Cost Differences of Same-Day Vs Next-Day Use of Pegfilgrastim
Authors: Li Xiaoyan , Zhang Xinke , Lin Junji , Fust Kelly , Garcia Jacob 
Published: October 2019

Abstract
Introduction:Febrile neutropenia (FN) is a serious side effect of myelosuppressive chemotherapy that often requires immediate hospitalization. FN is associated with lengthy hospital stays, increased mortality, and high costs. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) such as pegfilgrastim can reduce risk of FN. Per indication, pegfilgrastim should not be administered between 14 days before and 24 hours after cytotoxic chemotherapy. In most clinical trials, G-CSF has been administered the day following chemotherapy, and administration 1-3 days after chemotherapy may result in a lower risk of infection than same-day administration (Burris et al, J Oncol Pract, 2010; Cheng et al, Anticancer Drugs, 2014; Weycker et al, J Clin Oncol, 2015 [abst e17697]). Thus, both NCCN and ASCO recommend pegfilgrastim be given 1-3 days after chemotherapy when possible. A recent retrospective analysis of US health care claims databases showed that same-day pegfilgrastim was used in 13% of cycles (Weycker et al, Blood, 2014). Here we compare the costs of same- vs next-day use of pegfilgrastim (Neulasta®) from a US payer perspective.
Methods: We used a published health economic model on the budget impact of G-CSFs to US payers (Taylor et al, Am J Pharm Benefits, 2012) to estimate differences in per-patient costs associated with same- vs next-day pegfilgrastim use among adult patients with early-stage breast cancer (ESBC) or NHL treated with 1 course (6 cycles) of myelosuppressive chemotherapy (TAC for ESBC; R-CHOP for NHL). Data from 2 phase 2 trials (Burris 2010) and 2 large retrospective studies (Weycker 2015; Cheng 2014) identified in a literature search for studies of FN risk with same- vs next-day use of pegfilgrastim in patients with ESBC or NHL were used to derive plausible ranges of estimated cost differences. Ranges were based on variability in the difference of FN risk between groups as reported in or estimated from these studies. The model assumed patients received prophylactic pegfilgrastim and 1 complete blood cell (CBC) count in each chemotherapy cycle. Percentage of FN events requiring hospitalization and costs associated with pegfilgrastim acquisition, administration, lab work, and FN treatment were derived from published literature and public data sources consistent with Taylor 2012. Chemotherapy costs were assumed to be independent of same- vs next-day pegfilgrastim use and were excluded. All costs are presented in 2015 US dollars.
Results: Costs for ESBC were $944 to $6,920 greater per patient per course of chemotherapy with same- vs next-day use of pegfilgrastim. Costs for NHL were $629 to $3,775 greater per patient per course of chemotherapy with same- vs next-day use of pegfilgrastim. See table.
Conclusions: This analysis suggests that adherence to next-day use of pegfilgrastim is associated with lower costs than same-day use. Cost differences appear to be driven by FN risk and FN treatment, indicating that these results can be reasonably extrapolated to other regimens with an intermediate/high risk of FN.
Table. Estimates of FN Risk and Per-Patient Costs Breast Cancer NHL Burris 2010 Weycker 2015 Burris 2010 Weycker 2015 Cheng 2014 Same Day Next Day Same Day Next Day Same Day Next Day Same Day Next Day Same Day Next Day FN risk (%) 33a 11a 10b 7c 17a 15a 19b 14c 26d 14d Pegfilgrastim acquisition $19,815 $19,815 $19,815 $19,815 $19,815 $19,815 $19,815 $19,815 $19,815 $19,815 Administration $333 $333 $333 $333 $333 $333 $333 $333 $333 $333 CBCs $423 $423 $423 $423 $423 $423 $423 $423 $423 $423 FN treatmente $10,380 $3,460 $3,145 $2,202 $5,347 $4,718 $5,976 $4,404 $8,178 $4,404 Total cost $30,951 $24,031 $23,716 $22,773 $25,918 $25,289 $26,547 $24,974 $28,749 $24,974 Cost differences (next- vs same-day use) (6,920) (944) (629) (1,573) (3,775) Values in parentheses indicate cost savings. a Estimates from Burris 2010; b Estimates from Taylor 2012 for next-day use (7% for TAC and 14% for R-CHOP) were multiplied by relative risk (TAC: 1.36; R-CHOP: 1.33), which was calculated from the cycle-level odds ratio (1.4) reported in Weycker 2015; c Estimates from Taylor 2012; d Estimates from Taylor 2012 for next-day use (14% for R-CHOP) were multiplied by relative risk (1.84), which was calculated from cycle-level results in Cheng 2014 (9.4% for same-day use and 5.1% for next-day use); e Based on current literature, we assumed that the likelihood that an FN event would require hospitalization was 80%.

Disclosures
Li: Amgen, Inc.: Employment, Equity Ownership. Off Label Use: This abstract describes costs associated with same-day administration of pegfilgrastim, which is an off label use of pegfilgrastim. As noted in the abstract text, "Per indication, pegfilgrastim should not be administered between 14 days before and 24 hours after cytotoxic chemotherapy.". Zhang:Amgen Inc.: Other: Internship. Lin:Amgen Inc.: Employment, Other: stock ownership. Fust:Optum: Employment; Amgen Inc.: Consultancy, Research Funding. Garcia:Amgen Inc: Employment, Equity Ownership.