The inclusion criteria included studies among the adult population using pegfilgrastim. The search strategy focused on timing-related keywords. Two reviewers independently extracted and assessed the data. RESULTS: Among 300 initial search results, only four articles met the inclusion criteria. A meta-analysis for febrile neutropenia incidence suggested a potential higher incidence when pegylated G-CSF was administered on Days 3-5 than on Day 2 (odds ratio: 1.27, 95% CI 0.66-2.46, p = 0.47), with a moderate certainty of evidence. No significant difference in overall survival or mortality due to infections was observed. The trend of severe adverse events was lower on Days 3-5, without statistical significance (odds ratio: 0.72, 95% CI 0.14-3.67, p = 0.69) and with a moderate certainty of evidence. Data on pain were inconclusive. CONCLUSIONS: Both Day 2 and Days 3-5 were weakly recommended for pegylated G-CSF administration post-chemotherapy in patients with cancer. The limited evidence highlights the need for further research to refine recommendations.

Filgrastim biosimilar (EP2006): A review of 15 years' post-approval evidence.

Filgrastim is approved for several indications, including reduction of the incidence and duration of chemotherapy-induced neutropenia and for stem cell mobilization. The filgrastim biosimilar, EP2006, has been available in Europe since 2009, and in the United States since 2015. In this time, preclinical and clinical data used to support the approval of EP2006 have been published. These data established the biosimilarity of EP2006 to reference filgrastim in terms of structure, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Additional real-world evidence studies have also demonstrated equivalent efficacy and safety of EP2006 compared with reference filgrastim, both in the reduction of neutropenia and in stem cell mobilization in clinical practice. This review summarizes these preclinical, clinical, and real-world data, as well as the available cost-effectiveness data, for EP2006 since its approval 15 years ago.

A Randomized, Open-Label Study Conducted to Evaluate the Bioequivalence of Pegfilgrastim-cbqv On-Body Injector Versus Prefilled Syringe in Healthy Male Participants.

INTRODUCTION: To help prevent febrile neutropenia, pegfilgrastim-cbqv (UDENYCA®; Coherus BioSciences), a pegfilgrastim (NEULASTA®; Amgen) biosimilar, is administered 24-96 h after myelosuppressive chemotherapy. Delivery of pegfilgrastim-cbqv using an on-body injector (OBI) provides an alternative method of administration, affording options in drug delivery. This study aimed to establish pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence and assess the safety of pegfilgrastim-cbqv administered using an OBI compared with a prefilled syringe (PFS). METHODS: In this open-label, two-period crossover study, healthy adult male participants (N = 189) were randomly assigned 1:1 to receive pegfilgrastim-cbqv 6 mg subcutaneously using an OBI (n = 92) or a PFS (n = 95) in period 1 and then an injection via the other method in period 2. Primary PK end points were area under the concentration-time curve from time 0 to infinity, area under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum plasma concentration. Secondary PD end points, safety, immunogenicity, and tolerability were also assessed. RESULTS: The 90% confidence intervals (CIs) of the geometric mean ratios for the PK and PD end points fell within the predetermined range (80-125%), indicating PK and PD bioequivalence between pegfilgrastim-cbqv OBI and pegfilgrastim-cbqv PFS. Treatment-emergent adverse events (TEAEs) occurred in 87.8% and 75.8% of participants in the OBI and PFS groups, respectively. Most TEAEs were musculoskeletal effects. The most common OBI-related TEAE was injection site erythema (31.7%), which was mild, transient, and self-limiting. The incidence of treatment-emergent antidrug antibodies (ADAs) was similar between the OBI and PFS. ADAs had no apparent impact on PK, PD, or safety. Neutralizing antibodies were not detected in any participant. CONCLUSIONS: Results of the study showed PK and PD bioequivalence of pegfilgrastim-cbqv administered using OBI compared with PFS. OBI and PFS administration had similar safety, tolerability, and immunogenicity profiles. No unexpected safety signals were identified. Graphical Abstract available for this article.

Febrile neutropenia is when a patient has a fever and a lower-than-normal number of white blood cells. When white blood cell counts are low, patients are more susceptible to opportunistic infections as a result of their weakened immune systems. Severe febrile neutropenia can lead to the stopping or delaying of chemotherapy. The drug pegfilgrastim-cbqv is used 24­96 h after chemotherapy to stimulate the growth of white blood cells. Pegfilgrastim-cbqv is available in a single-dose prefilled syringe and in a prefilled autoinjector. If a patient cannot inject themselves with the drug, they must go to a clinic for the injection. Using an on-body injector applied to the skin that automatically injects the drug at a specific time could eliminate the need to go to the clinic. During this study, healthy adult male participants were given pegfilgrastim-cbqv through an on-body injector or a prefilled syringe to investigate if the movement of the drug into, through, and out of the body (pharmacokinetics) and the physiological action of the drug in the body (pharmacodynamics) were similar between the two injection methods. Side effects were also studied. The researchers found that the pharmacokinetics and pharmacodynamics for pegfilgrastim-cbqv given by on-body-injector or prefilled syringe were similar. The number and types of side effects were also similar. The most common side effect for the on-body injector was mild erythema at the injection site. This side effect resolved by itself. The treatment benefit and safety of pegfilgrastim-cbqv were very similar regardless of how the drug was administered.

Filgrastim and infliximab biosimilar uptake in Medicare Advantage compared with Traditional Medicare, 2016-2019.

BACKGROUND: Medicare Advantage (MA) and Traditional Medicare face different financing structures and incentives and may implement different strategies to encourage biosimilar uptake. Strategies used by health insurers can influence biosimilar uptake, which can in turn promote savings to insurers and patients. OBJECTIVE: To compare filgrastim and infliximab biosimilar uptake between MA and Traditional Medicare from 2016 to 2019 and examine biosimilar uptake by different MA carriers and plan types (Health Maintenance Organization [HMO] or Preferred Provider Organization). METHODS: We use a 2016-2019 nationally representative random 20% sample of the carrier (physician) and outpatient paid claims for Traditional Medicare data and final-action carrier and outpatient records for MA data. We compare quarterly biosimilar uptake from 2016 to 2019 for the first 2 drugs with biosimilar competition: (1) filgrastim, (Neupogen, originator), and biosimilars tbo-filgrastim (GRANIX) and filgrastim-sndz (ZARXIO), and (2) infliximab (Remicade, originator), and biosimilars infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). RESULTS: From their introduction, there was consistently greater uptake of filgrastim and infliximab biosimilars in MA compared with Traditional Medicare. By Q4 2019, filgrastim biosimilar uptake was 7.6 percentage points higher in MA (80.3%) than Traditional Medicare (72.7%). By Q4 2019, infliximab biosimilar uptake was 28.7% and 15.4% in MA and Traditional Medicare, respectively. Kaiser HMO plans were primarily responsible for the higher uptake of biosimilars in MA; in Q4 2019, filgrastim and infliximab biosimilar uptake was 98.8% and 78.8%, respectively. CONCLUSIONS: Our findings suggest that filgrastim and infliximab biosimilar uptake is greater in MA compared with Traditional Medicare, which is driven in part by particularly high uptake of biosimilars in MA Kaiser HMO plans. This highlights the need for future work to examine specific strategies and levers employed by MA Kaiser HMO plans and other insurers to increase biosimilar uptake, which can lead to cost savings for physician-administered drugs.

Granulocyte Colony-Stimulating Factor (Neupogen®; Filgrastim) Accelerates Neutrophil Recovery in a Rodent Model of Sulfur Mustard-Induced Hematologic Toxicity.

OBJECTIVE: Evidence of myelosuppression has been negatively correlated with patient outcomes following cases of high dose sulfur mustard (SM) exposure. These hematologic complications can negatively impact overall immune function and increase the risk of infection and life-threatening septicemia. Currently, there are no approved medical treatments for the myelosuppressive effects of SM exposure. METHODS: Leveraging a recently developed rodent model of SM-induced hematologic toxicity, post-exposure efficacy testing of the granulocyte colony-stimulating factor drug Neupogen® was performed in rats intravenously challenged with SM. Before efficacy testing, pharmacokinetic/pharmacodynamic analyses were performed in naïve rats to identify the apparent human equivalent dose of Neupogen® for efficacy evaluation. RESULTS: When administered 1 d after SM-exposure, daily subcutaneous Neupogen® treatment did not prevent the delayed onset of hematologic toxicity but significantly accelerated recovery from neutropenia. Compared with SM controls, Neupogen®-treated animals recovered body weight faster, resolved toxic clinical signs more rapidly, and did not display transient febrility at time points generally concurrent with marked pancytopenia. CONCLUSIONS: Collectively, this work corroborates the results of a previous pilot large animal study, validates the utility of a rodent screening model, and provides further evidence for the potential clinical utility of Neupogen® as an adjunct treatment following SM exposure.

Motixafortide: First Approval.

Motixafortide (APHEXDATM) is a selective C-X-C motif chemokine receptor 4 (CXCR4) inhibitor being developed by BioLineRx under licence from Biokine Therapeutics for the mobilization of haematopoietic stem cells (HSCs) and the treatment of various cancers. On 11 September 2023, motixafortide was approved in the USA for use in combination with filgrastim [granulocyte colony stimulating factor (G-CSF)] to mobilize HSCs to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. Motixafortide has been granted Orphan Drug Designation for the treatment of pancreatic cancer in the EU and the USA, and for the treatment of acute myeloid leukaemia in the USA. Clinical development is ongoing for the mobilization of CD34+ HSCs for gene therapy in patients with sickle cell disease. This article summarizes the milestones in the development of motixafortide leading to this first approval.

Cladribine, cytarabine, and filgrastim based regimen in relapsed or refractory acute myeloid leukemia: A systematic review and meta-analysis.

BACKGROUND: To ascertain the efficacy and safety of cladribine, cytarabine, and filgrastim-based regimen in relapsed or refractory (R/R) AML patients. METHODS: Clinical studies were searched in PubMed, Cochrane Library, Embase data. We selected available factors including complete remission (CR), overall response rate (ORR), overall survival (OS) to evaluate the efficacy, and early death (ED), and adverse events to evaluate safety. RESULTS: 15 records with 812 R/R AML patients were finally included and analyzed using the R software. Subgroups analysis was also conducted. The pooled CR rate for CLAG regimen, CLAG-M regimen, and CLAG combined with any other drugs regimen is 56% (95% CI: 46-66), 46% (95% CI: 34-56), 44% (95% CI: 26-64), respectively. The relapsed and refractory groups showed a CR rate of 68% (95% CI: 53-80), and 51% (95% CI: 45-58) with CLAG related regimens. As risk grade decreases, the pooled CR rate increases. Regarding the safety for CLAG-related protocols, systematic review was conducted. CONCLUSION: The CLAG-related regimen is an effective and safe therapy for R/R AML patients, CLAG seems to have more superiority than CLAG combined therapy, though further studies including cladribine combination treatment protocols, are still needed to confirm our results further.

Cost-effectiveness of granulocyte colony-stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) in patients with cancer.

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.

The impact of policy interventions to promote the uptake of biosimilar medicines in Belgium: a nationwide interrupted time series analysis.

BACKGROUND: The Belgian government has taken several measures to increase the uptake of biosimilars in past years. However, no formal evaluation of the impact of these measures has been made yet. This study aimed to investigate the impact of the implemented measures on biosimilar uptake. METHODS: An interrupted time series analysis was performed using an autoregressive integrated moving average (ARIMA) model with the Box-Jenkins method. All data were expressed as defined daily doses (DDD) per month/quarter and obtained from the Belgian National Institute for Health and Disability Insurance (NIHDI). Three molecules were included in the analysis: etanercept (ambulatory), filgrastim (hospital), and epoetin (hospital). A significance level of 5% was used for all analyses. RESULTS: In the ambulatory care, the effect of a financial prescriber incentive of 2019 was investigated. After this intervention, 44.504 (95% CI -61.61 to -14.812; P < 0.001) fewer etanercept biosimilar DDDs were dispensed monthly than expected in the absence of the intervention. Two interventions were modelled for biosimilars in the hospital setting. The first intervention of 2016 includes prescription targets for biosimilars and monitoring of hospitals on adequate tendering. The second intervention involves an information campaign on biosimilars. After the first intervention, a small decrease in quarterly epoetin biosimilar uptake of 449.820 DDD (95% CI -880.113 to -19.527; P = 0.05) was observed. The second intervention led to a larger increase in quarterly epoetin biosimilar uptake of 2733.692 DDD (95% CI 1648.648-3818.736; P < 0.001). For filgrastim, 1809.833 DDD (95% CI 1354.797-2264.869; P < 0.001) more biosimilars were dispensed immediately after the first intervention and 151.639 DDD (95% CI -203.128 to -100.150; P < 0.001) fewer biosimilars each quarter after the first intervention. An immediate and sustained increase of 700.932 DDD (95% CI 180.536-1221.328; P = 0.016) in quarterly biosimilar volume was observed after the second intervention. All other parameter estimates were not statistically significant. CONCLUSIONS: The results of this study suggest that the impact of past policy interventions to increase the uptake of biosimilars has been variable and limited. A holistic policy framework is required to develop a competitive and sustainable off-patent biologicals market in Belgium.

Real-world data analysis of perioperative chemotherapy patterns, G-CSF use, and FN status in patients with early breast cancer.

PURPOSE: This study aimed to describe perioperative chemotherapy patterns, granulocyte colony-stimulating factor (G-CSF) use, and febrile neutropenia (FN) status in patients with early breast cancer (EBC) using real-world data in Japan. METHODS: This retrospective observational study used anonymized claims data. The included patients were ≥ 18 years old, were female, and had breast cancer diagnosis and surgery records between January 2010 and April 2020. Measures included perioperative chemotherapy, G-CSF use (daily and primary prophylaxis [PP]), and FN and FN-related hospitalization (FNH), all examined annually. Perioperative chemotherapy was examined separately for human epidermal growth factor receptor 2-positive/negative (HER2±). A multivariate logistic regression was used to explore the factors associated with FNH. RESULTS: Of 32,597 patients, those with HER2 + EBC treated with anthracycline-based regimens followed by taxane + trastuzumab + pertuzumab increased since 2018, and those with HER2 - EBC treated with doxorubicin/epirubicin + cyclophosphamide followed by taxane and dose-dense regimens increased after 2014. The proportion of patients prescribed daily G-CSF declined after 2014, whereas that of pegfilgrastim PP increased. The incidence proportion of FN remained at approximately 24-31% from 2010 to 2020, while that of FNH declined from 14.5 to 4.0%. The odds of FNH were higher in those aged ≥ 65 years and lower with pegfilgrastim PP administration. CONCLUSION: Despite the increasing use of escalated regimens in the last 5-6 years, FNH continuously declined, and the odds of FNH were lower among patients treated with pegfilgrastim PP. These results may suggest the contribution of PP in part to suppressing FNH levels over the last 5-6 years.

Provider barriers in uptake of biosimilars: case study on filgrastim.

In this article, we used administrative claims data from the OptumLabs Data Warehouse and American Hospital Association Annual Survey data to examine associations between hospital characteristics and uptake of biosimilar granulocyte colony-stimulating factor treatments. We found that 340B-participating hospitals and non-rural referral center (RRC) hospitals that reported owning rural health clinics were less likely to administer the lower-cost biosimilars, whereas the opposite was true for hospitals that are RRCs. To our knowledge, our study offers a first look at an underappreciated source of disparities in access to lower-cost medications such as biosimilars. Results from our study reveal opportunities for targeted policies to encourage adoption of lower-cost treatments, particularly among hospitals that serve rural communities where patients often have fewer choices in care site.

The impact of new and emerging agents on outcomes for febrile neutropenia: addressing clinical gaps.

PURPOSE OF REVIEW: While chemotherapy treatment options for patients with solid and hematologic malignancies have dramatically improved over recent years, chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) remain major barriers to delivering treatment at full doses and optimal timing. Despite concurrent advances in granulocyte colony-stimulating factor (G-CSF) administration, multiple barriers to the administration of and disparities in the access to these agents remain. The introduction of new, emerging agents, including biosimilars and novel therapies show promise in improving outcomes for CIN. RECENT FINDINGS: The introduction of biosimilar filgrastim products has improved access to G-CSF administration by driving marketplace competition and has reduced costs for both patients and healthcare systems without sacrificing efficacy. Emerging therapies to address similar issues include long-acting G-CSF products, efbemalenograstim alfa and eflapegrastin-xnst, as well as agents with novel mechanisms of action, plinabulin and trilaciclib. These agents have shown efficacy and cost-saving benefits in certain populations and disease groups. SUMMARY: Multiple emerging agents show promise in decreasing the burden of CIN. Use of these therapies will reduce access disparities and will improve outcomes for patients with cancer receiving cytotoxic chemotherapy. Many ongoing trials are underway to evaluate the roles of these agents for more widespread use.

Efficacy and Cost-effectiveness of Pegfilgrastim for Preventing Febrile Neutropenia During Docetaxel, Cisplatin, and 5-Fluorouracil Therapy for Esophageal Cancer.

BACKGROUND/AIM: The docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events, such as febrile neutropenia (FN), is high. This study retrospectively examined whether pegfilgrastim treatment reduces FN development during DCF therapy. PATIENTS AND METHODS: This study evaluated 52 patients who were diagnosed with esophageal cancer and underwent DCF therapy at Jikei Daisan Hospital, Tokyo, Japan, between 2016 and 2020. They were divided into non-pegfilgrastim and pegfilgrastim-treated groups, and side-effects of chemotherapy and cost-effectiveness of pegfilgrastim were examined. RESULTS: Eighty-six cycles of DCF therapy were conducted (33 and 53 cycles, respectively). FN was observed in 20 (60.6%) and seven (13.2%) cases, respectively (p<0.001). The lowest absolute neutrophil count during chemotherapy was significantly lower in the non-pegfilgrastim group (p<0.001), and the number of days until improvement from nadir was significantly shorter in the pegfilgrastim group (9 vs. 11 days; p<0.001). No significant difference was found in the onset of grade 2 or more adverse events by Common Terminology Criteria for Adverse Events. However, renal dysfunction was significantly lower in the pegfilgrastim group (30.7% vs. 60.6%, p=0.038). Hospitalization costs were also significantly lower in this group (692,839 vs. 879,431 Japanese yen, p=0.028). CONCLUSION: This study revealed the usefulness and cost-effectiveness of pegfilgrastim in prevention of FN in patients treated with DCF.

Effectiveness of biosimilar pegfilgrastim in patients with multiple myeloma after high-dose melphalan and autologous stem cell transplantation.

Multiple myeloma (MM) is the main indication for autologous stem cell transplantation (ASCT). Novel supportive therapies (e.g., granulocyte colony-stimulating factor) have significantly improved post-ASCT-related mortality; however, data on biosimilar pegfilgrastim-bmez (BIO/PEG) in this setting is lacking. This prospective cohort study compared Italian patients with MM who received BIO/PEG post-ASCT with data collected retrospectively from historical control groups from the same center who received either filgrastim-sndz (BIO/G-CSF) or pegfilgrastim (PEG; originator). The primary endpoint was time to neutrophil engraftment (three consecutive days with an absolute neutrophil count ≥ 0.5 × 109/L). Secondary endpoints included incidence and duration of febrile neutropenia (FN). Of the 231 patients included, 73 were treated with PEG, 102 with BIO/G-CSF, and 56 with BIO/PEG. Median age was 60 years and 57.1% were male. Neutrophil engraftment was reached after a median of 10 days in the BIO/PEG and PEG groups and 11 days in the BIO/G-CSF group. Among patients who achieved neutrophil engraftment earlier than this (i.e., day 9), 58% (29/50) were on PEG; of those who achieved it later (i.e., day 11), 80.8% (59/73) were on BIO/G-CSF. FN incidence was higher with BIO/G-CSF (61.4%) versus PEG (52.1%) or BIO/PEG (37.5%) (p = 0.02 among groups). Patients on BIO/PEG had less frequent grade 2-3 diarrhea (5.5%) compared with BIO/G-CSF (22.5%) or PEG (21.9%); grade 2-3 mucositis was most frequent in the BIO/G-CSF group. In conclusion, pegfilgrastim and its biosimilar displayed an advantageous efficacy and safety profile compared with biosimilar filgrastim in patients with MM post-ASCT.

Biosimilar Use Among 38 ASCO PracticeNET Practices, 2019-2021.

PURPOSE: Biosimilars offer increased patient choice and potential cost-savings, compared with originator biologics. We studied 3 years of prescribed biologics among US physician practices to determine the relationship of practice type and payment source to oncology biosimilar use. METHODS: We acquired biologic utilization data from 38 practices participating in PracticeNET. We focused on six biologics (bevacizumab, epoetin alfa, filgrastim, pegfilgrastim, rituximab, and trastuzumab) for the period from 2019 to 2021. We complemented our quantitative analysis with a survey of PracticeNET participants (prescribers and practice leaders) to reveal potential motivators and barriers to biosimilar use. We implemented logistic regression to evaluate the biosimilar use for each biologic, with covariates including time, practice type, and payment source, and accounted for clusters of practices. RESULTS: Use of biosimilars increased over the 3-year period, reaching between 51% and 80% of administered doses by the fourth quarter of 2021, depending on the biologic. Biosimilar use varied by practice, with independent physician practices having higher use of biosimilars for epoetin alfa, filgrastim, rituximab, and trastuzumab. Compared with commercial health plans, Medicaid plans had lower biosimilar use for four biologics; traditional Medicare had lower use for five biologics. The average cost per dose decreased between 24% and 41%, dependent on the biologic. CONCLUSION: Biosimilars have, through increased use, lowered the average cost per dose of the studied biologics. Biosimilar use differed by originator biologic, practice type, and payment source. There remains further opportunity for increases in biosimilar use among certain practices and payers.

Neulasta Onpro: a coup de grâce?

With the rapid decline in average sales price of reference pegfilgrastim products due to biosimilar competition, health care institutions and payers may grapple with coverage of Neulasta Onpro.

The Impact of HIV Infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Patients with Breast Cancer.

INTRODUCTION: In the South African Breast Cancer and HIV Outcomes (SABCHO) study, we previously found that breast cancer patients living with HIV and treated with neoadjuvant chemotherapy achieve lower rates of complete pathologic response than patients without HIV. We now assess the impact of comorbid HIV on receipt of timely and complete neoadjuvant and adjuvant chemotherapy. MATERIALS AND METHODS: Since June 2015, the SABCHO study has collected data on women diagnosed with breast cancer at 6 South African hospitals. We selected a sample of participants with stages I-III cancer who received ≥2 doses of neoadjuvant or adjuvant chemotherapy. Data on chemotherapies prescribed and received, filgrastim receipt, and laboratory values measured during treatment were captured from patients' medical records. We calculated the mean relative dose intensity (RDI) for all prescribed chemotherapies. We tested for association between full regimen RDI and HIV status, using linear regression to control for demographic and clinical covariates, and for association of HIV with laboratory abnormalities. RESULTS: The 166 participants living with HIV and 159 without HIV did not differ in median chemotherapy RDI: 0.89 (interquartile range (IQR) 0.77-0.95) among those living with HIV and 0.87 (IQR 0.77-0.94) among women without HIV. Patients living with HIV experienced more grade 3+ anemia and leukopenia than those without HIV (anemia: 10.8% vs. 1.9%, P = .001; leukopenia: 8.4% vs. 1.9%, P = .008) and were more likely to receive filgrastim (24.7% vs. 10.7%, P = .001). CONCLUSIONS: HIV status did not impact neoadjuvant or adjuvant chemotherapy RDI, although patients with breast cancer living with HIV experienced more myelotoxicity during treatment.

As-Required Filgrastim for Late-Onset Neutropenia Complicating Long-Term Clozapine Treatment: a Case Report.

Clozapine is considered the most effective antipsychotic for schizophrenia, but it can cause neutropenia and even agranulocytosis. We describe the first case in Hong Kong involving the use of filgrastim, a recombinant form of human granulocyte colony-stimulating factor, to enable clozapine continuation therapy for a severely ill patient with treatment-resistant schizoaffective disorder who developed recurrent neutropenia after almost 20 years of continuous clozapine therapy. Therefore, clinical vigilance is important, regardless of clozapine treatment duration. Filgrastim can facilitate long-term clozapine therapy in patients with clozapine-induced neutropenia.

Comparison of Biosimilar Filgrastim with Innovator Fligrastim for Peripheral Blood Stem Cells Mobilization, Collection of CD34+ Stem Cells, and Engraftment in Patients Undergoing Autologous and Allogeneic Stem Cell Transplantation: A Single-Center Experience.

BACKGROUND In the Middle East, there is lack of data on peripheral blood CD34+stem cells mobilization by using biosimilar filgrastim. We have been using both Neupogen and a biosimilar G-CSF) Zarzio® (as a mobilizing agent since February 2014 for both allogenic and autologous stem cell transplantations. MATERIAL AND METHODS This was a single-center retrospective study. All patients and healthy donors who received either the biosimilar G-CSF (Zarzio®) or original G-CSF (Neupogen®) for mobilization of CD34+ stem cells were included in the study. The primary goal was to determine and compare the rate of successful harvest and amount of CD34+ stem cells collected in either adult cancer patients or healthy donors between Zarzio® and Neupogen® groups. RESULTS A total of 114 patients, including 97 cancer patients and 17 healthy donors, underwent successful CD34+ stem cell mobilization using G-CSF with chemotherapy (35 with Zarzio® +chemotherapy, 39 with Neupogen® +chemotherapy) or G-CSF as monotherapy (14 with Zarzio®, 9 with Neupogen®) in autologous transplantation. In an allogeneic stem cell transplantation, successful harvest was achieved by using G-CSF monotherapy (8 with Zarzio®, 9 with Neupogen®). There was no difference between Zarzio® and Neupogen® in the amount of CD34+ stem cells collected at leukapheresis. There was no difference with regards to secondary outcomes between the 2 groups. CONCLUSIONS Our study showed that biosimilar G-CSF (Zarzio®) has comparable efficacy to the original G-CSF (Neupogen®) when used for mobilization in both autologous and allogenic stem cell transplantation and was associated with significant cost saving.