Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.

Achieving white blood cell equity: are the safety profiles of biosimilar and reference pegfilgrastims comparable?

Biosimilars can provide choices for patients and may provide cost savings; however, their uptake has been slow in the USA, in part due to limited knowledge. To provide additional confidence in US pegfilgrastim biosimilars, this narrative review compared the safety profiles of biosimilar pegfilgrastims, currently approved or filed for approval in the USA, with the EU- and US-approved reference pegfilgrastims. Headache and bone pain were common to biosimilars and reference products and occurred at a similar incidence. Clinical trial data on the safety profiles of biosimilar pegfilgrastims and reference products have demonstrated similarity and comparability, with no unexpected safety outcomes. Overall, the safety profiles of biosimilar pegfilgrastims and reference pegfilgrastims demonstrated a high degree of similarity and comparability.

Pegfilgrastim is a biologic drug (one made in living cells such as bacteria) that is given to some patients being treated for cancer. Pegfilgrastim is prescribed to reduce a patient's risk of infection due to a weakened immune system caused by various chemotherapy treatment plans. A biosimilar is a type of biologic medicine that is highly similar to a US FDA-approved reference biologic, and is often cheaper, making it more widely available to patients. As of March 2023, there are eight pegfilgrastim biosimilars (six approved and two awaiting approval by the FDA). This review compared the side effects for the reference pegfilgrastim with the biosimilar pegfilgrastims. The side effects in general and the side effects from treatment were similar for the reference pegfilgrastim and for the biosimilar pegfilgrastims, with the most common side effects being headache and bone pain. Serious side effects such as allergic reactions or problems with the spleen were very low and were also similar between the reference pegfilgrastim and the biosimilar pegfilgrastims. These results show that the safety of the biosimilar pegfilgrastims was similar to the reference pegfilgrastim, with no unexpected side effects. With comparable safety to their reference product, biosimilars have the potential to improve patient access to more affordable treatment options.

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.

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.

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.

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.

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.

Cost-efficiency analysis of conversion to biosimilar filgrastim for supportive cancer care and resultant expanded access analysis to supportive care and early-stage HER2+ breast cancer treatment in Saudi Arabia: simulation study.

AIMS: This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen and Neulastim to one of two filgrastim biosimilars (Nivestim, Zarzio); the budget-neutral expanded access to supportive care with biosimilar filgrastim and therapeutic care to ado-trastuzumab emtansine thus afforded; and the number-needed-to-convert (NNC) to provide supportive or therapeutic treatment to one patient. MATERIALS AND METHODS: Replicating prior studies, we modeled the cost-efficiencies gained from converting varying proportions of a hypothetical panel of 4,000 patients undergoing six cycles of cancer treatment from Neupogen or Neulastim to one of the two biosimilar G-CSF formulations, using national cost inputs. Cost-savings in USD were used to estimate the additional doses of biosimilar G-CSF and expanded access to ado-trastuzumab emtansine on a budget-neutral basis, and NNC to purchase one additional dose of supportive or therapeutic treatment. RESULTS: Savings from conversion from reference to a biosimilar filgrastim were $3,086,400 (Nivestim) and $3,460,800 (Zarzio). With reference pegfilgrastim, savings from conversion were $11,712,240 (Nivestim) and $12,086,640 (Zarzio). Biosimilar conversion from reference to biosimilar filgrastim enabled expanded access to ado-trastuzumab emtansine ranging from 61 patients (5 days, Nivestim) to 191 patients (14 days, Zarzio). For supportive care, biosimilar conversion enabled expanded access ranging from 8,244 patients (5 days, Nivestim) to 25,882 patients (14 days, Zarzio). For biosimilar conversion from daily filgrastim, the NNC for treatment with ado-trastuzumab emtansine decreased as days of injections increased [5 days: 395 (Nivestim), 352 (Zarzio); 14 days: 141(Nivestim), 126 (Zarzio)]. Alternately, for biosimilar conversion from single-injection pegfilgrastim to daily biosimilar filgrastim, the NNC for treatment with ado-trastuzumab emtansine rose as days of injections increased, being highest under the 14-day scenario (146, Nivestim; 130, Zarzio). CONCLUSION: This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care.

Cost comparison of filgrastim versus pegfilgrastim and pegfilgrastim biosimilars for inpatient prophylaxis of febrile neutropenia.

INTRODUCTION: The Ohio State University Comprehensive Cancer Center (The James) uses daily subcutaneous filgrastim as the inpatient granulocyte colony-stimulating factor of choice. The coordination of care associated with filgrastim can often be a barrier to patient discharge. The purpose of this study was to compare the inpatient cost of daily filgrastim to single dose pegfilgrastim and biosimilars. METHODS: Adult patients admitted to The James who received at least one dose of filgrastim between June 1, 2021 and August 31, 2021 were retrospectively identified. This study compared the inpatient cost of filgrastim and biosimilars associated with one chemotherapy cycle to the potential inpatient cost of pegfilgrastim and biosimilars based on average sales price (ASP). Additionally, the number and duration of discharge prescriptions for filgrastim was determined. RESULTS: Of the 44 unique patient encounters that met inclusion criteria, 19 received 300-mcg doses of filgrastim and 25 received 480-mcg doses. The median number of doses administered per admission was eight. If each of these patients were to instead receive the most inexpensive biosimilar, pegfilgrastim reference product, the cost would be 216% higher than with filgrastim-sndz. At discharge, 15 patients (34%) received a prescription for filgrastim to be continued for a median duration of 6 days. CONCLUSION: Based on ASP, pegfilgrastim was more costly than filgrastim. Potential rebates and negotiation power may alter the financial outlook of adding pegfilgrastim to inpatient formulary. Exploration of delays in discharge due to insurance coordination for filgrastim continuation in the outpatient setting may also impact formulary decisions.

Cost-effectiveness of pegfilgrastim versus filgrastim for prevention of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review.

BACKGROUND: Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim's value for money remains unclear. OBJECTIVE: To systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020. RESULTS: We identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe (n = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority (n = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN (> 20%). The studies considered a wide range of baseline FN risk (17-97.4%) and mortality rates (5.8-8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit. CONCLUSIONS: Most studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.

A comparative assessment of neutropenia events, healthcare resource use, and costs among cancer patients treated with lipegfilgrastim compared with pegfilgrastim in Germany.

PURPOSE: We assessed the occurrence of neutropenia and febrile neutropenia (FN) and the associated healthcare resource in cancer patients receiving myelosuppressive chemotherapy in combination with pegfilgrastim versus lipegfilgrastim. METHODS: This is a retrospective analysis using a German health insurance claims database. Adults receiving chemotherapy with a prescription code for pegfilgrastim (n = 734) or lipegfilgrastim (n = 346) were observed over a 1-year follow-up period. Patient subgroups were analyzed according to cancer type and FN risk. FN risk was based on the chemotherapy regimen and any additional neutropenia risk factors. Outcomes were adjusted via regression analysis. RESULTS: Most patients were classified as high FN risk (70.0% pegfilgrastim; 65.6% lipegfilgrastim cohort). The mean age was 58.2 years in the pegfilgrastim cohort and 58.0 years in the lipegfilgrastim cohort, with more female patients than male patients (77.3% vs 79.8%, respectively), and the majority had breast cancer (64.9% and 68.8%, respectively). Overall, 10.0% and 10.4% of patients receiving pegfilgrastim or lipegfilgrastim experienced a neutropenia event (p = 0.82), with 4.4% and 3.5% of patients experiencing a FN event (p = 0.49). The mean neutropenia event-related healthcare costs were €604 and €441 for the pegfilgrastim and lipegfilgrastim cohorts; among patients with lymphoma, these costs were significantly greater (p = 0.03) with pegfilgrastim (€1,612) versus lipegfilgrastim (€382). The mean all-cause hospitalizations were significantly (p < 0.01) higher for lymphoma patients receiving pegfilgrastim (2.76) versus lipegfilgrastim (1.60). CONCLUSION: Overall, patients treated with pegfilgrastim and lipegfilgrastim were comparable in terms of neutropenia occurrences in the 1-year follow-up. In patients with lymphoma, neutropenia event-related healthcare costs and all-cause hospitalizations were significantly higher with pegfilgrastim compared with lipegfilgrastim in this study; however, this should be interpreted with caution in light of the limited sample size and the absence of clinical information.

Patient out-of-pocket and payer costs for pegfilgrastim originator vs biosimilars as primary prophylaxis of febrile neutropenia in the first cycle among a commercially insured population.

BACKGROUND: It is unknown whether using pegfilgrastim biosimilars is cost saving in a real-world setting. OBJECTIVE: To compare medical costs including pegfilgrastim drug costs and febrile neutropenia (FN) treatment and management costs between pegfilgrastim biosimilars (pegfilgrastim-jmdb, pegfilgrastim-cbqv) and originator users for primary prophylaxis of febrile neutropenia. METHODS: A retrospective cohort study using 2019 IBM MarketScan Commercial and Medicare Supplemental databases was conducted in adult patients with cancer initiating myelosuppressive chemotherapy courses. At least 2 diagnoses of the same cancer (at least 7 days apart) were required within 30 days of the chemotherapy initiation date. Pegfilgrastim (excluding on-body injector) costs included drug costs only (excluding administration fees). FN-related costs included all FN-related health care utilizations that were defined as having neutropenia, fever, or infection diagnosis. Per-patient per-cycle (PPPC) out-of-pocket (OOP) costs, health plan costs, and total costs were compared between originator (excluding on-body injector) and biosimilars users in the first cycle. A generalized linear model and a 2-part model were used. RESULTS: A total of 1,930 patients were included, of whom 884 (45.8%) used pegfilgrastim originator, 427 (22.1%) used pegfilgrastim-jmdb, and 619 (32.1%) used pegfilgrastim-cbqv. Adjusted PPPC OOP pegfilgrastim costs in the first cycle were significantly lower for the biosimilars vs the originator ($182 for pegfilgrastim-jmdb and $159 for pegfilgrastim-cbqv vs $299 for originator, P < 0.0001 for both comparisons). However, there was no difference in health plan costs ($5,783 for pegfilgrastim-jmdb and $5,845 for pegfilgrastim-cbqv vs $5,618 for originator) and total costs. In addition, no difference was observed for adjusted PPPC FN treatment and management OOP costs, health plan costs, and total costs in the first cycle. FN treatment OOP costs were $192 for originator, $197 for pegfilgrastim-jmdb (P = 0.958), and $240 for pegfilgrastim-cbqv (P = 0.680). FN treatment health plan costs were $2,804 for originator, $2,970 for pegfilgrastim-jmdb (P = 0.692), and $2,745 for pegfilgrastim-cbqv (P = 0.879). CONCLUSIONS: In a commercially insured population, using pegfilgrastim biosimilars in the first cycle for primary prophylaxis of FN led to cost savings for patients but not payers. No difference in FN-related costs was observed.

Cost-effectiveness analysis of pegfilgrastim in patients with non-small cell lung cancer receiving ramucirumab plus docetaxel in Japan.

PURPOSE: The dose-limiting factor of ramucirumab plus docetaxel (RAM + DTX) in patients with non-small cell lung cancer (NSCLC) is febrile neutropenia (FN), which has a high incidence in Asians. This study aimed to evaluate the cost-effectiveness of pegfilgrastim (Peg-G) in patients with NSCLC receiving RAM + DTX in Japan. METHODS: We simulated model patients treated with RAM + DTX in Japan and developed a decision-analytical model for patients receiving Peg-G prophylaxis or no primary prophylaxis. The expected cost, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio (ICER) of each treatment were calculated from the perspective of a Japanese healthcare payer. The willingness-to-pay (WTP) threshold was set at 45,867 United States dollars (USD) (5 million Japanese yen) per QALY gained. The probabilities, utility values, and other costs were obtained from published sources. Deterministic sensitivity analysis (DSA) and probabilistic analysis were conducted to evaluate the effect of each parameter and robustness of the base-case results. RESULTS: The expected cost and QALYs were 20,275 USD and 0.701 for Peg-G prophylaxis and 17,493 USD and 0.672 for no primary prophylaxis, respectively. The ICER was calculated to be 97,519 USD per QALY gained. The results were most sensitive to FN risk with Peg-G. When FN risk with no primary prophylaxis exceeded 51% or the cost of Peg-G was less than 649 USD per injection, the ICER was below the WTP threshold. The probabilistic analysis revealed a 9.1% probability that the ICER was below the WTP threshold. CONCLUSION: Peg-G is not cost-effective in patients with NSCLC receiving RAM + DTX in Japan.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Expanded access to anticancer treatments from conversion to biosimilar pegfilgrastim-cbqv in US breast cancer patients.

Aim: To estimate cost-savings from conversion to biosimilar pegfilgrastim-cbqv that could be reallocated to provide budget-neutral expanded access to AC (doxorubicin/cyclophosphamide) and TCH (docetaxel/carboplatin/trastuzumab) in breast cancer (BC) patients. Methods: Simulation modeling in panels of 20,000 BC and 5000 HER2+ (HER2+ BC) patients, varying treatment duration (one-six cycles) and conversion rates (10-100%), to estimate cost-savings and additional AC and TCH treatment that could be provided. Results: In 20,000 patients, cost-savings of $1,083 per-patient per-cycle translate to $21,652,064 (one cycle) to $129,912,397 (six cycles). Savings range from $5,413,016 to $32,478,097, respectively, in the 5000-patient HER2+ BC panel. Conclusion: Conversion to pegfilgrastim-cbqv could save up to $130 million and provide more than 220,000 additional cycles of antineoplastic treatment on a budget-neutral basis to BC patients.

Lay abstract Pegfilgrastim is used to prevent low white blood cell count in patients receiving chemotherapy. Comparable to a generic version of a drug, a biosimilar is a follow-on version of a biologic treatment. We calculated the savings from using biosimilar pegfilgrastim in a hypothetical group of 20,000 patients with breast cancer receiving chemotherapy with AC (doxorubicin/cyclophosphamide). We then computed the number of additional doses of AC chemotherapy that could be purchased with those savings. We did the same for a group of 5000 HER2+ breast cancer patients treated with TCH (docetaxel/carboplatin/trastuzumab). Using biosimilar pegfilgrastim could save $1,083 per patient per cycle. If all patients were treated with biosimilar pegfilgrastim over six cycles, $129.9 million could be saved in the AC group and $32.5 million in the TCH group. This could provide 220,468 additional AC doses and 6981 TCH doses. Biosimilar pegfilgrastim can generate significant savings. These savings can be used to provide additional patients with chemotherapy cost-free.

A comparative multi-tiered immunogenicity assessment of biosimilar pegylated filgrastim: validation of methods for clinical assessment of INTP5.

BACKGROUND AND OBJECTIVE: Validated and highly sensitive assays are required for comparative assessment of immunogenicity of biosimilars. For INTP5, a biosimilar pegylated filgrastim, the immunogenicity assessment included tiers that allowed for assessment of antibodies against the PEG and the Filgrastim moieties for comparative clinical immunogenicity assessment. METHODS: Electrochemiluminescence immunoassay (ECLIA) was used for Screening, Specificity, and Titer assays for detecting anti-drug antibodies (ADAs) and cell-based method for neutralizing ADAs. The methods were validated to enable use of same methods irrespective of biosimilar or reference arms. RESULTS: The ADA and cell-based assay for neutralizing antibody detection were validated with a sensitivity capable of detecting binding Anti-Pegfilgrastim antibody at ~40 ng/mL and Neutralizing antibody at ~380 ng/mL and used for a comparative immunogenicity study. Of 194 subjects, 10 subjects had confirmed positive anti-drug-antibody in the biosimilar arm and 9 in the reference arm. None of the subjects were detected with neutralizing anti-drug antibodies. CONCLUSION: This work demonstrates the application of a rigorous approach toward validation of assays for immunogenicity studies for biosimilars. Highly sensitive, precise, and robust assays were used to conclude comparable low incidences of anti-drug antibodies in both biosimilar and innovator arms of the clinical study for Pegfilgrastim.

Efficacy and cost of G-CSF derivatives for prophylaxis of febrile neutropenia in lymphoma and multiple myeloma patients underwent autologous hematopoietic stem cell transplantation.

OBJECTIVES: To compare the efficacies and costs between pegfilgrastim and filgrastim prophylaxis for FN post-ASCT for lymphoma and multiple myeloma patients. METHODS: 43 patients who received pegfilgrastim (6 mg) were compared to a retrospective cohort of 129 patients that had received filgrastim post-ASCT. Hematopoietic recovery time, FN incidence and treatment costs were assessed and compared. RESULTS: The mean time to absolute neutrophil count engraftment was 8.72 ± 2.38 days for the prospective pegfilgrastim group and 9.87 ± 3.13 days for the retrospective filgrastim group (P = 0.027). The incidence of FN was 18.60% and 50.39% in prospective pegfilgrastim and retrospective filgrastim groups, respectively (P = 0.000). The mean cost of filgrastim was $617.22 ± 37.87, compared with $525.78 for pegfilgrastim (P = 0.032). DISCUSSION: Convenience, effectiveness, and safety of prophylaxis for FN in the prospective pegfilgrastim group were significantly improved compared to the retrospective filgrastim group in ASCT patients. CONCLUSION: Pegfilgrastim prophylaxis was more effective and convenient than filgrastim for FN prophylaxis in patients post-ASCT, especially for MM patients.

Cost-effectiveness of primary prophylaxis of febrile neutropenia with pegfilgrastim in docetaxel, cisplatin and 5-fluorouracil therapy for esophageal cancer.

Objective: The efficacy of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy in treating esophageal cancer has been reported. However, febrile neutropenia (FN) is a potentially serious adverse event of DCF therapy with an incidence of 10 to 40%. Pegfilgrastim, a granulocyte colony-stimulating factor (G-CSF), has been shown to have a primary prophylactic role in FN. However, it has been suggested that excessive use of expensive G-CSF should be avoided. Therefore, we performed a cost-utility analysis of primary prophylaxis with pegfilgrastim. Design: Cost-effectiveness analysis using decision tree modelling. Methods: We used a decision tree analysis model based on the report of primary prophylaxis with pegfilgrastim. Based on a previous study, the FN incidence rate was set at 40.0% (95% confidence interval (CI): 11.9-68.1) for the pegfilgrastim group and 43.5% (95%CI: 21.6-65.4) for the no pegfilgrastim group. The FN treatment cost was US$726.63, and the duration of FN was 3.65±1.20 days. The utility value of patients who received DCF therapy was 0.643, and the change in utility value at FN onset was -0.15. Expected cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) were calculated, and cost-utility analysis was performed. Results: The ICER of pegfilgrastim was 184,976.75 USD/QALY. As a result of sensitivity analysis, the utility of FN had the greatest impact on the cost-effectiveness analysis, followed by the drug cost of pegfilgrastim. Conclusion: Primary prophylaxis of FN with pegfilgrastim might not be cost-effectiveness. In determining whether to administer pegfilgrastim it is necessary to consider patient factors, not just the incidence of FN.