Risk Factors For Febrile Neutropenia Research Articles

Overuse and underuse of pegfilgrastim for primary prophylaxis of febrile neutropenia.

Guidelines recommend pegfilgrastim for primary prophylaxis of febrile neutropenia after highly myelosuppressive chemotherapy. While deviations from guidelines could result in overuse and increased costs, underuse is also a concern and could compromise quality of care. Our objectives were to evaluate guideline adherence and quantify the extent to which physician heterogeneity may influence pegfilgrastim use. We randomly sampled 550 patients from a retrospective cohort of those who received infusions at an academic cancer center between 1 September 2013 and 1 September 2014. Electronic medical and drug dispensing records provided information on patient characteristics, chemotherapy characteristics, prescribing physician, and pegfilgrastim administration. We included 154 patients treated by 25 physicians. About half of patients were male and mean age was 61.3 years. Forty (26.1%) patients had no febrile neutropenia risk factors, 62 (40.5%) had one, and 51 (33.3%) had two or more. Thirty patients (19.5%) received pegfilgrastim, of which 12 (40%) received palliative chemotherapy. Nine (60%) of 15 patients on a regimen with a febrile neutropenia risk ≥ 20% received pegfilgrastim. Pegfilgrastim use significantly varied by cancer type (p < 0.01), chemotherapy regimen (p < 0.001), and regimen febrile neutropenia risk (p < 0.001). Multivariable analysis reaffirmed the association between chemotherapy regimen febrile neutropenia risk ≥ 20% and pegfilgrastim use (odds ratio (OR) = 10.1, 95% confidence interval (CI): 1.6-62.7) and suggested that 31% (95% CI: 8%-71%) of the variation in use was attributable to physician characteristics. Pegfilgrastim was potentially overused for palliative chemotherapy and underused for chemotherapy regimens with febrile neutropenia risk ≥ 20%. Successful interventions to modify prescribing practices likely require an understanding of the relationship between specific physician characteristics and pegfilgrastim use.

Value of incorporating newly identified risk factors into risk prediction for chemotherapy-induced febrile neutropenia.

Several comorbidities have recently been shown to affect risk of chemotherapy‐induced febrile neutropenia (FN). Here, we evaluated the added predictive value of these comorbidities beyond established FN risk factors. A retrospective cohort study was conducted among adult patients diagnosed with cancer and treated with chemotherapy at Kaiser Permanente Southern California between 2000 and 2009. The study cohort was equally split into training and validation datasets to develop and evaluate the performance of FN risk prediction models in the first chemotherapy cycle. A reference model was developed based on the model proposed by Lyman et al (Cancer 2011;117:1917). A new model was developed by incorporating the newly identified comorbidities such as rheumatoid conditions and thyroid disorders into the reference model. Area under the receiver operating characteristic curve (AUROCC), risk reclassification, and integrated discrimination improvement (IDI) were used to evaluate the potential improvement of FN risk prediction by incorporating comorbidities. A total of 15 279 patients were included; 4.2% experienced FN in the first chemotherapy cycle. Including comorbidities in FN risk prediction did not improve AUROCC (reference model 0.71 vs new model 0.72). A significant improvement in individual‐level FN risk prediction was indicated by IDI (P = .02). However, significant improvement in risk reclassification was not observed overall (although 6% of all patients were more accurately classified for their FN risk level, 5% were less accurately classified) or when examining predicted FN risk among patients who did and did not develop FN. Incorporating several new comorbidities into FN prediction led to improved FN risk prediction in the first chemotherapy cycle, although the observed improvements were small and might not be clinically relevant.

Febrile neutropenia in adjuvant and neoadjuvant chemotherapy for breast cancer: a retrospective study in routine clinical practice from a single institution.

Febrile neutropenia (FN) is one of the most common and most critical adverse effects of chemotherapy. Despite many existing guidelines based on the use of granulocyte-colony stimulating factor (G-CSF), FN continues to impair the quality of life and interfere with the treatment of many patients. The purpose of this study was to assess the incidence and management of FN associated with chemotherapy for early breast cancer in routine clinical practice. All patients with early-stage breast cancer (ESBC) treated by chemotherapy at Institut Curie, Hôpital René Huguenin, in 2014 were retrospectively included. The incidence and management of FN were reported. Risk factors associated with FN were studied by robust-error-variance Poisson regression. A total of 524 patients received either neoadjuvant (N = 130) or adjuvant chemotherapy (N = 394). Most patients (80%) were treated with a combination of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC100; 3cycles) followed by docetaxel 100mg/m2 (D; 3cycles). The overall incidence of FN was 17%. Eighteen percent of patients received primary prophylaxis (PP) for FN with G-CSF, using pegfilgrastim in 64% of cases and 74% of patients over the age of 70 received PP. Less than 5% of patients who received PP experienced FN. Recurrent FN after secondary prophylaxis was observed in 9% of patients. Forty-seven percent of cases of FN occurred after the first cycle and 30% occurred after the fourth cycle, corresponding to D ± trastuzumab (T). The FEC100 regimen was associated with a relative risk of FN of 1.98 (p = 0.09). Autoimmune (AI) and inflammatory diseases were associated with a higher risk of FN (RR 3.08; p < 0.01). No significant difference in the incidence of FN was observed between adjuvant and neoadjuvant chemotherapy. FN was managed on an outpatient basis in 72% of cases. Outpatients with FN were mainly treated by a combination of amoxicillin-clavulanic acid and ciprofloxacin. Dose reduction or chemotherapy regimen modification were necessary in 25% of patients after FN. No toxic death was reported. The incidence of FN induced by adjuvant/neoadjuvant chemotherapy in ESBC is higher in routine clinical practice than in clinical trials. AI or inflammatory diseases were significant independent risk factors for FN. Primary prophylaxis in patients at risk (elderly, comorbid patients), especially treated with the FEC regimen, is the keystone of management of this adverse effect. Prevention and management of FN to ensure the patient's safety and quality of life are a major issue for both medical oncologists and supportive care physicians.

Real-World Impact of a Decision Support Tool on Colony-Stimulating Factor Use and Chemotherapy-Induced Febrile Neutropenia Among Patients With Breast Cancer.

Background: White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. Methods: A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. Results: The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, -5.4%; 95% CI, -6.0% to -4.7%; P=.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, -0.20 to 0.30; P=.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. Conclusions: CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.

Risk stratification for febrile neutropenia in patients with testicular germ cell tumors.

The aim of this study was to detect risk factors for febrile neutropenia (FN) in patients with testicular germ cell tumors (TGCT). In this retrospective cohort study at the Medical University of Graz, we included 413 consecutive TGCT patients who received adjuvant or curative treatment with cisplatin‐based chemotherapy. FN occurred in 70 (16.9%) of 413 patients. In univariable logistic regression, higher age (odds ratio (OR) per 5 years = 1.17, 95% CI: 1.02–1.35, P = 0.022), reduced performance status (PS) (OR = 2.73, 1.47–5.06, P = 0.001), seminomatous histology (OR = 2.19, 1.26–3.78, P = 0.005), poor IGCCCG risk class (OR = 4.20, 1.71–10.33, P = 0.002), and prior radiotherapy (pRTX) (OR = 8.98, 2.09–38.61, P = 0.003) were associated with a higher risk of FN. In multivariable analysis adjusting for age and risk classification, only poor PS (OR = 2.06, 1.05–4.03, P = 0.035), seminomatous histology (OR = 2.08, 1.01–4.26, P = 0.047), and pRTX (OR = 7.31, 1.61–33.17, P = 0.010) prevailed. In the subgroup of seminoma patients (n = 104), only pRTX predicted for FN risk (OR = 5.60, 1.24–25.34, P = 0.025). Five of eight seminoma patients with pRTX developed FN (63%), as compared to 22 FN cases (23%) in the 96 seminoma patients without pRTX (P = 0.027). The eight seminoma patients who received pRTX had significantly lower pre‐chemo white blood counts (4.7 vs. 6.5 G/L), neutrophil counts (3.2 vs. 4.3 G/L), and platelet counts (185 vs. 272 G/L) than patients without pRTX (all P < 0.0001). TGCT patients with a reduced performance status or who had been previously treated with radiotherapy have an increased risk for neutropenic fever during chemotherapy.

Moxifloxacin versus levofloxacin for antibacterial prophylaxis in acute leukemia patients.

The primary endpoint of this study was to determine the incidence of febrile neutropenia among patients receiving either moxifloxacin or levofloxacin for antibacterial prophylaxis. Secondary endpoints were number of documented infections and in-hospital mortality in patients who develop febrile neutropenia. A single-center retrospective cohort analysis at a large tertiary care academic medical center was conducted. This study included adult acute leukemia patients (age ≥18 years old) who received inpatient antibacterial prophylaxis (moxifloxacin or levofloxacin) from 1 July 2012 to 1 October 2014. Patients were excluded from the study if they were treated with antimicrobial therapy in the preceding five days or admitted to the hospital with neutropenic fever. Fisher's exact test was used for categorical data and Mann-Whitney test for continuous data. Logistic regression analysis was used to determine risk factors for febrile neutropenia. Eighty-five patients were included in the final analysis with 40 patients who received moxifloxacin and 45 patients who received levofloxacin. Baseline characteristics were similar between the two groups. Twenty-two patients experienced febrile neutropenia requiring intravenous antibiotics in the moxifloxacin group and 30 patients in the levofloxacin group (P = 0.190). Age and duration of neutropenia appeared to predict for febrile neutropenia; however, after multivariate analysis, longer duration of neutropenia was shown to be the best predictor for febrile neutropenia with an odds ratio of 4.69 (95% CI, 1.697-12.968). Both groups had similar rates of documented infections and in-hospital morality. Moxifloxacin and levofloxacin showed similar rates of febrile neutropenia when used for neutropenic antibacterial prophylaxis in acute leukemia patients.

74P - Febrile neutropenia and primary prophylactics in docetaxel plus cyclophosphamide chemotherapy for breast cancer: A Japanese institution experience

Background: Incidence of febrile neutropenia (FN) caused by docetaxel/cyclophosphamide (TC) therapy varies widely from country to country (5% at US Oncology research trial and 68.8% at Japanese trial), and the high hematotoxicity observed in Japanese patients may reduce relative dose intensity (RDI). Methods: Between April 2009 and June 2017, 205 patients with breast cancer received TC therapy (75/600 mg/m2, every 3 weeks, 4 cycles). We investigated the incidence of FN and RDI of TC therapy and the factors related to FN and low RDI. Results: The median patient age was 53 years. Fifty-five patients received primary prophylactics (20 granulocyte-colony stimulating factor (G-CSF) and 35 antibiotics). Excluding 9 patients with allergic reaction, FN occurred in 68 patients (34.7%). Among patients with primary prophylactic G-CSF, only one developed FN, whereas FN occurred in all the 11 patients with prophylactic antibiotics. Hospitalization was required in 6.3% of patients. In multivariate analysis, the independent risk factors of FN were older age (≥60 years, p = 0.017) and without primary prophylactic G-CSF (p = 0.011). The median RDIs of docetaxel and cyclophosphamide were 96.7% and 99.7%, respectively. Low RDI (<85%) was related to older age (p < 0.001), but not to primary prophylactics (G-CSF p = 0.247 and antibiotics p = 0.862).Table: 74PPredictors of FN incidenceFactorsUnivariate analysisMultivariate analysisOdds ratio (95% CI)POdds ratio (95% CI)PAge ≥60y5.16 (2.32-11.50)<0.0012.19 (1.15-4.17)0.017Hepatic dysfunction1.85 (0.40-8.62)0.4402.39 (0.56-10.10)0.237Renal dysfunction0.28 (0.06-1.38)0.1200.82 (0.29-2.30)0.708Prophylactic G-CSF0.39 (0.08-1.92)0.2500.07 (0.01-0.54)0.011Prophylactic antibiotics1.08 (0.43-2.72)0.8600.59 (0.26-1.34)0.206 Open table in a new tab Conclusions: Even though the FN incidence of TC therapy was over 20%, low hospitalization rate and high RDI were achieved in Japanese patients. Primary prophylactic G-CSF was useful to reduce FN of TC therapy for breast cancer, especially in older patients. Legal entity responsible for the study: Hiroshima University Funding: None Disclosure: All authors have declared no conflicts of interest.

760P - Risk factors for febrile neutropenia (FN) in unresectable/recurrent pancreatic cancer(PC) patients(pts) receiving FOLFIRINOX (FFX) from JASPAC06 study

760P - Risk factors for febrile neutropenia (FN) in unresectable/recurrent pancreatic cancer(PC) patients(pts) receiving FOLFIRINOX (FFX) from JASPAC06 study

Efficacy and safety of biosimilar filgrastim in primary and secondary prevention of febrile neutropenia.

Neutropenia and febrile neutropenia (FN) are among the most common side effects/complications of chemotherapy. The aim of the present study was to evaluate the practice of the use of biosimilar filgrastim in the primary and secondary prevention of FN, and assess its efficacy and safety. A multi-center, non-interventional epidemiological study of 170 cancer patients aged 23-82 years was conducted. Data were collected via a questionnaire completed based on medical documentation and patient examination over five chemotherapy visits. The risk of FN related to the chemotherapy protocol used was in the range of 10-20% in >50% of the patients (53.5%) and a majority (74.7%) had additional FN risk factors. 60% of the patients received filgrastim as primary prevention of FN, and 40% received it as secondary prevention. In 40.6% of cases, six cycles of chemotherapy were used. More than 90% of patients continued chemotherapy according to the initial recommended dose. In majority of patients, no FN was observed following the final cycle of chemotherapy. Median neutrophil count at visit 1 was 2.2×103/µl and did not fall below that level. Majority of patients (>70%) performed self-injections of filgrastim, and 86.3% of patients were continuing therapy with this drug at the last visit. No treatment-related side effects were recorded. The use of biosimilar filgrastim in the primary and secondary prevention of FN allows to maintain initial chemotherapy dosage. Furthermore, the use of biosimilar filgrastim is safe and tolerable, and has a high acceptance by patients.

Incidence and risk factors of febrile neutropenia in patients with non-Hodgkin B-cell lymphoma receiving R-CHOP in a single center in Japan

PurposeThe incidence of and risk factors for febrile neutropenia (FN) in Japanese non-Hodgkin B-cell lymphoma (B-NHL) patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and predonisolone (R-CHOP) chemotherapy are unknown. We conducted this study to address this issue.MethodsIn this single-center, retrospective, observational study, 466 patients with B-NHL who completed an R-CHOP regimen within a 7-year period and who planned to undergo at least three cycles of this regimen were analyzed. The following FN-related factors were assessed: fever, infection, disease state, neutrophil count, and prophylactic interventions such as use of antibiotics and/or granulocyte colony-stimulating factor (G-CSF). We simulated the FN incidence and 95% confidence interval (CI) of patients without prophylaxis with G-CSF (cycle 1) using bootstrap sampling.ResultsThe incidence of FN was 9.1% (42 of 462) in cycle 1 and 12.3% (57 of 462 patients) throughout all cycles, with 73.7% (42/57) developing FN during cycle 1. Risk factors for FN among patients with B-NHL treated with R-CHOP were albumin <35 g/L (p = 0.0047), relative dose intensity <85% (p = 0.0007), and lack of prophylaxis with G-CSF (p = 0.0006) in cycle 1. In the simulation analysis, the estimated FN incidence in cycle 1 was 16.2% (95% CI [10.9–22.2]).ConclusionsAt 9.1% in cycle 1 and 12.3% throughout all cycles, the incidence of FN was lower than previously reported, possibly reflecting the appropriate use of G-CSF in this clinical setting. For patients with risk factors, the prophylaxis with G-CSF may decrease the occurrence of FN.

Safety and efficacy of same-day administration of pegfilgrastim in patients (pts) receiving chemotherapy for gastrointestinal (GI) malignancies.

10112 Background: Pegfilgrastim is typically administered 24 hours after chemotherapy per package insert; however some pts are unable or unwilling to return for this additional visit due to work or transportation especially with regimens consisting of infusional 5-FU. Same-day dosing eliminates need for this additional visit. Results from prior studies in other tumor types are inconclusive as few support same-day dosing whereas others show inferiority. Purpose of our study was to determine safety and efficacy of administering pegfilgrastim on same day as chemotherapy in pts with GI malignancies. Methods: A single-institution retrospective review was conducted of pts with GI malignancies who received chemotherapy and same-day pegfilgrastim (6 mg) within 1 hour of completion of chemotherapy from Jan 2014 through Jan 2017. Decision to administer pegfilgrastim was based on NCCN or ASCO recommendations. As per institutional guidelines, pts were counseled on risks of same-day pegfilgrastim prior to its administration. Data was collected on demographics, clinic notes and complete blood counts. Analyses included neutropenia, febrile neutropenia, hospitalization, use of antibiotics or bone pain. Results: A total of 536 chemotherapy cycles in 69 pts were analyzed. Median age was 60 years (range 32-87) with 46% of pts ≥ 65. Pts had an average of 4 risk factors for febrile neutropenia: advanced disease, gender, age &gt; 65 and chemotherapy regimen. Most common malignancy was colon (48%), pancreas (17%) and gastric (17%). Most commonly used regimens included mFOLFOX6 (42%), FOLFIRINOX (23%) and FOLFIRI (12%). Median absolute neutrophil count nadir for all cycles was 4538/uL (range: 1160-25168). Grade 1 and 2 neutropenia developed in 6 of 536 (1%) cycles. Bone pain reported in 3 pts (4%). There were no episodes of grade 3 or 4 neutropenia or febrile neutropenia. None had dose reductions, chemotherapy delays, hospitalizations, or antibiotic use due to neutropenia. Conclusions: We believe our study is the first in GI malignancies to report that same-day pegfilgrastim administration may be as effective and safe as next-day administration, benefiting pts and might reduce costs.

ZOHé: A Prospective Study of the Use of Biosimilar Filgrastim Zarzio in Clinical Practice in Patients Treated With Chemotherapy for Lymphoid Malignancies.

The ZOHé study was a prospective, observational, multicenter study in France to assess use of biosimilar filgrastim Zarzio in routine clinical practice in patients undergoing neutropenia-inducing chemotherapy. Patients≥ 18 years undergoing chemotherapy for a malignant disease and with a first prescription for Zarzio were enrolled in 2 cohorts: solid tumor (1174 patients) or hematological malignancy (633 patients); the latter is reported here. Analyses primarily described the prescription and use of Zarzio in current practice, and included identification of factors linked to prescription for primary prophylaxis, comparison of use in relation to European Organisation for the Research and Treatment of Cancer (EORTC) guidelines, and estimation of chemotherapy dose intensity maintenance in patients given Zarzio. Use of Zarzio in clinical practice was relatively standardized and followed label indication in 96.7% of the analysis population (633 patients). Most patients had≥ 2 EORTC patient-related risk factors for febrile neutropenia (FN). Chemotherapy dose intensity was maintained in 85.2% of evaluable patients and 89.6% of patients with non-Hodgkin lymphoma receiving R-CHOP (rituximab-cyclophosphamide/doxorubicin/vincristine/prednisone). The safety profile of Zarzio was confirmed. In routine clinical practice in France, Zarzio is mostly used as primary prophylaxis for chemotherapy-induced neutropenia in patients with hematological malignancies. Patient-related risk factors appear to have more weight in clinicians' decisions to give Zarzio than the FN risk category of the chemotherapy regimen alone in real-world practice.

The incidence and risk factors of febrile neutropenia in chemotherapy-naïve lung cancer patients receiving etoposide plus platinum.

This study was to determine the incidence and risk factors of febrile neutropenia in chemotherapy-naïve Japanese patients treated systemically with etoposide plus platinum for lung cancer. The study was a retrospective analysis of 244 patients who were monitored for febrile neutropenia through multiple cycles of the combination of etoposide with platinum, and the associations between incidence of febrile neutropenia and patient characteristics were evaluated. Eighty-eight patients were treated with etoposide plus cisplatin and 156 were treated with etoposide plus carboplatin. Of the 244 patients treated, 198 (81.1%) completed 4 cycles for chemotherapy. Febrile neutropenia was observed in 48 of 244 patients (19.7%), including 18 of 88 (20.5%) patients who received etoposide plus cisplatin and 30 of 156 (19.2%) patients who received etoposide plus carboplatin. Grade 3 or 4 of neutropenia was experienced by a total of 208 patients (85.2%); 79 of 88 (89.8%) receiving etoposide plus cisplatin and 129 of 156 (82.7%) receiving etoposide plus carboplatin. Male gender and previous radiotherapy were identified by multivariate analysis as independent risk factors for febrile neutropenia. These results contrast with findings in Western patients and suggest that ethnic differences exist in the incidence of febrile neutropenia in patients receiving etoposide plus platinum chemotherapy. In addition, our results suggest that primary prophylaxis with granulocyte colony-stimulating factor should be considered for patients with these risk factors for febrile neutropenia prior to treatment with etoposide plus platinum.

Reducing overuse of colony-stimulating factors without compromising patient safety: Evidence from a decision-support enabled utilization management in patients with lung cancer receiving chemotherapy.

52 Background: Recent studies suggest significant overuse of colony-stimulating factors (CSFs) for the primary prevention of febrile neutropenia (FN) in patients with cancer receiving chemotherapy. Overtreatment with CSF increases costs without evidence of clinical benefit. We examined the impact of a decision-support tool to promote risk-appropriate CSF use in lung cancer. Methods: A retrospective cohort study design was used to analyze commercial claims data on lung cancer patients. The decision-support tool was implemented at participating oncology practices in staggered phases across 14 U.S states (from July 1, 2014 - November 1, 2014). Study population included adults with lung cancer who initiated chemotherapy from July 1, 2014 through March 30, 2015. Patients were assigned to case and control cohorts according to whether or not they resided in service areas where the tool had been implemented. Patients were followed up to 6 months after initiating chemotherapy in the pre- and post-implementation periods. The primary outcomes: CSF use and FN incidence rates were compared using difference-in-differences (DID) models; adjusting for baseline FN risk factors with generalized estimating equations. Results: The final study population included 3,470 patients (case: 1,857 and control: 1,613; overall mean age (SD), years: 65 (10)). There were no meaningful differences in FN risk factors at baseline between the cohorts. In adjusted results, CSF use decreased from 48.4% to 35.6% in the case compared to a change from 43.2% to 44.4% in control cohort (DID: -8.7% (95% CI: -14.65% to -2.67%), p - &lt; 0.001) in the pre- and post-implementation periods. The rates of FN were consistent for both cohorts in each time period, with no statistical difference in trend for the case (2.8% to 4.3%) as compared with the control (3.1% to 5.1%) cohort (DID: -0.2% (95% CI: -0.63% to -0.33%), p – 0.953). Conclusions: These findings demonstrate the potential for decision-support tools to improve evidence-based guideline adherence and promote risk-appropriate CSF use in patients with lung cancer without adversely impacting patient safety.

Reducing Overuse of Colony-Stimulating Factors in Patients With Lung Cancer Receiving Chemotherapy: Evidence From a Decision Support-Enabled Program.

Colony-stimulating factors (CSFs) are frequently overused for the primary prevention of febrile neutropenia (FN) in patients receiving chemotherapy. A retrospective cohort study design was used to analyze commercial claims data in adults with lung cancer initiated on chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented at oncology practices in phases across 14 US states. Patients were assigned to intervention and nonintervention states according to whether they resided in service areas where the tool had been implemented. Patients were followed up to 6 months after initiating chemotherapy. Difference in pre- and postimplementation CSF use and FN incidence rates were compared with the use of difference-in-differences (DID) models that were adjusted for baseline FN risk factors. The study population of 3,467 patients (intervention states: pre, 707; post, 1,150; nonintervention states: pre, 636; post, 974) showed no significant differences in FN risk factors at baseline. In adjusted results before and after implementation, CSF use decreased from 48.4% to 35.6% in the intervention states versus 43.2% to 44.4% in the nonintervention states (DID, -8.7%; 95% CI, -14.65% to -2.67%; P ≤ .001). The rates of FN were consistent for both groups in both periods, with no statistical difference in trend for the intervention (2.8% to 4.3%) versus the nonintervention (3.1% to 5.1%) states (DID, -0.13; 95% CI, -0.35 to 0.10; P = .927). These findings demonstrate that a decision support-enabled utilization management tool can improve risk-appropriate, guideline-adherent CSF use in patients with lung cancer.

Abstract P5-08-06: Impact of a decision-support tool on the utilization of colony-stimulating factors and incidence of febrile neutropenia among patients with breast cancer

Abstract Background: Following the 2012 American Society of Clinical Oncology's Choosing Wisely campaign recommendation against the routine use of colony-stimulating factors (CSFs) for the primary prevention of febrile neutropenia (FN) in patients with ≤ 20% risk, an evidence-based clinical decision-support tool (CSF decision tool) was implemented to promote risk-appropriate CSF use in breast cancer patients receiving chemotherapy by a national payer in the United States (US). We hypothesized that there should be no change in pre- and post-implementation FN rates if the CSF decision tool had promoted appropriate FN risk stratification among breast cancer patients. Methods: A retrospective observational cohort study design was used to analyze data from a national payer administrative claims database of nearly 40 million lives geographically spread across the US. The CSF decision tool was first implemented in 2014, with a staggered implementation across states (July 1, 2014 - November 1, 2014). Study subjects were female patients, aged ≥ 18 years, who initiated chemotherapy for breast cancer in the time periods before or after the implementation of the decision tool (July 1, 2014 through March 30, 2015). Patients were assigned to case (defined as patients in the states where the CSF decision tool had been implemented) or control (defined as patients in states where the CSF decision tool had yet to be implemented) cohort. Patients in each cohort were followed up to 6 months after the first chemotherapy dose in the pre- and post-implementation periods. The outcomes were changes in the incidence of FN and CSF use rates, respectively. Rates of FN and CSF use were compared between the cohorts using difference-in-differences models; generalized estimating equations were used to adjust for differences in baseline risk factors including age, history of neutropenia or infections. Results: The final study population comprised 7,224 patients: 4,001 and 3,223 in the case and control cohorts, respectively. There was a higher proportion of patients who were 65 years or older in the case cohort compared to the control (22% vs 18%, p: &amp;lt;0.001). Otherwise, the cohorts were comparable in FN risk factors at baseline in pre- and post-implementation periods. In adjusted regression results, pre- and post-implementation FN rates were not significantly different for both case (5.38% to 5.65%) and control (5.07% to 5.13%) cohorts, [p=0.778]. Use of CSF in the pre- and post-implementation periods decreased from 75% to 69% in the case cohort compared with a reduction from 72% to 71% in the control cohort: an absolute difference of 5.4% decrease in CSF use associated with the implementation of the decision support tool [p= 0.006]. Conclusion: Despite a modest reduction in CSF use, we found no evidence of an increase in FN rates after the implementation of the CSF decision tool. Given the lack of impact of the Choosing Wisely campaign on inappropriate CSF use; our findings suggest that beyond the educational efforts and media campaigns, a greater reduction in unnecessary CSF use can be achieved through the use of clinical decision algorithms to reduce practice variation and improve adherence to national guideline recommendations. Citation Format: Adeboyeje G, Agiro A, Goodwin A, DeVries A, Malin J. Impact of a decision-support tool on the utilization of colony-stimulating factors and incidence of febrile neutropenia among patients with breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-06.

Value of Incorporating Newly Identified Risk Factors into Risk Prediction for Chemotherapy-Induced Febrile Neutropenia (FN)

Introduction: Chemotherapy-induced FN is a clinically important adverse event that frequently requires hospitalization and can negatively impact treatment outcomes. Clinical guidelines recommend G-CSF primary prophylaxis when a patient’s overall FN risk is >20%, so assessing individual FN risk is an essential step. Many newly discovered FN risk factors have been reported recently (eg, comorbidities such as diabetes, congestive heart failure,recent dermatologic conditions,and chronic obstructive pulmonary disease and procedures for cancer treatment). We sought to evaluate the added predictive value of these new risk factors beyond established FN risk factors.Methods: This study included patients diagnosed with lung, gastric, ovarian, colorectal, or female breast cancer or non-Hodgkin’s lymphoma (NHL) at Kaiser Permanente Southern California (KPSC) between 2000 and 2009 and treated with chemotherapy. Patients who received prophylactic G-CSF or prophylactic antibiotics were excluded. Data were collected from KPSC’s electronic medical records. The primary endpoint was FN in the first chemotherapy cycle. First, a reference model was developed based on a modified version of the FN prediction model published by Lyman et al (Cancer 2011;117:1917-27). Then a new prediction model based on the reference model plus additional newly identified FN risk factors was developed (predictors used in both models are shown in Table 1). Performance of the two models was evaluated by comparing their discriminative ability and calibration of predicted risk among the current study population. Discriminative ability was evaluated by examining the area under the receiver operator curve (AUC). Calibration of predicted risk was evaluated by comparing model-predicted risk to observed risk in the following FN risk ranges: 0-5%, 5-10%, 10-15%, and >15%. These ranges were chosen as approximately half of FN events occur in the first cycle; therefore, these ranges for FN risk in the first cycle are likely equivalent to 0-10%, 10-20%, 20-30%, and >30% risk over the chemotherapy course. Change in risk prediction at the individual patient level was also evaluated. For patients who developed FN, individual risk prediction was considered improved if the individual predicted risk drew closer to 100%; for patients who did not develop FN, individual predicted risk improved if it drew closer to 0%.Results: A total of 16,411 patients were included in the analysis (36% breast, 23% lung, 20% colorectal, 3% gastric, 6% ovarian cancer, and 12% NHL). Mean age at diagnosis was 60.5 years. Most patients were Caucasian. FN incidence in the first chemotherapy cycle was 4.0%. The odds ratios for the predictors in both models are shown in Table 1. Comparison ofFN risk predicted by both models and observed FN risk are shown in Table 2. Addingnew risk factors did not result in significant improvement in discriminative ability: AUC changed from 0.72 to 0.73. However, adding new risk factors led to a more accurate risk classification for 12% of patients (n = 1946 [425 + 569 + 282 + 64 + 382 + 132 + 92]) while it led to a less accurate risk classification for only 0.01% of patients (n = 2, Table 2). Ofthe 701patients who developed FN in the first chemotherapy cycle, adding the new risk factors increased the predicted risk for 16% ofpatients (n = 115), but decreased the predicted risk for 10% ofpatients (n = 70). Of the 15,710patients who did not develop FN, adding the new risk factors decreased the predicted risk for 5.7% ofpatients (n =973) but increased the predicted risk for 5.2% of patients (n = 811).Conclusions: Addition of the newly identified FN risk factors to the reference prediction model improved risk classification for FN in the first chemotherapy cycle. Since information on the new risk factors (including comorbidities such asdiabetes, congestive heart failure, chronic obstructive pulmonary disease, rheumatoid disease, osteoarthritis, other autoimmune diseases, peptic ulcer disease, thyroid disorder, liver disease, HIV,recent dermatologic conditions, and recent surgery)is readily available to clinicians, these factors could be incorporated into estimations of FN risk. Further refinement of the FN risk prediction model is warranted. [Display omitted] [Display omitted] DisclosuresLi:Amgen: Employment, Equity Ownership. Family:Amgen: Research Funding. Chen:Amgen: Research Funding. Page:Amgen: Employment, Equity Ownership. Klippel:Amgen: Employment, Equity Ownership. Xu:Amgen: Research Funding. Chao:Amgen Inc.: Research Funding.

Incidence and Predictors of Febrile Neutropenia among Early-Stage Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy in Korea

Objective: This retrospective study was undertaken to assess the incidence of and risk factors for febrile neutropenia (FN) during adjuvant chemotherapy for early-stage breast cancer (ESBC). Methods: A multicenter survey of three tertiary hospitals was conducted, with data extracted from the records of ESBC patients treated with adjuvant chemotherapy containing AC (doxorubicin, 60 mg/m² and cyclophosphamide, 600 mg/m² every 21 days). Assessments included clinical characteristics, chemotherapy dose modifications, and incidence of FN. Results: A total of 610 patients were included for analysis. The incidence of grade 4 neutropenia and FN was 44.6 and 8.5%, respectively. Reduced relative dose intensity (RDI) less than 85% occurred in 11.0% of patients, and there were treatment delays in 12.6% of patients. Multivariate analysis identified several independent predictors for FN, including the presence of grade 4 neutropenia and pretreatment calculated estimated glomerular filtration rate less than 60 ml/min. Conclusion: Patients with ESBC are at substantial risk for FN and reduced RDI when treated with adjuvant AC chemotherapy. Predictive models based on risk factors identified in this study should enable the selective application of supportive measures in an effort to deliver the full dose of chemotherapy.

Rates of major complications during neoadjuvant and adjuvant chemotherapy for early breast cancer: An off study population

ObjectivesTo determine the incidence and risk factors for thromboembolic events (TE) and febrile neutropenia (FN) in patients receiving systemic chemotherapy for early breast cancer (EBC). Methods325 patients received FEC75, FEC100-T or ECaP for EBC in 2013. ResultsTE occurred in 7.4% and FN in 19.1% of patients. Risk factors for TE were: central venous catheter (p = 0.011). Risk factors for FN were: FEC100-T treatment versus FEC75 and ECaP (p ≤ 0.001); lower pre-treatment neutrophil count (p = 0.009) and poorer performance status (p = 0.012). Two patients died from treatment-related toxicities. ConclusionIn real-world experience, the majority of patients completed adequate treatment, despite significant complications.

Risk factors for febrile neutropenia in cancer patients treated with chemotherapy.

6559Background: Several risk factors for febrile neutropenia (FN) have been identified in previous studies (eg, chemotherapy [chemo] dose intensity, advanced age, and comorbidities). The possible b...