Risk Of Chemotherapy-induced Febrile Neutropenia Research Articles

Risk of chemotherapy-induced febrile neutropenia in intermediate-risk regimens: Clinical and economic outcomes of granulocyte colony-stimulating factor prophylaxis.

BACKGROUND: Chemotherapy-induced neutropenia increases the risk of febrile neutropenia (FN) and infection with resultant hospitalizations, with substantial health care resource utilization (HCRU) and costs. Granulocyte-colony stimulating factor (GCSF) is recommended as primary prophylaxis for chemotherapy regimens having more than a 20% risk of FN. Yet, for intermediate-risk (10%-20%) regimens, it should be considered only for patients with 1 or more clinical risk factors (RFs) for FN. It is unclear whether FN prophylaxis for intermediate-risk patients is being optimally implemented. OBJECTIVE: To examine RFs, prophylaxis use, HCRU, and costs associated with incident FN during chemotherapy. METHODS: This retrospective study used administrative claims data for commercial and Medicare Advantage enrollees with nonmyeloid cancer treated with intermediate-risk chemotherapy regimens during January 1, 2009, to March 31, 2020. Clinical RFs, GCSF prophylaxis, incident FN, HCRU, and costs were analyzed descriptively by receipt of primary GCSF, secondary GCSF, or no GCSF prophylaxis. Multivariable Cox regression analysis was used to examine the association between number of RFs and cumulative FN risk. RESULTS: The sample comprised 13,937 patients (mean age 67 years, 55% female). Patients had a mean of 2.3 RFs, the most common being recent surgery, were aged 65 years or greater, and had baseline liver or renal dysfunction; 98% had 1 or more RFs. However, only 35% of patients received primary prophylaxis; 12% received secondary prophylaxis. The hazard ratio of incident FN was higher with increasing number of RFs during the first line of therapy, yet more than 54% of patients received no prophylaxis, regardless of RFs. Use of GCSF prophylaxis varied more by chemotherapeutic regimen than by number of RFs. Among patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone, 76% received primary prophylaxis, whereas only 22% of patients treated with carboplatin/paclitaxel received primary prophylaxis. Among patients with a first line of therapy FN event, 78% had an inpatient stay and 42% had an emergency visit. During cycle 1, mean FN-related coordination of benefits-adjusted medical costs per patient per month ($13,886 for patients with primary prophylaxis and $18,233 for those with none) were driven by inpatient hospitalizations, at 91% and 97%, respectively. CONCLUSIONS: Incident FN occurred more often with increasing numbers of RFs, but GCSF prophylaxis use did not rise correspondingly. Variation in prophylaxis use was greater based on regimen than RF number. Lower health care costs were observed among patients with primary prophylaxis use. Improved individual risk identification for intermediate-risk regimens and appropriate prophylaxis may decrease FN events toward the goal of better clinical and health care cost outcomes. DISCLOSURES: This work was funded by Sandoz Inc., which participated in the design of the study, interpretation of the data, writing and revision of the manuscript, and the decision to submit the manuscript for publication. The study was performed by Optum under contract with Sandoz Inc. The author(s) meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the manuscript. Dr Li is an employee of Sandoz Inc. Drs Bell and Lal and Mr Peterson-Brandt were employees of Optum at the time of the study. Ms Anderson and Dr Aslam are employees of Optum. Dr Lyman has been primary investigator on a research grant from Amgen to their institution and has consulted for Sandoz, G1 Therapeutics, Partners Healthcare, BeyondSpring, ER Squibb, Merck, Jazz Pharm, Kallyope, Teva; Fresenius Kabi, Seattle Genetics, and Samsung.

Budget Saving Potential of Pegfilgrastim Biosimilar for the Treatment of Chemotherapy-Induced Febrile Neutropenia, in Italy

INTRODUCTION: Current Italian guidelines recommend prophylaxis with granulocyte colony-stimulating factors (G-CSFs) to reduce the risk of chemotherapy-induced febrile neutropenia (FN). The availability of G-CSF biosimilars represents an opportunity for savings in the Italian National Healthcare Service (NHS) delivery of care.OBJECTIVE: To assess the cost saving potential associated with the introduction of pegfilgrastim biosimilars to local formularies, compared to the current G-CSF standard practice in Italy.METHODS: A budget impact model was developed to compare the current standard practice of long-acting (LA) and short-acting (SA) G-CSFs use, with a future scenario in which the market share of LA G-CSFs grows due to the more advantageous administration schedule and price of pegfilgrastim biosimilar. The analysis included G-CSF treatment schedules, drug acquisition costs and costs of patient management including hospitalization and ambulatory care.RESULTS: The introduction of pegfilgrastim biosimilar resulted in cumulative 3-year cost savings of € 59,650 and € 41,539 for FN prophylaxis in a potential cohort of 1000 patients with solid tumors and lymphomas, respectively.CONCLUSIONS: The results indicate that the introduction of pegfilgrastim biosimilar is potentially associated with substantial cost savings for the Italian healthcare system.

Myeloprotective Effects of Trilaciclib Among Patients with Small Cell Lung Cancer at Increased Risk of Chemotherapy-Induced Myelosuppression: Pooled Results from Three Phase 2, Randomized, Double-Blind, Placebo-Controlled Studies.

PurposeTrilaciclib is an intravenous cyclin-dependent kinase 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression (CIM) by protecting hematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myeloprotection). Here, we investigated the myeloprotective effects of trilaciclib among patients at increased risk of CIM.Patients and MethodsData were pooled from three randomized, double-blind, placebo-controlled, phase 2 clinical studies of trilaciclib administered prior to chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Myeloprotective outcomes were evaluated in patient subgroups based on age (<65 or ≥65 years), risk of chemotherapy-induced febrile neutropenia (FN), and risk of anemia or red blood cell (RBC) transfusions. For the FN and anemia analyses, risk factors were identified from published literature and used to classify patients into FN and anemia risk categories. Subgroup analysis based on age was also performed on patient reported outcome (PRO) measures.ResultsIn total, 123 patients received trilaciclib and 119 patients received placebo. Myeloprotective benefits of trilaciclib were observed regardless of age, with greater effects observed among patients aged ≥65 years. Across FN risk factors and categories, trilaciclib had beneficial effects on neutrophil-related endpoints vs placebo, with greater effects observed in patients at higher risk of FN. Effects on RBC-related endpoints favored trilaciclib vs placebo, regardless of anemia risk factors and categories. Improvements in PROs with trilaciclib were observed irrespective of age group, but with greater improvements and less deterioration from baseline observed in older patients.ConclusionBy both decreasing the incidence of CIM and improving quality of life, trilaciclib has the potential to allow patients receiving chemotherapy for ES-SCLC, including patients who are older or more vulnerable to CIM, to receive chemotherapy on schedule and at standard-of-care doses, and to improve the experience for patients receiving chemotherapy to treat ES-SCLC.Clinical Trial NumbersNCT02499770; NCT03041311; NCT02514447.

MO01.42 Myelopreservation with Trilaciclib Regardless of Risk of Chemotherapy-Induced Febrile Neutropenia and/or Anemia or Red Blood Cell Transfusions

MO01.42 Myelopreservation with Trilaciclib Regardless of Risk of Chemotherapy-Induced Febrile Neutropenia and/or Anemia or Red Blood Cell Transfusions

Risk of chemotherapy-induced febrile neutropenia in patients with metastatic cancer not receiving granulocyte colony-stimulating factor prophylaxis in US clinical practice

ObjectivesTo evaluate the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis in US patients with selected metastatic cancers and chemotherapy-induced febrile neutropenia (FN) incidence and associated outcomes among the subgroup who did not receive prophylaxis.MethodsThis retrospective cohort study was conducted at four US health systems and included adults with metastatic cancer (breast, colorectal, lung, non-Hodgkin lymphoma [NHL]) who received myelosuppressive chemotherapy (2009–2017). Patients were stratified by FN risk level based on risk factors and chemotherapy (low/unclassified risk, intermediate risk without any risk factors, intermediate risk with ≥ 1 risk factor [IR + 1], high risk [HR]). G-CSF use was evaluated among all patients stratified by FN risk, and FN/FN-related outcomes were evaluated among patients who did not receive first-cycle G-CSF prophylaxis.ResultsAmong 1457 metastatic cancer patients, 20.5% and 28.1% were classified as HR and IR + 1, respectively. First-cycle G-CSF prophylaxis use was 48.5% among HR patients and 13.9% among IR + 1 patients. In the subgroup not receiving first-cycle G-CSF prophylaxis, FN incidence in cycle 1 was 7.8% for HR patients and 4.8% for IR + 1 patients; during the course, corresponding values were 16.9% and 15.9%. Most (> 90%) FN episodes required hospitalization, and mortality risk ranged from 7.1 to 26.9% across subgroups.ConclusionIn this retrospective study, the majority of metastatic cancer chemotherapy patients for whom G-CSF prophylaxis is recommended did not receive it; FN incidence in this subgroup was notably high. Patients with elevated FN risk should be carefully identified and managed to ensure appropriate use of supportive care.

Abstract P2-08-24: Risk of chemotherapy-induced febrile neutropenia (FN) in patients with metastatic cancer of the breast or other sites not receiving colony-stimulating factor prophylaxis (CSF) in US clinical practice

Abstract Background: Clinical practice guidelines recommend CSF prophylaxis for patients receiving chemotherapy regimens with a high risk of FN (&amp;gt;20%), and consideration of CSF prophylaxis for those receiving intermediate-risk regimens (10-20%) who have ≥1 risk factor for FN. The objective of this study was to estimate the use of CSF prophylaxis among patients with metastatic cancer, and the risk of FN among eligible patients not receiving it. Methods: This retrospective study was conducted at four US health systems—Geisinger Health System (PA), Henry Ford Health System (MI), Kaiser Permanente Northwest (OR, WA), and Reliant Medical Group (MA). Study population comprised patients who received chemotherapy for metastatic solid tumors (breast, colon/rectum, lung) or non-Hodgkin’s lymphoma (NHL) from 2009-2017. For each eligible patient, data on chemotherapy course, cycles, and regimens, as well as the use of supportive care (CSF, antimicrobials) and FN episodes during the course, were collected via a standardized case report form using electronic data warehouses, cancer registries, and medical charts. Analyses were non-comparative and descriptive only. Results: Study population totaled 1,457 patients (26% breast; 25% colon/rectum; 43% lung; 6% NHL). Nearly half of all patients received a chemotherapy regimen classified as either high-risk for FN (21%), or intermediate-risk for FN and had ≥1 FN risk factor (28%). Among patients receiving high-risk regimens, 51% did not receive primary prophylaxis with CSF (PP-CSF), and among those receiving an intermediate-risk regimen with ≥1 risk factor, 86% did not receive PP-CSF; among all remaining patients, 89% did not receive PP-CSF. Across these three subgroups of patients who did not receive PP-CSF (ie, high-risk regimen, intermediate-risk regimen with ≥1 risk factor, all others), FN risk during the course was 17%, 16%, and 14%, respectively. More than 90% of FN episodes required hospitalization, and FN-related mortality was 14%. Among metastatic breast cancer patients, 56% received a high-risk regimen (46%) or an intermediate-risk regimen and had ≥1 FN risk factor (10%); among this subset, 30% did not receive PP-CSF and their FN risk was 16%. Conclusions: In this real-world evaluation of patients with metastatic cancer of the breast or other sites receiving chemotherapy at four large US health systems, over two-thirds of patients who were candidates for PP-CSF (per clinical guidelines) did not receive it. Among the subset of candidates who did not receive PP-CSF, FN risk was high (16%) and associated consequences were severe. Careful consideration should be given to identifying metastatic patients at elevated risk of FN—based on their chemotherapy regimen and risk factors—to ensure appropriate use of supportive care. Table. FN risk factors and chemotherapy FN risk level among metastatic patientsBreast Cancer (N = 380)Colorectal Cancer (N = 360)Lung Cancer (N = 626)NHL (N = 91)All (N = 1,457)FN Risk FactorsAge ≥65y, %20.821.137.240.729.2Prior chemotherapy or radiation therapy, %39.234.248.445.142.3Prior neutropenia, %1.82.22.69.92.7Bone marrow involvement, %27.12.830.024.222.2Recent surgery, %40.042.216.914.329.0Liver dysfunction (bilirubin &amp;gt;2.0), %0.81.40.50.00.8Renal dysfunction (creatinine clearance &amp;lt;50), %45.362.259.365.956.8Chemotherapy FN Risk Level, %High45.80.017.417.620.5Intermediate10.554.726.450.530.7Low8.922.541.20.025.6Unclassified34.722.815.031.923.1 Citation Format: Derek Weycker, Amanda Silvia, Ahuva Hanau, Lois Lamerato, Kathryn Richert-Boe, Manpreet Kaur, Neel Shah, Mark Hatfield, Gary H Lyman. Risk of chemotherapy-induced febrile neutropenia (FN) in patients with metastatic cancer of the breast or other sites not receiving colony-stimulating factor prophylaxis (CSF) in US clinical practice [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-24.

Cost Simulation for Febrile Neutropenia Hospitalization in the US Due to Pegfilgrastim on-Body Injector Failure Compared to Single-Injection Pegfilgrastim and Daily Injections with Reference and Biosimilar Filgrastim in Non-Hodgkin Lymphoma

Introduction: Failure rates ranging from 1.7-3.8% of the pegfilgrastim on-body injector (PEG-OBI) device have been reported (Joshi, Curr Med Res Opin 2017; Stuessy, J Clin Onc 2017; Mahler, Clin J Onc Nurs 2017). Failures may increase the risk of chemotherapy-induced febrile neutropenia (FN) and FN-related hospitalizations (FN-HOSP) beyond the FN and FN-HOSP rates for prophylaxis with single-injection pegfilgrastim (PEG) or daily injections of reference (REF-FIL) or Sandoz filgrastim biosimilar (BIOSIM-FIL). We aimed to estimate for a US panel of 10,000 patients with non-Hodgkin lymphoma (NHL) the total incremental costs of PEG-OBI prophylaxis and incremental FN-HOSP costs at different PEG-OBI failure rates versus (vs) assured prophylaxis administration with PEG, REF-FIL, or BIOSIM-FIL.Methods: Simulation analysis from a US payer perspective of the total incremental prophylaxis costs associated with PEG-OBI failure rates of 1-5% compared to assured prophylaxis administration with PEG, REF-FIL, and BIOSIM-FIL in chemotherapy cycle 1 for a panel of 10,000 NHL patients. Filgrastim daily injection regimens included real-world durations of 5 (Gascón, Support Care Cancer 2016) and 6.5 days (Weycker, Ann Pharmacother 2006) and standard 11 days, all clinician-administered. Differential base rates of FN-HOSP (rate of FN-HOSP without colony-stimulating factor [CSF] minus rate with CSF) in NHL patients was computed for two chemotherapy regimens: 1) cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) (Chrischilles, Cancer Control 2002; 13.25% with CSF, 23.28% without), and 2) CHOP or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (Osby, Blood 2003; 33.0% with CSF, 50.0% without). Costs (US$) were based on 1Q2018 average selling price for drugs and 2018 Current Procedural Terminology reimbursement for administration. FN-HOSP costs in 2012 of $25,676 per episode for NHL patients (Tai, J Oncol Pract 2017) were adjusted per the Consumer Price Index for Medical Care to $29,938.63 for 2018.Results: Table 1 (Chrischilles; CHOP) and Table 2 (Osby; CHOP/CNOP) present, for PEG-OBI failures rates of 0.01-0.05, the incremental number of patients at risk for FN-HOSP and associated incremental costs; and total incremental costs of PEG-OBI prophylaxis over the costs of assured prophylaxis administration with other CSFs in CTX cycle 1 for a panel of 10,000 NHL patients. Except for one scenario (savings of $72,916 at 0.1 failure rate due to the lower PEG-OBI administration costs), all scenarios showed incremental costs associated with PEG-OBI prophylaxis and failures of the PEG-OBI device (Tables 1 and 2). Per Chrischilles rates, in a panel of 10,000 NHL patients, incremental FN-HOSP costs due to PEG-OBI device failure ranged from $300,284 (at 0.01 failure rate) to $1,501,422 (at 0.05 failure rate). Total incremental costs of PEG-OBI over PEG ranged from $227,369 to $1,128,222. Total incremental costs of PEG-OBI over REF-FIL ranged from $6,794,984 to $28,859,922; and over BIOSIM-FIL from $19,004,984 to $34,409,922. Per the Osby rates, in a panel of 10,000 NHL patients, incremental FN-HOSP costs due to PEG-OBI device failure ranged from $508,957 to $2,544,784. Total incremental costs of PEG-OBI over PEG ranged from $135,757 to $2,171,584; over REF-FIL from $7,003,657 to $29,903,284; and over BIOSIM-FIL from $19,213,657 to $35,453,284.Conclusions: In this simulation of NHL patients treated with CHOP or CNOP, the total incremental costs of PEG-OBI prophylaxis vs assured prophylaxis administration with other CSFs vary as a function of PEG-OBI failure rates, baseline and failure-associated FN-HOSP risk, and the alternative CSF prophylaxis option. Incremental costs of PEG-OBI prophylaxis and failure are lowest vs PEG and highest vs BIOSIM-FIL at real-world duration of 5 days. [Display omitted] DisclosuresKrendyukov:Sandoz: Employment. Mathieson:Sandoz: Employment. Campbell:Sandoz Inc.: Employment. Balu:Sandoz Inc.: Employment. MacDonald:Sandoz: Consultancy. Abraham:Sandoz: Consultancy.

Risk of chemotherapy-induced febrile neutropenia with same-day versus next-day pegfilgrastim prophylaxis among patients aged ≥65 years: a retrospective evaluation using Medicare claims

Background: Two recent evaluations reported that risk of febrile neutropenia (FN) may be higher when pegfilgrastim prophylaxis (PP) is administered on same day as chemotherapy rather than per recommendation (1–3 days following chemotherapy). Such evidence is based largely on the experience of younger privately insured adults and may not be generalizable to older patients in US clinical practice.Methods: A retrospective cohort design and data from Medicare Claims Research Identifiable Files (January 2008–September 2015) were employed. Patients were aged ≥65 years, had breast cancer or non-Hodgkin’s lymphoma, received chemotherapy with intermediate/high risk for FN, and received PP in ≥1 cycle; cycles with PP were stratified based on administration day (same-day [“Day 0”] vs. 1–3 days following chemotherapy [“Days 1–3”]) and were pooled for analyses. Adjusted odds ratios (ORs) for FN during the cycle were estimated for patients who received PP on Day 0 versus Days 1–3.Results: Study population included 65,003 patients who received PP in 261,184 cycles; in 5% of cycles, patients received PP on Day 0. Incidence proportion for FN in cycle 1 was 11.4% for Day 0 versus 8.4% for Days 1–3; adjusted OR was 1.4 (p < .001). Incidence proportion for FN when considering all cycles was 7.7% for Day 0 and 6.0% for Days 1–3; adjusted OR was 1.3 (p < .001). Adjusted ORs when considering all cycles and only inpatient FN episodes (1.3, p < .001) and the narrow definition for FN (1.5, p < .001) were similar.Conclusions: Among Medicare patients receiving chemotherapy and PP in US clinical practice, PP was administered before the recommended timing in 5% of cycles and FN incidence was significantly higher in these cycles. Along with prior research, study findings support recently updated US practice guidelines indicating that PP should be administered the day after chemotherapy.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis based on real-world data from 2010 to 2015

Objective: Evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis (PP) continue to receive it in later cycles, and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Available evidence, however, may not be reflective of current clinical practice. We undertook an evaluation to estimate the odds of FN, beginning with second chemotherapy cycle, among patients who received PP in that cycle and all previous cycles versus those who received PP in all previous cycles only, using recent real-world data.Methods: A matched-cohort design and data from two US healthcare claims repositories (2010–2015) were employed. The source population comprised cancer patients who received intermediate/high-risk chemotherapy and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this subset, patients who did not receive PP in the cycle of interest (“comparison patients”) were matched to those who received PP in that cycle (“PP patients”); the same process was repeated for subsequent cycles. Odds ratios (ORs) for FN (broad and narrow definitions) were estimated using generalized estimating equations.Results: Among 47,254 patients in the source population, 9% did not receive second-cycle PP and were matched to those who did. FN odds in cycle 2 were significantly higher among comparison patients versus PP patients (OR [broad definition]: 1.7, p < .001); OR [narrow definition]: 4.3, p < .001). Results for subsequent cycles and for the last cycle, respectively, were comparable (OR [range, broad definition]: 1.6 to 3.1, p < .001 for all; OR [range, narrow definition]: 2.7 to 11.8, p < .001 for all).Conclusions: In this real-world evaluation of cancer chemotherapy patients who received first-cycle PP, FN risk was substantially higher among patients who did not receive PP in subsequent cycles versus those who continued PP.

Risk of chemotherapy-induced febrile neutropenia by day of pegfilgrastim prophylaxis in US clinical practice from 2010 to 2015

Objective: Pegfilgrastim prophylaxis (PP) is recommended 1–3 days following administration of chemotherapy during the cycle. Some patients, however, receive PP before or after the recommended timing. While evidence suggests that risk of febrile neutropenia (FN) may be lower when PP is administered per recommendation, such evidence is based on older data. We undertook a new study to compare FN risk between patients who received PP on the last day of chemotherapy (“day 0”) or 4–5 days following chemotherapy (“days 4–5”), versus 1–3 days following chemotherapy (“days 1–3”), using recent data from US clinical practice.Methods: A retrospective cohort design and data from two US private healthcare claims repositories (2010–2016) were employed. Patients received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin’s lymphoma, and PP in ≥1 cycle; all cycles with PP were pooled for analyses. Adjusted odds ratios (OR) for FN during the cycle were estimated for patients who received PP on day 0 or days 4–5, vs. days 1–3, using generalized estimating equations.Results: The study population included 53,814 patients who received PP in 217,273 cycles; in 9% of cycles, patients received PP on day 0 (8%) or days 4–5 (<1%). Odds of FN in cycle 1 were significantly higher among patients receiving PP on day 0 (OR: 1.4 [95% CI: 1.2–1.7]) or days 4–5 (1.9 [1.2–3.0]), vs. days 1–3, in that cycle. Results for subsequent cycles of chemotherapy were comparable to those for the first cycle.Conclusions: In this large-scale retrospective evaluation of cancer chemotherapy patients receiving PP in recent US clinical practice, PP was administered before or after the recommended timing in 9% of cycles. FN incidence was significantly higher in these cycles providing additional real-world evidence that PP should be administered the day after chemotherapy in alignment with recently updated US practice guidelines.

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's lymphoma patients under Taiwan's national health insurance system.

The beneficial effects of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy-induced febrile neutropenia (CIFN) were well documented throughout the literature. However, existing data regarding its cost-effectiveness were conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN under Taiwan's National Health Insurance (NHI) system. Data on clinical outcomes and direct medical costs were derived for 5179 newly diagnosed breast cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims database. Patients were further categorized into three subgroups as "primary-", "secondary-" and "no -" prophylaxis based on their patterns of G-CSF use. Generalized estimating equations were applied to estimate the impact of G-CSF use on the incidence of CIFN. The incremental cost-effectiveness ratios of primary and secondary prophylactic G-CSF use were calculated and sensitivity analyses were performed. Primary prophylaxis of G-CSF decreased the incidence of CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer and NHL patients, respectively. Compared with those with no prophylaxis, the incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among patients with breast cancer and NHL, respectively. In contrast, secondary prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer patients. Primary but not secondary prophylactic use of G-CSF was cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI system.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice.

PurposeAccumulating evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis continue to receive it in subsequent cycles and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Additional evidence from US clinical practice is warranted.MethodsData from two US private healthcare claims repositories were employed. The source population comprised adults who received “intermediate-risk” or “high-risk” chemotherapy regimens for solid cancers or non-Hodgkin’s lymphoma and first-cycle pegfilgrastim prophylaxis. From the source population, all patients who did not receive second-cycle pegfilgrastim prophylaxis ("comparison patients”) were matched (1:1) to those who received it (“pegfilgrastim patients”) based on cancer, regimen, and propensity score. Odds ratios (OR) for FN—broad and narrow definitions—during the second chemotherapy cycle were estimated for comparison patients versus pegfilgrastim patients using generalized estimating equations.ResultsA total of 2245 comparison patients (5.3 % of source population) were matched to pegfilgrastim patients; cohorts were well-balanced on baseline characteristics. Second-cycle FN incidence proportions for comparison and pegfilgrastim patients were 3.8 versus 2.2 % based on broad definition and 2.6 versus 0.8 % based on narrow definition; corresponding OR were 1.7 (95 % CI 1.2–2.5, p = 0.002) and 3.5 (95 % CI 2.0–6.0, p < 0.001). Results were similar within cancer/regimen-subgroups and were robust when using alternative methods for confounding adjustment.ConclusionsIn this retrospective evaluation of cancer chemotherapy patients who received first-cycle pegfilgrastim prophylaxis in US clinical practice, a clinically relevant minority did not receive second-cycle prophylaxis. Second-cycle FN odds among this subset were significantly higher than they were among those who continued prophylaxis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-015-3039-4) contains supplementary material, which is available to authorized users.

Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter?

PurposeContrary to the approved indication for pegfilgrastim prophylaxis, some patients receive it on the same day as the last administration of chemotherapy in clinical practice, which could adversely impact risk of febrile neutropenia (FN). An evaluation of the timing of pegfilgrastim prophylaxis and FN risk was undertaken.MethodsA retrospective cohort design and data from two US private health care claims repositories were employed. Study population comprised adults who received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin’s lymphoma (NHL) and received pegfilgrastim prophylaxis in ≥1 cycle; all cycles with pegfilgrastim were pooled for analyses. Odds ratios (OR) for FN during the cycle were estimated for patients who received pegfilgrastim on the same day (day 1) as the last administration of chemotherapy versus days 2–4 from chemotherapy completion.ResultsThe study population included 45,592 patients who received pegfilgrastim in 179,152 cycles (n = 37,095 in cycle 1); in 12 % of cycles, patients received pegfilgrastim on the same day as chemotherapy. Odds of FN were higher for patients receiving pegfilgrastim prophylaxis on the same day as chemotherapy versus days 2–4 from chemotherapy in cycle 1 (OR = 1.6, 95 % CI = 1.3–1.9, p < 0.001) and all cycles (OR = 1.5, 95 % CI = 1.3–1.6, p < 0.001).ConclusionsIn this large-scale evaluation of adults who received intermediate/high-risk regimens for solid tumors or NHL in US clinical practice, FN incidence was found to be significantly higher among those who received pegfilgrastim prophylaxis on the same day as chemotherapy completion versus days 2–4 from chemotherapy completion, underscoring the importance of adhering to the indicated administration schedule.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-015-3036-7) contains supplementary material, which is available to authorized users.

Risk of chemotherapy-induced febrile neutropenia (FN) with early discontinuation of pegfilgrastim prophylaxis (PEG-P) in U.S. clinical practice.

e17750 Background: Evidence suggests that not all cancer chemotherapy patients (pts) who receive first-cycle PEG-P continue to receive it in later cycles, and evidence from a recent clinical trial ...

Abstract P6-10-01: Risk of chemotherapy-induced febrile neutropenia (FN) in patients (pts) with non-metastatic breast cancer (BC) and documented risk factors for FN

Abstract Background: Clinical practice guidelines recommend primary prophylactic colony-stimulating factor (CSF) for pts with cancer receiving myelosuppressive chemotherapy when their risk of FN is high (≥20%). Evaluating FN risk in pts who receive regimens that are not documented as high risk in guidelines can be challenging; these pts may be at a high risk of developing FN based on a combination of regimen and pt risk factors. This retrospective study estimated FN risk among subgroups of pts with non-metastatic BC receiving 1 of 3 commonly used, non-high risk chemotherapy regimens. Methods: Pt-level data from 2 US healthcare claims databases comprising medical and outpatient pharmacy claims from commercial and Medicare supplemental plans were pooled. Eligible pts were ≥18 years old and had initiated a course of TC, TCH, or non-dose-dense AC/AC-T for non-metastatic BC between July 1, 2003 and June 30, 2012. Occurrence of FN during any cycle of the first chemotherapy course was identified using diagnosis codes for neutropenia, fever, or infection. Risk factors, documented in guidelines and the published literature, were evaluated during the 12 months before chemotherapy initiation. The percentage of pts, FN risk, and relative risk (RR, compared to pts with no risk factors) for subgroups of pts with specific risk factors are presented. Results: 50,893 pts were included in the analysis. FN risks by chemotherapy regimen and subgroup are shown in the table. TC N=26,266TCH N=9,105AC/AC-T N=15,522 % PtsFN Risk (RR, 95% CI)% PtsFN Risk (RR, 95% CI)% PtsFN Risk (RR, 95% CI)Any risk factor78.114.2 (1.4, 1.3-1.5)74.516.9 (1.3, 1.2-1.5)73.616.6 (1.6, 1.4-1.7)Age ≥6515.116.3 (1.6, 1.4-1.7)11.516.3 (1.3, 1.1-1.5)11.417.9 (1.7, 1.5-1.9)Chronic comorbidities Cardiovascular disease16.816.9 (1.6, 1.5-1.8)14.620.2 (1.6, 1.4-1.8)16.619.5 (1.8, 1.6-2.1)Diabetes11.817.4 (1.7, 1.5-1.9)10.221.3 (1.7, 1.4-2.0)11.120.4 (1.9, 1.7-2.2)Liver disease1.918.7 (1.8, 1.5-2.2)2.220.8 (1.6, 1.2-2.2)2.017.8 (1.7, 1.3-2.2)Lung disease2.023.4 (2.3, 1.9-2.7)1.530.7 (2.4, 1.8-3.2)1.927.1 (2.6, 2.1-3.2)Renal disease1.322.7 (2.2, 1.8-2.7)0.925.0 (2.0, 1.3-2.9)1.026.8 (2.5, 1.9-3.3)Osteoarthritis7.019.6 (1.9, 1.7-2.1)6.121.1 (1.7, 1.4-2.0)6.020.8 (2.0, 1.7-2.3)Thyroid disorder13.015.4 (1.5, 1.3-1.7)11.917.4 (1.4, 1.2-1.6)10.617.2 (1.6, 1.4-1.9)Number of risk factors 133.211.7 (1.1, 1.0-1.2)33.914.1 (1.1, 1.0-1.3)33.714.2 (1.3, 1.2-1.5)224.613.8 (1.3, 1.2-1.5)23.217.4 (1.4, 1.2-1.6)22.916.0 (1.5, 1.3-1.7)312.516.3 (1.6, 1.4-1.8)11.219.8 (1.6, 1.3-1.8)11.121.3 (2.0, 1.8-2.3)4+7.822.8 (2.2, 2.0-2.5)6.125.0 (2.0, 1.6-2.3)5.924.8 (2.3, 2.0-2.7)Reference group (0 risk factor)21.910.4 (NA)25.512.7 (NA)26.411.6 (NA)Selected risk factors are presented. A high proportion of pts (74%-78%) had ≥1 risk factor for FN, and these pts had a higher FN risk than pts with no risk factors. 55.4%, 56.7%, and 42.2% of all pts who received TC, TCH, or AC/AC-T, respectively, received CSF prophylaxis in cycle 1. Conclusions: FN risk assessments are needed for pts who are receiving non-high risk regimens. Citation Format: Derek Weycker, Xiaoyan Li, Richard Barron, Hongsheng Wu, Phuong Khanh Morrow, Hairong Xu, Maureen Reiner, Jacob Garcia, Shivani Mhatre, Gary Lyman. Risk of chemotherapy-induced febrile neutropenia (FN) in patients (pts) with non-metastatic breast cancer (BC) and documented risk factors for FN [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-10-01.

A prospectively validated nomogram for predicting the risk of chemotherapy-induced febrile neutropenia: a multicenter study.

There is clinical need to predict risk of febrile neutropenia before a specific cycle of chemotherapy in cancer patients. Data on 3882 chemotherapy cycles in 1089 consecutive patients with lung, breast, and colon cancer from four teaching hospitals were used to construct a predictive model for febrile neutropenia. A final nomogram derived from the multivariate predictive model was prospectively confirmed in a second cohort of 960 consecutive cases and 1444 cycles. The following factors were used to construct the nomogram: previous history of febrile neutropenia, pre-cycle lymphocyte count, type of cancer, cycle of current chemotherapy, and patient age. The predictive model had a concordance index of 0.95 (95 % confidence interval (CI) = 0.91-0.99) in the derivation cohort and 0.85 (95 % CI = 0.80-0.91) in the external validation cohort. A threshold of 15 % for the risk of febrile neutropenia in the derivation cohort was associated with a sensitivity of 0.76 and specificity of 0.98. These figures were 1.00 and 0.49 in the validation cohort if a risk threshold of 50 % was chosen. This nomogram is helpful in the prediction of febrile neutropenia after chemotherapy in patients with lung, breast, and colon cancer. Usage of this nomogram may help decrease the morbidity and mortality associated with febrile neutropenia and deserves further validation.

History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis.

Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.

Mannose-binding lectin (MBL) serum level and genotype and risk of chemotherapy-induced febrile neutropenia (FN) in patients with solid tumors.

e20653 Background: MBL is part of the innate immune system and deficiency in serum-MBL is in theory associated with an increase in infections during chemotherapy, although the exact cut-off levels ...

History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in patients with non-Hodgkin lymphoma not receiving granulocyte colony-stimulating factor prophylaxis

We conducted a cohort study to examine the association between a wide variety of chronic comorbidities and risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma (NHL) from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California. History of comorbidities and FN events were identified using electronic medical records. Cox model adjusting for propensity score was used to determine the association between a comorbid condition and FN. Models that additionally adjusted for cancer stage, baseline absolute neutrophil count, chemotherapy regimen and dose reduction were also evaluated. A total of 2480 patients with NHL were included, and 60% received CHOP/R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone, with or without rituximab). In total, 236 (9.5%) patients developed FN in the first chemotherapy cycle. Anemia (adjusted hazard ratio [HR] = 1.6, 95% confidence interval [1.2–2.2]), HIV infection (HR = 3.8 [2.0–6.7]) and rheumatoid diseases (HR = 2.4 [1.3–4.0]) were associated with significantly increased risk of FN. These results provide evidence that chronic comorbidity increases the risk of FN.

Discrete Choice Experiment to Estimate Breast Cancer Patients’ Preferences and Willingness to Pay for Prophylactic Granulocyte Colony-Stimulating Factors

ObjectivesRising out-of-pocket costs for cancer patients have increased shared decision making. Clinical guidelines recommend prophylactic granulocyte colony-stimulating factor (G-CSF) for patients receiving chemotherapy with a 20% or greater risk of febrile neutropenia. A discrete choice experiment was conducted to explore breast cancer patients’ preferences and willingness to pay (WTP) for prophylactic G-CSF to decrease the risk of chemotherapy-induced febrile neutropenia. MethodsAn online discrete choice experiment questionnaire survey of a national US convenience sample of self-reported breast cancer patients with prior chemotherapy treatment was conducted. Sixteen paired G-CSF treatment scenarios, each with four attributes (risk of disruption to chemotherapy schedule due to low white blood cell counts, risk of developing an infection requiring hospitalization, frequency of administration, and total out-of-pocket cost) were presented with a follow-up “no treatment” option. Participant preferences and WTP out of pocket were estimated by logistic regression. ResultsParticipants (n = 296) preferred G-CSF regimens with lower out-of-pocket costs, lower risk of chemotherapy disruption, lower risk of infection, and greater convenience (one G-CSF injection per chemotherapy cycle). Participants’ WTP was $1076 out of pocket per cycle to reduce the risk (high to low) of disrupting their chemotherapy schedule, $884 per cycle to reduce the risk (24% [high] to 7% [low]) of infection, and $851 per cycle to decrease the number of G-CSF injections (11 to 1) per cycle. ConclusionsParticipants highly valued specific features of prophylactic G-CSF treatment including maintaining their chemotherapy schedule, lowering their risk of infection, and reducing the number of injections. Physicians should consider patient preferences to inform the best treatment choices for individual patients.