Cost-effectiveness analysis of granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced febrile neutropenia in patients with breast cancer in Taiwan.

OBJECTIVES: To examine the cost-effectiveness of using granulocyte colony-stimulating factor (G-CSF) for primary or secondary prophylaxis in patients with breast cancer from the perspective of Taiwan's National Health Insurance Administration. METHODS: A Markov model was constructed to simulate the events that may occur during and after a high-risk chemotherapy treatment. Various G-CSF prophylaxis strategies and medications were compared in the model. Effectiveness data were derived from the literature and an analysis of the National Health Insurance Research Database (NHIRD). Cost data were obtained from a published NHIRD study, and health utility values were also obtained from the literature. Sensitivity analyses were performed to assess the uncertainty of the cost-effectiveness results. RESULTS: In the base-case analysis, primary prophylaxis with pegfilgrastim had an incremental cost-effectiveness ratio (ICER) of NT$269,683 per quality-adjusted life year (QALY) gained compared to primary prophylaxis with lenograstim. The ICER for primary prophylaxis with lenograstim versus no G-CSF prophylaxis was NT$61,995 per QALY gained. The results were most sensitive to variations in relative risk of febrile neutropenia (FN) for pegfilgrastim versus no G-CSF prophylaxis. Furthermore, in the probabilistic sensitivity analysis, at a willingness-to-pay threshold of one times Taiwan's gross domestic product per capita, the probability of being cost-effective was 88.1% for primary prophylaxis with pegfilgrastim. CONCLUSIONS: Our study suggests that primary prophylaxis with either short- or long-acting G-CSF could be considered cost-effective for FN prevention in breast cancer patients receiving high-risk regimens.

Chemotherapy-induced febrile neutropenia (FN): healthcare resource utilization (HCRU) and costs in commercially insured patients in the US.

PURPOSE: Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data. METHODS: A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group. RESULTS: 7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851). CONCLUSIONS: FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.

Febrile neutropenia-related care and associated costs in elderly patients with breast cancer, lung cancer, or non-Hodgkin lymphoma.

PURPOSE: Limited information is available regarding elderly patients experiencing febrile neutropenia (FN). This study evaluated FN-related care among elderly cancer patients who received high/intermediate FN-risk chemotherapy and experienced ≥ 1 FN episodes. METHODS: We used Medicare data to identify patients aged ≥ 66 years who initiated high/intermediate FN-risk chemotherapy between 1 January 2008 and 31 August 2015 to treat breast cancer (BC), lung cancer (LC), or non-Hodgkin lymphoma (NHL) and had ≥ 1 FN episodes. We identified within-cycle FN episodes for each chemotherapy cycle on Part A inpatient claims or outpatient or Part B claims. We described the FN-related care setting (inpatient hospital, outpatient emergency department [ED], or outpatient non-ED) and reported mean total cost of FN-related care per episode overall and by care setting (adjusted to 2015 US$). RESULTS: We identified 2138, 3521, and 2862 patients with BC, LC, and NHL, respectively, with ≥ 1 FN episodes (total episodes: 2407, 3840, 3587, respectively). Most FN episodes required inpatient care (BC, 88.1%; LC, 93.0%; NHL, 93.2%) with mean hospital length of stay (LOS) 6.2, 6.5, and 6.8 days, respectively. Intensive care unit admission was required for 20.4% of BC, 29.0% of LC, and 25.7% of NHL hospitalizations (mean LOS: 4.7, 4.7, 5.5 days, respectively). The mean total cost of FN care per episode was $11,959 BC, $14,388 LC, and $15,006 NHL, with inpatient admission the costliest care component ($11,826; $14,294; and $14,873; respectively). CONCLUSIONS: Among elderly patients with BC, LC, or NHL who experienced FN, most FN episodes required costly hospital care, highlighting the FN burden on healthcare systems.

Clinical Outcomes of Treatment with Filgrastim Versus a Filgrastim Biosimilar and Febrile Neutropenia-Associated Costs Among Patients with Nonmyeloid Cancer Undergoing Chemotherapy.

BACKGROUND: Granulocyte colony-stimulating factors such as filgrastim are used to decrease the incidence of febrile neutropenia (FN) among patients with nonmyeloid cancers undergoing chemotherapy treatment. Although the biosimilar filgrastim-sndz has been approved in the United States since 2015, limited real-world comparisons of filgrastim-sndz versus reference filgrastim (filgrastim-ref) have been conducted. OBJECTIVE: To compare FN incidence and assess overall FN-related health care resource utilization and medical costs among U.S. patients with non-myeloid cancer who received filgrastim-sndz or filgrastim-ref during their first chemotherapy cycle. METHODS: This was a retrospective claims analysis of patients with non-myeloid cancer who were enrolled in commercial or Medicare Advantage insurance plans from March 2015 through June 2016 and received filgrastim-sndz or filgrastim-ref during their first observed chemotherapy cycle. Patients with evidence of hematopoietic stem cell transplantation or pregnancy and those with missing demographic information were excluded. FN was defined on the basis of diagnosis codes for neutropenia and fever (N/F); neutropenia and infection (N/I); and neutropenia, infection, and fever (N/I/F). Cohorts were adjusted for differences in baseline patient characteristics using the inverse probability of treatment weighting (IPTW) method, and equivalence testing was used to compare the proportion of patients who developed FN between weighted cohorts. On the basis of the range of neutropenic fever incidence found in the PIONEER clinical trial, FN incidence was considered equivalent if 90% CIs for between-cohort differences were within ± 6%. Mean FN-related health care resource utilization and total FN-related medical costs were calculated for the overall study population. RESULTS: A total of 3,542 patients were included in the study (172 filgrastim-sndz; 3,370 filgrastim-ref; mean ages 62.1 years and 64.7 years, respectively). After IPTW, there were 162 patients in the filgrastim-sndz cohort and 3,297 in the filgrastim-ref cohort (mean age 64.5 years for both). FN incidence in the weighted filgrastim-sndz versus filgrastim-ref cohorts, respectively, was 1.4% versus 0.9% for N/F, 2.3% versus 1.7% for N/I, and 0.0% versus 0.3% for N/I/F; FN incidence was statistically equivalent between treatment cohorts. Among patients in either treatment cohort who developed FN, the proportion with FN-related inpatient stays during the first chemotherapy cycle ranged from 35.0% for N/I to 70.0% for N/I/F. Mean (SD) FN-related total medical costs across all patients who developed FN were $11,977 ($18,383) for N/F, $8,040 ($14,809) for N/I, and $21,733 ($30,003) for N/I/F, in 2015 U.S. dollars. For all 3 definitions of FN, the largest proportions (73.5%-93.4%) of medical costs were inpatient related. CONCLUSIONS: In this real-world study of patients with nonmyeloid cancers undergoing chemotherapy, the incidence of FN was statistically equivalent between individuals treated with filgrastim-sndz versus filgrastim-ref during their first chemotherapy cycle. FN-related health care resource utilization and medical costs among patients who developed FN were substantial. DISCLOSURES: This work was funded by Sandoz, which participated in the study design, data interpretation, writing and revision of the manuscript, and decision to submit the manuscript for publication. Balu and Campbell are employees of Sandoz, which is the manufacturer of the filgrastim biosimilars Zarzio and Zarxio. DeLeon was an employee of Sandoz at the time this study was conducted. Lal, Brekke, Elliott, and Korrer are employees of Optum, which was contracted by Sandoz to conduct this study.

Cutting costs and standardizing care: Once-per-cycle complete blood count monitoring may be safe for patients undergoing platinum-based chemotherapy.

AIM: The aim of this study was to evaluate whether frequency of complete blood count (CBC) testing during chemotherapy for gynecologic cancer impacts hospital admissions or rates of neutropenic fever. METHODS: A retrospective cohort study was performed at a single academic institution. Patients undergoing platinum-based chemotherapy for endometrial or ovarian cancer from January 2010 to December 2014 were identified from a clinical database. Patients receiving dose-dense chemotherapy or on a clinical trial were excluded. Electronic chart review collected demographic and clinical characteristics. The primary outcome was the rate of febrile neutropenia or hospital admission. RESULTS: A total of 174 patients were identified, 63 (36%) with endometrial and 111 (64%) with ovarian cancer. Fifty-four percent of patients received multiple CBC per cycle compared with 46% who only had one CBC per cycle. The majority of patients were treated with a platinum-based doublet (85%). Dose reductions, addition of granulocyte colony stimulating factor, and rates of grade 3 or 4 anemia and neutropenia were significantly associated with more frequent testing. There was no difference in rates of neutropenic fever (5.3 vs 3.8%, P = 0.45) or hospital admission (22.3 vs 21.3%, P = 0.86) for multiple versus single CBC monitoring. CONCLUSION: More frequent laboratory testing detected more cases of grade 3 or 4 hematopoietic toxicities and was associated with more interventions. There were no differences in number of hospitalizations or cases of neutropenic fever by frequency of laboratory testing, suggesting that it may be appropriate to decrease routine laboratory tests for select patients.

Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

PURPOSE: Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. METHODS: We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. RESULTS: Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. CONCLUSIONS: Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

Estimating the social value of G-CSF therapies in the United States.

OBJECTIVES: To provide a comprehensive estimate of the total social value (TSV) delivered by granulocyte-colony stimulating factor (G-CSF) therapies in the United States in 2014. STUDY DESIGN: Estimation of the TSV of G-CSF, based on a targeted literature review of pivotal studies. METHODS: A literature review was conducted to obtain estimates of the adverse outcomes associated with myelosuppressive chemotherapy-induced febrile neutropenia (FN) and the positive impacts of G-CSFs. We monetized each outcome into a set of mutually exclusive value components that were aggregated to estimate the TSV. To estimate the share of TSV captured by manufacturers, we estimated 2014 profits from G-CSF using measures of industry revenues and operating costs. RESULTS: In 2014, approximately 314,440 patients received G-CSFs. Compared with what they would have experienced without G-CSFs, these patients were less likely to be hospitalized or die from FN, incur reductions in chemotherapy relative dose intensity, receive antibiotics, miss work, or experience reduced health-related quality of life. We estimated the social value from fewer FN hospitalizations to be $770 million; from fewer FN-related deaths, $2.65 billion; from fewer deaths due to higher effective chemotherapy doses, $4.83 billion; from reductions in antibiotics, $2.3 million; from reductions in indirect costs, $230 million; and from improvements in health-related quality of life, $1.9 million. The estimated 2014 US TSV of G-CSFs was $8.5 billion. Industry profits associated with G-CSFs were estimated at $1.3 billion, accounting for approximately 15% of the TSV. CONCLUSIONS: Based on our calculations, the TSV generated by G-CSFs in the United States in 2014 was substantial, with the majority of this value accruing to patients.

Mortality, length of stay, and health care costs of febrile neutropenia-related hospitalizations among patients with breast cancer in the United States.

PURPOSE: Febrile neutropenia is a potentially life threatening complication of breast cancer chemotherapy associated with a significant amount of morbidity, mortality, and health care resource utilization. Recent data on the national estimates of mortality rate, length of stay, and health care costs among the subpopulation of febrile neutropenia admissions with breast cancer are lacking. METHODS: We used the Nationwide Inpatient Sample database to identify patients with breast cancer hospitalized for febrile neutropenia from 2009 to 2011. We derived data on inhospital mortality rate, length of stay, and mean health care costs and compared it with previous studies. RESULTS: The average inhospital mortality rate during 2009-2011 was 2.6 % (n = 685). Advanced age (≥ 65 years) was found to be significantly associated with a higher odds of mortality (4.4 vs 1.7 %, OR 2.7, 95 % CI 2.3-3.1, p < 0.01). The mean length of stay was 5.7 days (95 % CI 5.5-5.9 days), whereas the mean cost of hospitalization was $37,087 (95 % CI $34,009-$40,165). CONCLUSION: Febrile neutropenia-related hospitalizations continue to account for significant morbidity, mortality, and health care resource utilization among patients with breast cancer. Further efforts should be focused on curtailing the rising health care costs without compromising the quality of care.

Economic burden of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review.

The primary objective of this review was to identify the cost components that were most frequently associated with the economic burden of febrile neutropenia (FN) among patients with lymphoma. The secondary objective was to identify any parameter associated with higher FN cost. Ten cost of illness (COI) studies were identified. General characteristics on study design, country, perspective, and patient population were extracted and systematically reported. It was observed that majority (70%) of the studies employed the perspective of healthcare provider. 20% of the studies considered long-term costs. Estimated costs were adjusted to 2013 US dollars and ranged from US$5819 to US$34,756. The cost components that were most frequently associated with economic burden were ward and medication costs. Inpatient management, male gender, discharged dead, and comorbidity were positively associated with higher FN costs. Future COI studies on FN should focus on the accurate estimation on ward and medication costs.

Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors.

PURPOSE: Although studies have evaluated the risk and consequences of febrile neutropenia (FN) among patients receiving cancer chemotherapy in US clinical practice, none have focused on a broad group of patients with metastatic disease. METHODS: A retrospective cohort design and health care claims (2006 to 2011) from private health plans covering a geographically diverse US population of > 30 million persons annually were used. The study population included adults who underwent myelosuppressive chemotherapy for metastatic cancer of the breast (MBC), colon/rectum (MCRC), lung (MLC), ovaries (MOC), or prostate (MPC). For each patient, the first chemotherapy course and each cycle therein, along with each episode of FN and the consequences thereof, were identified. RESULTS: The most common regimens, by cancer type, were paclitaxel (18% of 15,318 patients with MBC); oxaliplatin, fluorouracil, and leucovorin (23% of 16,923 patients with MCRC); carboplatin plus paclitaxel (23% of 21,999 patients with MLC); carboplatin plus paclitaxel (49% of 7,433 patients with MOC); and docetaxel (68% of 4,667 patients with MPC). Across cancers, FN occurred in 13.1% to 20.6% of patients during their chemotherapy course, most often required hospitalization (89% to 94%), and most often occurred in the first cycle (23% to 36%). Among hospitalized patients with FN, mean length of stay ranged from 7.0 to 7.5 days, and inpatient mortality ranged from 3.9% to 10.3%; mean FN-related costs during the cycle ranged from $16,291 to $19,456. CONCLUSION: Among patients receiving myelosuppressive chemotherapy for metastatic cancer in US clinical practice, FN is a frequent complication, associated with significant morbidity, mortality, and economic costs, and should be given careful consideration in the treatment of this population.

The cost of the inpatient management of febrile neutropenia in cancer patients--a micro-costing study in the Irish healthcare setting.

The objective was to evaluate the resource use and cost of hospitalisation for febrile neutropenia (FN) from the health-payer's perspective. This was a single centre study. Adults undergoing chemotherapy, who were admitted for FN, were identified prospectively. Patient medical records were reviewed retrospectively. Demographics and resource utilisation data were obtained from a cohort of 32 patients (69% female, mean age = 58.8 years). Twenty-five per cent of patients had more than one FN episode. In total, 42 FN episodes were captured; 60% of episodes had occurred within the first two cycles of chemotherapy. The bootstrap estimation was used to determine mean hospital length of stay (LOS) with standard deviation (±SD) and mean costs ± SD. The mean LOS was 7.3 ± 0.5 days. The mean cost per FN episode was €8915 ± 718. The major cost driver was hospital bed-stay (mean cost of €6851 ± 549). Other cost drivers included antibacterial treatment at €760 ± 156, laboratory investigations at €538 ± 47 and the requirement for blood bank products at €525 ± 189. To our knowledge, this is the first investigation of the cost of chemotherapy induced FN within the context of the Irish healthcare setting.

Prospective multi-center study for quantification of chemotherapies and CTX-related direct medication costs avoided by use of biomarkers uPA and PAI-1 in primary breast cancer.

Biomarkers uPA/PAI-1 as recommended by ASCO and AGO are used in primary breast cancer to avoid unnecessary CTX in medium risk-recurrence patients. This study verified how many CTX cycles and CTX-related direct medication costs can be avoided by uPA/PAI-1 testing. A prospective, non-interventional, multi-center study was performed among six Certified Breast Centers to analyze application of uPA/PAI-1 and consecutive decision-making. CTX avoided were identified and direct costs for CTX, CTX-related concomitant medication and febrile neutropenia (FN) prophylaxis with G-CSF calculated. In n = 93 breast cancers n = 35 CTX (37.6%) with 210 CTX cycles were avoided according to uPA/PAI-1 test result. uPA/PAI-1 testing saved direct medication costs for CTX of 177,453 €, CTX-related concomitant medication of 27,482 € and FN prophylaxis of 20,599 €, overall 225,534 €. At test costs at 287.50 € uPA/PAI-1 testing resulted in additional costs of 26,737.50 €. uPA/PAI-1 has proven to be cost-effective at a return-on-investment ratio of 8.4:1. Indirect cost savings further increase this ROI. These results support decision-making for cost-effective diagnostics and therapy in breast cancer.

Mortality, length of stay, and cost associated with hospitalized adult cancer patients with febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) is a serious complication following chemotherapy and is associated with significant mortality and financial expenditure. The aim of this study was to evaluate risk factors for longer length of stay (LOS) and mortality and cost of treatment among hospitalized adults with cancer who developed febrile neutropenia in Thailand. MATERIALS AND METHODS: Information on illness of inpatients and casualties came from hospitals nationwide and from hospital withdrawals from the 3 health insurance schemes in fiscal 2010. The data covered 96% of the population and were analyzed by age groups, hospital level, and insurance year schemes in patients with febrile neutropenia. RESULTS: A total of 5,809 patients were identified in the study. The mortality rate was 14%. The median LOS was 8.67 days and 69% of patients stayed for longer than 5 days. On bivariate analysis, age, cancer type, and infectious complications (bacteremia/sepsis, hypotension, fungal infections, and pneumonia) were significantly associated with longer LOS and death. On multivariate analysis, acute leukemia and infectious complications were linked with longer LOS and death significantly. The median cost of hospitalized FN was THB 33,686 (USD 1,122) with the highest cost observed in acute leukemia patients. CONCLUSIONS: FN in adult patients results in significant mortality in hospitalized Thai patients. Factors associated with increased mortality include older age (>70), acute leukemia, comorbidity, and infectious complications.