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To develop a claims-based algorithm identifying systemic lupus erythematosus (SLE) flares using a linked claims-electronic medical record (EMR) dataset. This study was a retrospective analysis of linked administrative claims and EMR data spanning 1 January 2003 to 31 March 2019. Included were adult SLE patients with at least 12 months of continuous enrollment in claims data, 12 months of clinical activity in EMR, and an absence of malignancies excluding basal and squamous cell carcinoma. Patient follow-up was divided into 30-day windows, and a proxy SLEDAI-2K score based on the EMR data was calculated for each 30-day period. A flare was defined as an increase of at least 4 from the baseline score. A series of potential flare predictor variables identified in claims were based on a combination of established variables from a previous algorithm, with the addition of other SLE-related indicators based on clinical input. Logistic regression models were built to predict monthly SLE flares. Inclusion criteria identified 2427 patients. Results from a logistic model with forward selection capping the number of variables at 10 performed well with a c-statistic of 0.76 and a Brier score of 0.07. The top five predictors were any inpatient admission (OR = 4.76), outpatient office visit (OR = 3.04), MRI (OR = 2.26), ER visit (OR = 2.25), and number of rheumatology visits (OR = 1.75); p < .01 for all. The final algorithm shows promise in providing an alternative and more streamlined way for identifying likely flares in administrative claims data that will advance the study of SLE within the context of flares.

Background Objectives: Pancreatic cancer (PC) is a costly disease with a limited life-expectancy as it generally presents as an advanced, metastatic disease. Though current literature suggests cost varies by first line treatment, there is limited real-world knowledge about the economic burden of pancreatic cancer. This study describes the economic burden of pancreatic cancer patients overall and by observed first line treatments. Methods The IBM MarketScan databases were used to identify adult metastatic PC patients from January 1, 2010 through 3/31/2017. Those without other primary cancers, pregnancy, or prior PC treatment, and with 6 months of continuous enrollment prior to PC were included. Treatment patterns and healthcare utilization and expenditures were measured during the variable-length follow-up period. Continuous measures were presented as per patient per month (PPPM). Results A total of 6,360 patients met all inclusion criteria. Almost half (46.8%) of patients were untreated. Gemcitabine alone (15.6%) and FOLFIRINOX (11.4%) were the most commonly observed first line regimens. Treated patients incurred $17,513 PPPM (Gemcitabine alone) to $27,889 PPPM (FOLFIRINOX) during follow-up. Untreated patients incurred the highest unadjusted ($30,777 PPPM) and adjusted ($20,392 PPPM) cost. Conclusions Metastatic PC patients incur a high economic burden driven by high utilization of healthcare resources, which varies by first line treatment. Also, the high proportion of untreated patients is alarming as these patients may be the most expensive of all patients. There is an unmet need in these patients for effective treatments that also reduce their economic burden.

Objective Disease-modifying therapies (DMTs) can reduce multiple sclerosis (MS) relapse rates; however, effectiveness of treatments may vary. It is important to understand real-world treatment patterns in the context of MS relapses. We describe MS relapses related to treatment patterns among patients who switch treatment after their first DMT. Methods IBM MarketScan research databases were used to identify adult patients with MS who switched DMTs (index-first switch) after being newly treated with a DMT from January 2009 through March 2017, with 12 months of continuous enrollment pre- and post-index. Non-persistence was defined as discontinuing (at least 60 days without DMT) or switching DMTs. MS relapses were defined using a validated claims-based algorithm. Multivariable analysis was used to examine odds of 12-month persistence, odds of post-index relapse, and number of relapses. Results In total, 4121 patients with MS met all inclusion criteria (mean age 46.4 years; female 76.2%). Overall, 49.6% switched to an oral DMT, 36.5% to an injectable DMT, and 13.9% to an infusion DMT. Switching DMTs resulted in a 32.4% reduction in relapses between pre- and post-index. Only 54.6% of patients were persistent throughout the first year. Patients who switched to oral DMTs had 95% higher adjusted odds of persistence and 18% lower adjusted odds of a post-index period relapse than patients who switched to injectable DMTs. The number of baseline relapses was not associated with persistence but with 68% higher odds of a post-index relapse, with each additional baseline relapse associated with a 44% increase in number of post-index relapses. Conclusions Among patients with MS who switched DMTs, persistence was consistently low regardless of treatment. Although persistence with oral DMTs was slightly higher than with injectable DMTs, overall results indicate poor persistence to second-line therapy and highlight the need to improve long-term persistence with DMTs. Electronic supplementary material The online version of this article (10.1007/s12325-020-01367-1) contains supplementary material, which is available to authorized users.

This study assessed the real-world United States (US) treatment patterns and the associated economic burden in patients diagnosed with advanced hepatocellular carcinoma (HCC). The MarketScan database was used to identify patients newly diagnosed with HCC who received systemic therapy between 2011 and 2018 and continuously enrolled for ≥6 months (baseline period) prior and ≥1 month following HCC diagnosis. Treatment patterns (systemic and locoregional therapy), healthcare resource utilization, and costs were reported during follow-up. The final sample included 1580 patients (median age, 61; 78% male; median follow up, 8.7 months). The most common first line of therapy (LOT) was sorafenib (78%). The median time from HCC diagnosis to start of sorafenib was 43 days, and the median duration of sorafenib therapy was 60 days. Only 17% of patients received second LOT, and non-sorafenib treatment use increased to 66% (mostly chemotherapy combination). Transarterial chemoembolization was the most commonly observed locoregional therapy prior to the first LOT. The multivariable-adjusted average all-cause total cost among sorafenib treated patients was $17,642 (95% CI: $16,711–$18,558) per-patient per-month), of which $11,393 were HCC-specific. In patients who received first-line therapy for HCC, the duration of therapy was short (potentially due to progression or tolerability). Most patients did not continue to second-line therapy. Despite the short duration of therapy, HCC patients still incur a high economic burden, and there is a need for more effective and tolerable treatments.

49 Background: mCRPC is an incurable disease with poor prognosis. Though multiple treatments such as novel hormonal therapies (NHT: abiraterone [abi], enzalutamide [enza], docetaxel [doce], cabazitaxel [caba], sipuleucel-T [Sip-T] etc.) are approved, real-world data regarding treatment sequencing are lacking. This study assesses the real-world treatment patterns within the context of FDA-approved life-prolonging treatments for mCRPC. Methods: The IBM MarketScan database was used to identify newly diagnosed (incident) mCRPC patients from 1/1/2014-5/31/2020. Adult males were required to have a diagnosis of PC, and subsequently evidence of metastasis and castration (medical or surgical). Incident mCRPC status (index) was determined 3 ways: 1) treatment with an NHT within 3 months after castration and an FDA-approved mCRPC treatment ≥3 months after NHT; 2) first FDA-approved treatment ≥6 months after castration; 3) first FDA-approved treatment 3-6 months after castration and a second FDA-approved treatment ≥3 months after treatment. Lines of therapy (LOT) were measured in the variable-length follow-up of ≥1 month and consisted of all drugs observed within 28 days of first observed treatment. Duration of therapy was measured as start of line to start of next line or end of enrollment. Results: A total of 2,912 mCRPC patients met all study criteria and received ≥1 LOT. Among those, 48.7% had ≥2 LOT, and 21.8% had ≥3 LOT. Patients were an average age of 71 years at index and used leuprolide (87%), abi (10%), doce (9%) and enza (8%) prior to index. In mCRPC the most common observed first line (1L) monotherapy regimens were abi (35%), enza (34%), and doce (14%). The most common observed second-line (2L) treatments were enza (36%), abi (27%), and doce (14%). Mean duration of 1L was 292 days compared to 245 days in 2L. The most frequently observed treatment sequences (1L to 2L) are reported in the table. Opioids (62%) and denosumab (47%) use was common in mCRPC patients. Conclusions: Among mCRPC patients, NHTs were the most common 1st and 2nd LOTs and alternate NHT after a first NHT was the most common sequence. With rapidly evolving treatment options in metastatic prostate cancer, these data can help guide estimation of eligible patients for different clinical trials. Further studies are needed to understand the high attrition from 1L to subsequent lines of therapy, the reasons for treatment preference and impact on clinical outcomes with different treatment sequencings.[Table: see text]

Introduction: The impact of cancer care and management beyond treatment is significantly high for cancer patients. Due to the complexities of cancer treatment, patients are heavily reliant upon ancillary support often rendered by friends and family. One significant yet unquantifiable impact of cancer on society is productivity loss of both patients and their caregivers. Non-Hodgkin lymphoma is considered largely incurable with a protracted clinical course punctuated with multiple remission and relapses, warranting repeated treatment and intensive clinical testing, which necessitates significant engagement of patients and caregivers. Many patients are members of the workforce at the age of diagnosis. Both working patients and caregivers need time for medical care, which translates to indirect economic impact due to lost productivity. The objectives of this analysis were to evaluate the productivity loss and indirect costs in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or Waldenström macroglobulinemia (WM) and their caregivers. Methods: The MarketScan Commercial and Health and Productivity Management databases were used to identify patients with CLL, MCL, MZL, and WM (using ICD-9/ICD-10 codes) who were continuously enrolled for ≥6 months pre- and ≥1 month post-diagnosis (index date) from 1/1/2010 to 12/31/2019. The final study cohort included patients aged 18-64 who were full-time workers with eligibility of absentee, or short-/long-term disability on index date and for ≥1 month in follow-up. Those who were pregnant during the study period were excluded. Adult, full-time employed caregivers, defined as family members covered under the same health plan as the patient, and continuously enrolled ≥6 months pre- and ≥1 month post-index, were also identified. Among those with eligibility, the percentage with a claim of absentee, short- or long-term disability (patients only), and associated productivity time loss and indirect costs during follow-up were examined. Lost wages were calculated using the US Bureau of Labor Statistics 2019 report. For short- or long-term disabilities, mean daily wages were reduced to 70% of typical wages. Productivity time loss and costs were reported per-patient-per-month (PPPM) for each lymphoma. Results: The final patient cohort included 3,450 CLL, 448 MCL, 1,052 MZL and 394 WM patients; the caregiver cohort included 1,435 CLL, 171 MCL, 437 MZL and 190 WM caregivers. Among eligible patients, there were higher proportions of patients that had absentee claims (CLL, 76%; MCL, 72%; MZL, 72%; WM, 82%), followed by short-term disability (CLL, 16%; MCL, 36%; MZL, 18%; WM, 17%) and long-term disability (CLL, 3%; MCL, 10%; MZL, 3%; WM, 3%) (Figure 1A). The proportions of caregivers with absentee claims (CLL, 78%; MCL, 90%; MZL, 69%; WM, 75%) were also higher than those with short-term disability (CLL, 7%; MCL, 10%; MZL, 4%; WM, 8%) (Figure 1B). For all 4 lymphoma types, average illness-related absentee hours were higher in patients than caregivers (CLL, 9.5 vs 6.9; MCL, 44.5 vs 3.6; MZL, 17.0 vs 5.0; WM, 18.2 vs 8.1). A similar pattern was observed for short-term disability days (CLL, 6.9 vs 4.2; MCL, 10.8 vs 3.4; MZL, 7.0 vs 2.2; WM, 6.7 vs 4.8). Average PPPM indirect costs were higher for patients with long-term disability (CLL, $1,433; MCL, $1,233; MZL, $1,302; WM, $2,056) than with short-term disability (CLL, $1,203; MCL, $1,950; MZL, $1,145; WM. $1,177) or absentee claims (CLL, $365; MCL, $1,606; MZL, $612; WM, $662), except for patients with MCL (Figure 2A). Similar trends were observed among caregivers, though the indirect costs due to absenteeism and short-term disability were higher in patients than caregivers (Figure 2B). Conclusions: This real-world evidence study uncovered patients with CLL, MCL, MZL and WM and their caregivers incur substantial disease burden as shown by their productivity loss and indirect costs. Effective treatments that can offer a cure or better remission rates and shorter duration with less toxicity may not only enhance the patients and caregivers' quality of life but also reduce work loss. The availability of oral, targeted therapies has resulted in higher remission rates, durable responses, manageable toxicities and improved quality of life in trials. Future studies are needed to understand the impact of these oral, targeted therapies on patients' and caregivers' productivity. Figure 1 Figure 1. Disclosures Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Irwin: IBM Watson Health: Current Employment; BeiGene, Ltd.: Consultancy. Packnett: IBM Watson Health: Current Employment; BeiGene, Ltd.: Consultancy. Lew: BeiGene, Ltd.: Consultancy; IBM Watson Health: Current Employment. Noxon: BeiGene, Ltd.: Consultancy; IBM Watson Health: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Chanan-Khan: BieGene, Jansen, Ascentage: Consultancy; BeiGene, Jansen, Ascentage: Honoraria; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Cellectar: Current equity holder in publicly-traded company; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; Ascentage: Research Funding.

A 43‐year‐old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk‐exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab‐associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) (2004–2014), a FDA Advisory Committee Meeting Report, and peer‐reviewed publications. In the United States, the manufacturer maintains an FDA‐mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab‐treated patients. We statistically compared reporting completeness for natalizumab‐associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab‐associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21–74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab‐treated MS patients who developed biopsy‐confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38–48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1–77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8‐possible items, P

Purpose: The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advisory Committees warned of risks associated with erythropoiesis-stimulating agents. During this period, lawsuits alleging illegal darbepoetin marketing practices have concluded, resulting in $1.1 billion in fines and settlements and one criminal conviction. No prior study, to our knowledge, has reported on the use of darbepoetin versus epoetin for CIA. Methods: We evaluated the dosing, utilization, and costs of erythropoiesis-stimulating agents among 3,761 South Carolina Medicaid patients with CIA. Results: Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10% and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per-administration epoetin and darbepoetin doses were 40,983 IU and 191 µg, respectively, in 2003 and 47,753 IU and 369 µg, respectively, in 2010. Mean monthly patient costs for epoetin and darbepoetin were $1,030 and $981, respectively, in 2003 and $932 and $1,352, respectively, in 2010. Epoetin use decreased steadily between 2002 and 2010; darbepoetin use increased steadily between 2003 and 2007 and then decreased steadily thereafter. Per-patient dosing of darbepoetin, but not epoetin, increased steadily between 2003 and 2010, and monthly per-patient epoetin costs decreased 3% while the per-patients costs of darbepoetin increased 30% between 2003 and 2010. Conclusion: To our knowledge, our findings are the first data reporting on epoetin versus darbepoetin use for CIA and support recently concluded lawsuits involving allegations of illegal marketing practices of the manufacturer of darbepoetin.

Introduction Migraine management is characterized by the poor use of preventive therapy and the overuse of acute medications. An analysis of current treatment patterns in migraineurs is needed to improve care in this patient population. The aim of this study was to describe treatment patterns and healthcare utilization of newly diagnosed migraine patients. Methods This was a retrospective observation study of newly diagnosed migraine patients (no indication of migraine in the past year) identified in the IBM MarketScan Commercial Claims and Encounters database from 1 January 2010 to 30 June 2014. The final study population comprised persons aged 18–64 years at index (new diagnosis of migraine) with 12 months of continuous enrollment in an insurance plan with medical and pharmacy benefits pre-index and post-index. Treatment patterns and healthcare resource utilization were assessed during the post-index period (at least 12-months). Results Of the 1,588,666 migraine patients identified in the database as potentially eligible to participate in the study, 284,719 (17.9%) met the final inclusion criteria. Patients generally used acute and preventive therapies to manage migraine attacks, with most patients using preventive therapy (59.1%). However, 67.9% of those using preventive therapy discontinued the current therapy, with a median time to discontinuation of 5 months. Most of the patients who discontinued preventative therapy also used an acute treatment to manage migraine attacks after discontinuation (77.6%), generally in the year following discontinuation (68.4%). Patients on acute therapies were found to use triptans excessively (1.6%) and other non-migraine-specific acute medications for treatment (7.1%). Acute patients were also at risk of opioid dependence (12.0%) and commonly received opioids or barbiturates as first-line therapy (34.1%). Conclusion Newly diagnosed migraine patients are not being properly treated, as indicated by their excessive use of acute therapies and short time on preventive treatment before discontinuation of that treatment. Further study of the reasons why patients discontinue preventive therapy (adverse events, no response, etc.) and continue to excessively use acute treatments once their treatment regimen has been established is needed.

Aim: ECOG Performance status (PS) is a major prognostic factor in patients with metastatic pancreatic cancer (mPAC) and is one of key factors to consider in treatment selection. However, there is limited ability to determine PS through administrative claims. We aimed to establish PS based on first-line (1L) treatment to describe characteristics of mPaC patients in a claims database. Methods: The IBM MarketScan database was used to identify adult, treated mPaC patients from 2014-2018. Those with other primary cancers or pregnant during the study, chemotherapy in the 6 month pre-diagnosis (baseline) period prior to first mPaC diagnosis or those without continuous enrollment in this time were excluded. PS was assumed by NCCN guideline-recommended first-line treatment for PS. Those with first-line FOLFIRINOX or gemcitabine + nab-paclitaxel were good performers. Those with first-line gemcitabine monotherapy or gemcitabine + (capecitabine or erlotinib) were poor performers. Patients with any other first-line treatment were ungrouped. Patient characteristics were measured in the 6-month baseline period or at mPaC diagnosis. Treatment patterns were measured during the variable length follow-up which ended due to disenrollment or end of study (12/31/2018). Results: A total of 1,737 mPaC patients met all inclusion criteria, of which 59.6% were categorized as good performers and 11.6% as poor performers. Poor PS was mainly identified by gemcitabine monotherapy (99.5%) while good PS was split between gemcitabine+nab-paclitaxel (54.9%) and FOLFIRINOX (45.1%). Patients were mostly male (56.0%) with a median follow-up of 202 days and no difference by PS. Poor performers (vs. good) were significantly older (mean age 67.5 vs 61.1 years, p Citation Format: Suvina Amin, Elisabetta Malangone-Monaco, Virginia Noxon, Seongiung Joo, Michael J. Pishvaian. Using treatment to determine ECOG performance status in metastatic pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-029.

Although all disease-modifying therapies (DMTs) reduce risk of relapse in multiple sclerosis (MS), many factors, including route of administration, influence selection of first-line DMT. Knowledge of real-world treatment patterns and effectiveness in reducing relapses across DMTs is important to understanding factors influencing this choice. This study sought to describe treatment patterns and relapses among newly treated adults with MS and by DMT route of administration (oral, injectable, and infusion).IBM MarketScan research databases were used to identify MS adults newly initiating DMTs (index event) from January 1, 2011-April 1, 2016, who had 12 months of continuous preindex and postindex medical and pharmacy benefits. Newly treated patients were those with ≥2 nondiagnostic claims with an International Classification of Diseases, Ninth Revision, Clinical Modification (340) or Tenth Revision, Clinical Modification (G35) code and no DMT prescription claims in the 12 months' preindex. Persistence and adherence were measured from index until the earliest of ≥60 days without DMT, switching DMTs, or end of follow-up. Relapses were defined using a validated claims-based algorithm and measured in the 12-month preindex and postindex periods. Regression analysis adjusting for patient characteristics and prior relapses was used to determine the association between DMT route of administration and odds of 12-month persistence, odds of postindex relapse, and number of postindex relapses.Of 9378 newly treated MS patients meeting inclusion criteria; average age was 46.7 years, and 73.3% were female. Most patients initiated an injectable (65.5%) or oral (26.1%) DMT. Relapses decreased markedly from preindex to postindex (32.9%-24.0%), which was highest among oral users (35.8%-21.6%). Patients with no (vs ≥3) relapses preindex were more likely to be relapse free postindex (81.6% vs 31.4%). Nonpersistence (39.1% overall) was lowest among oral users (33.4%) and higher among those with versus without a postindex relapse (50.6% vs 35.5%). Patients initiating oral versus injectable agents were more likely to be persistent at 12 months (odds ratio [OR], 1.45; p 0.0001) and less likely to relapse (OR, 0.75; p 0.0001) postindex. Switches were uncommon (~10%) across cohorts. Preindex relapses were associated with increased odds of postindex relapses (OR, 1.73; p 0.0001) but not with odds of persistence at 12 months.The 12-month nonpersistence rate was high among all MS patients but lower among oral users. Oral users were also less likely to relapse postindex. Despite the effectiveness of DMTs in reducing relapses, the low persistence, lack of switching to a new DMT, and continued relapses highlight an unmet need in the MS treatment landscape.

ObjectiveTo examine the effects of belimumab initiation on healthcare resource utilisation (HCRU) and costs in SLE.MethodsThis retrospective observational cohort study used healthcare administrative claims data from the IBM MarketScan Commercial Claims and Encounters Database to identify patients with SLE billing codes who received ≥1 intravenous belimumab infusion between March 2011 and December 2015. The first belimumab administration was the ‘index date’. During the 6-month postindex period, nine belimumab infusions were recommended: three during the initiation period and six during the maintenance period. HCRU and cost data for inpatient admissions, emergency department visits, physician office visits, hospital-based outpatient visits, laboratory services, other outpatient services and outpatient pharmacy prescriptions were compared in the 6-month pre/postindex periods.ResultsOf the 1879 patients with SLE included, 43% received ≥3 intravenous initiation administrations. An average of 5.3 (SD: 2.4) of the nine recommended belimumab administrations were received within 6 months. In the 6-month preindex versus postindex periods, significant reductions were noted for inpatient hospitalisations (18% vs 9%, pConclusionsIn this study of real-world intravenous belimumab for SLE, adherence to recommended infusion schedules was low. Outpatient healthcare and associated costs were higher in the 6 months after belimumab was initiated, although inpatient costs were lower. Reasons for non-adherence with belimumab and implications should be investigated.

487 Background: Hepatocellular carcinoma (HCC) is often diagnosed in advanced stages. While sorafenib has been the standard of care for advanced HCC, treatment guidelines are not clearly defined. We studied real world systemic lines of therapy (LOT) and economic burden in HCC patients. Methods: The MarketScan database was used to identify patients newly diagnosed with HCC (ICD-9 155.0, ICD-10 C22.0, C22.8) from 2011-2018 and continuously enrolled for ≥6 months prior and ≥1 month post HCC diagnosis. Patients with prior liver transplantation or metastasis, or other primary cancers, pregnancy, or clinical trial participation at any time were excluded. Systemic LOT were identified and ended due to discontinuation, switch, or end of follow up. Transarterial procedures (chemoembolization [TACE], radioembolization [TARE]) were also reported. Results: A total of 1,558 patients (mean age, 62; 78% male; median follow up, 8.8 months) were studied. The first LOT was mostly sorafenib (78%). The median time from HCC diagnosis to start of sorafenib was 43 days. The median duration of therapy on sorafenib was 60 days, with patients ending sorafenib use due to discontinuation (40%) or switching (6%). Only 16% of patients received second LOT, of which 10% were PD-1 inhibitors. Use of TACE and TARE over the follow up period was 15% and 12%, respectively. TACE was more prevalent prior to first LOT (11%) compared to during first LOT (4%) and between first and second LOT (6%). This trend was also observed for TARE (7%, 3%, and 4%, respectively). Patients incurred a mean all-cause total cost of $181,036 and $17,235 per-patient per-month (PPPM), of which $9494 were HCC-specific (Table). Conclusions: Most patients received sorafenib as first line in advanced HCC, but only for 2 months. Only 16% of patients receive second line therapy. HCC patients have a high economic burden and there is a need for more effective and safe treatments. [Table: see text]

Machaon Bonafede,1 Joseph Feliciano,2 Qian Cai,1 Virginia Noxon,1 Nicole Princic,1 Akshara Richhariya,2 David J Straus3,4 1IBM Watson Health, Cambridge, MA, USA; 2Seattle Genetics, Inc., Bothell, WA, USA; 3Memorial Sloan Kettering Cancer Center, New York, NY, USA; 4John P Leonard Department of Medicine, Weill Cornell Medicine, New York, NY, USA Purpose: The purpose of this study was to evaluate the economic burden of frontline failure (FLF) among classical Hodgkin lymphoma (HL) patients during and after treatment.Patients and methods: The population consisted of adult HL patients identified from January 2010 through September 2015 without any other primary cancer prior to HL diagnosis, who also had a frontline (FL) regimen indicative of curative intent. Patients were characterized as FLF (those who restart, switch to any chemotherapy; had a hematopoietic stem cell transplant; or newly initiated radiation therapy [RT] after discontinuing FL) or non-FLF (those not considered as FLF). Direct health care utilization and expenditures were measured over both fixed and variable length follow-up periods and during FL therapy.Results: There were 77 FLF and 602 non-FLF patients who met the final inclusion criteria. FLF and non-FLF patients were demographically similar with mean age 38.5 years and 47.5% females. Average per patient per month (PPPM) costs were significantly higher for FLF patients during all follow-up (US$20,266 vs US$7,772, P

OBJECTIVES To determine patterns of use, socioeconomic factors, and the impact on total health expenses associated with triptan therapy among patients with migraines. MATERIALS AND METHODS Patients with migraines were identified from the Medical Expenditure Panel Survey household component files (2006 to 2011) and were restricted to those who were 18 years or older and had a migraine diagnosis. The major outcome measures were triptan use during the 2-year period and annualized average total and migraine-related health care expenses and medical utilization. Socioeconomic factors associated with triptan use were analyzed by using logistic regression. The impact of triptan use on total and migraine-related health expenses was assessed by linear regression models with log transformations. RESULTS Among 1961 patients with a migraine diagnosis (representing 45.6 million individuals in the United States for years 2006 to 2011), 501 received triptans to treat acute migraines (representing 13.1 million individuals in the United States, 28.6%). Patients who were females and had higher income and education levels were more likely to receive triptans to treat migraines. Triptan expense accounted for 49.6% of total migraine-related expenses and 21.9% of total all-cause prescription drug expenses respectively. Compared with nontriptan users, the annualized total health expenses increased by 19.7% in triptan users after adjusting for demographic and health-related variables. DISCUSSION The study suggested that socioeconomic factors were associated with triptan use in migraineurs. Higher total and migraine-related health expenses were observed in triptan users.

Summary Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents—molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs—provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.

To determine predictors associated with the diabetes self-management education and training (DSME) venue and its impact on oral antidiabetic (OAD) medication adherence.The Medical Expenditure Panel Survey household component (MEPS-HC) data (2010-2012) identified adults with diabetes prescribed OAD medication(s) who completed a supplemental Diabetes Care Survey (DCS). Based on the DCS responses to questions about the number and type of DSME venue(s), two groups were created: (1) multiple venues (a physician or health professional plus internet and/or group classes) vs (2) single venue (physician or health professional only). The medication possession ratio (MPR) measured medication adherence, with 0.80 the cut-point defining adherent. Logistic regression examined factors associated with the DSME venue and its effect on OAD medication adherence.Of the 2119 respondents, 41.6% received DSME from multiple venues. Age (65years), education-level (college or higher), high-income, and diet modification were significantly more likely associated with receiving DSME from multiple venues. In single vs multiple venues, medication adherence was suboptimal (mean MPR 0.66 vs 0.64, p=0.245), and venue showed no influence on adherence (OR: 0.92, 95% CI, 0.73-1.16).Sociodemographic characteristics influence where adults with diabetes receive DSME. Adding different DSME venues may not address suboptimal OAD medication adherence.

e12576 Background: Triple-negative breast cancer (TNBC) accounts for 10–20% of all breast cancers and about 4% are metastatic (mTNBC) at diagnosis. This research aims to describe treatment patterns and associated adverse events (AEs) among mTNBC patients. Methods: MarketScan Commercial Claims and Encounters and Medicare Supplemental Database, linked to an oncology EMR database, was used to identify patients with mTNBC. Demographic factors, clinical characteristics, mTNBC treatment patterns (treatment type and initial regimen), and the incidence of associated AEs (rates per 100 person-years) were tabulated. Patients seen in oncology practices between January 1, 2011 and June 30, 2015 were included in the study and were required to have continuous enrollment overlap in the administrative claims data for 6 months before the first diagnosis and throughout the variable-length follow-up period. Follow-up ended due to death, end of continuous enrollment, or end of study (whichever occurred earlier). Results: The study identified 163 mTNBC patients with a mean age of 55 years. The average length of follow-up was 569 days and 34% died during the study period. Diabetes mellitus (22%) and anemia (16%) were the most common comorbid conditions at baseline. During the follow-up period, the majority of mTNBC patients received treatment (76%); the most common first-line treatments included cyclophosphamide (60%), paclitaxel (56%), doxorubicin (52%), carboplatin (25%), and docetaxel (23%), averaging 96 days in duration. In 47% of patients, treatment ended due to a switch. Over 96% of the patients experienced at least one AE during treatment, the most common being hematological (neutropenia, leukopenia, and anemia), gastrointestinal (nausea and vomiting), and other (pyrexia, fatigue, and dyspnea) [see table]. Conclusions: Several different chemotherapy agents were used to treat mTNBC. Adverse events were common among mTNBC patients initially treated with chemotherapy; the highest incident AEs were hematological. [Table: see text]

Objectives To identify socioeconomic factors associated with mail-service pharmacy use and compare the differences in disease-specific prescription medication and medical utilization expenses in a nationally representative sample of adults with diabetes. Design A retrospective, longitudinal, cross-sectional study. Setting United States in 2006–11. Participants Medical Expenditure Panel Survey household component (MEPS-HC) participants aged 18 years or older diagnosed with diabetes and prescribed antidiabetic medications. Main outcome measures Likelihood of mail-service pharmacy use, diabetes-related medical utilization, and medication expenses. Results Among 4,430 eligible participants identified in the 2006–11 surveys, representing more than 83 million U.S. individuals, nearly 13% of the participants obtained two-thirds or more of their antidiabetic medications via mail service predominantly. Mail-service pharmacy users were older, had high school or college degrees, had higher incomes, and were more likely to be covered by private insurance. There were no significant differences in diabetes-related medical utilization and drug expenses between the two groups. Conclusion Besides pharmacy benefit design, sociodemographic and economic factors influenced drug dispensing channel use (mail service versus community pharmacy). No significant differences in diabetes-related drug and medical expenses between mail-service and community pharmacy users were observed.

Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L) or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L). This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility.

As of 2013, the Southern Network on Adverse Reactions (SONAR) team described 50 significant adverse drug reactions (sADRs) associated with FDA approved drugs. The team also investigates policy issues surrounding pharmacovigilance. Herein we describe the systematic approach to pharmacovigilance taken by the Southern Network on Adverse Reactions and discuss major findings from the group. By 2015, the team hopes to have identified 20 additional sADRs focusing on biologics, biosimilars, and biobetters. The ultimate goal of SONAR is to decrease the timescale between ADR detection and the dissemination of information regarding the sADR

e18237Background: Natalizumab is an effective therapy for multiple sclerosis. Its most notable toxicity is PML. The FDA mandated registry, TOUCH, focuses on PML cases. We identified an unusual case...

Background: Darbepoetin and epoetin are erythropoiesis stimulating agents (ESAs) that have been used to treat chemotherapy related anemia in cancer patients since 2002 and 1993. ESAs reduce rates of blood transfusions in both CKD and cancer patients. In the cancer setting, toxicities for ESAs include venous thromboembolism (VTE), tumor progression, and death. In March 2007, these toxicities were described by FDA in a revised "black box" warning. The warning advised clinicians to use the lowest dose possible of ESAs among persons with chemotherapy associated anemia and to administer ESAs to cancer patients who are receiving chemotherapy for palliation versus the curative setting. While several studies report decreased ESA utilization among cancer patients with chemotherapy-induced anemia following the Black Box warning, these studies have not reported on changes in ESA use for darbepoetin versus epoetin nor have they reported on changes in VTE rates. We report on darbepoetin versus epoetin utilization trends in cancer patients with chemotherapy-associated anemia in addition to VTE and transfusion rates during the years 2002 to 2010. Methods: We merged South Carolina Medicaid data with South Carolina Cancer Registry dataset for the years 2002- 2010. Breast, non-small cell lung and colorectal patients 18 years of age and older evaluated. From the chemotherapy population in this cohort based on tumor registry data, ESA users were identified from medical and pharmacy claims. The final sample contained persons with a first ESA claim after chemotherapy administration among Medicaid persons who are not dually enrolled in Medicare and Medicaid. Results: Of 1,315 chemotherapy patients who received an ESA, 940 (71%) were darbepoetin users and 375 (29%) were epoetin users. In 2002, epoetin and darbepoetien users accounted for 37.5% and 13% of the chemotherapy population respectively. Epoetin users decreased to 13% for 2004-2006 and declined further to 3.4% by 2010. Darbepoetin administration increased to 43.5% in 2005 among cancer patients receiving chemotherapy and decreased to 7.1% among chemotherapy patients by 2010. Among chemotherapy patients who received epoetin, VTE rates were 8% in 2002 and 3% in 2010 (p Conclusion: Among cancer patients with chemotherapy-associated anemia who received ESAs between 2002 and 2010, darbepeotin users exhibited a decrease in utilization, little to no response in VTEs or transfusion risks, and marked increases in per cycle and per month dosing. In contrast, epoetin users showed decreased utilization, decreased per-cycle and per-month dosing, decreased VTE rates, and increased transfusion rates. The Black Box warning appears to have had differential effects on epoetin- versus darbepoetin-treated cancer patients with chemotherapy associated anemia. Table 1. Epoetin Darbepoetin 2002 2007 2010 2003 2007 2010 Utilization 38% 9% 3% 33% 35% 7% Transfusions 2% 6% 12% 4% 7% 6% VTEs 8% 4% 3% 6% 7% 5% Mean Total Monthly Dose 110,026 IU 95,507 IU 99,625 IU 328mcg 403mcg 452mcg Differences between epoetin and darbeoetin patients from 2002-2010 Disclosures No relevant conflicts of interest to declare.

e17623 Background: Clinical trials have identified increased risks of venous thromboembolism and mortality with ESA administration to cancer patients and increased risks of arterial thrombosis with...

Background: Erythropoietin stimulating agents (ESAs), have been readily used to treat chemotherapy related anemia in cancer patients since 2003. ESAs are a useful substitute for blood transfusions for these patients. However, there were unacknowledged toxicities for ESAs when they were first administered. In March 2007, these toxicities were acknowledged by the FDA when a black box warning was issued for ESAs in these patients. This study aims to observe ESA utilization trends along with VTEs to determine the effect of the black box warning. Methods: The 2002-2010 merged South Carolina Medicaid- Cancer Registry dataset with Medicaid claims up to 2012 was used to determine the effect of the FDA black box warning. Breast, non-small cell lung and colorectal patients were determined from the cancer registry. Of these, those who had chemotherapy were identified. ESA users were identified from medical and pharmacy claims. The final sample contained those who had their first ESA claim after chemotherapy and who were not dual enrolled in Medicare. Results: Of the 1,645 cancer patients with chemotherapy, 1,310 (80%) had at least one ESA claim. Total ESA claims by year showed a peak in 2006 at 2,243 claims followed by a decrease to 1,347 in 2007 and 714 in 2006. A month by month breakdown of ESA claims showed the peak in May 2006 at 250 and eventually decreasing to 7 in December 2012. Total VTE events for these patients showed a peak in 2007 at 811 followed by a steep decline to 351 in 2009 and 154 in 2012. Conclusion: The FDA black box warning may have been effective in reducing ESA utilization. There is also the potential delayed response to the clinical trial data for VTEs and ESA utilization. The meta-analysis in 2008 by Dr. Bennett also seems to have had an impact on reducing ESA utilization and VTE events. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Folic acid deficiency is thought to be procarcinogenic because it promotes the incorporation of genomic uracil. Base excision repair (BER) normally prevents genomic instability by removing procarcinogenic base lesions. However, BER might paradoxically contribute to folate deficient-carcinogenesis if the pathway is initiated but cannot be completed, resulting in the accumulation of BER intermediates (DNA strand breaks). DNA polymerase ≤ (POLα) performs two key steps in BER and so we utilized human metastatic breast cancer cells in which the expression of POLα has been eliminated or transgenically expressed to determine the influence of POLα on chromosomal stability. We found that folic acid deficiency induced premature chromatin condensation (PCC) and strand breaks in POLα deficient cells, demonstrating that folic acid deficiency and BER deficiency induce chromosomal instability. We also examined the expression and localization of PARP1, a key component of BER and strand break repair. PARP1 was not cleaved during folic acid deficiency, suggesting that apoptosis was not occurring under these conditions. More interestingly, PARP1 was dramatically re-localized within the nucleus in POLα deficient cells. We are currently examining the effect of PARP inhibitors and the activation of PARP under these conditions. Collectively, the data suggests that folic acid deficiency in combination with deficiency in POLα is capable of inducing gross chromosomal instability that invokes DSB repair pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2549. doi:1538-7445.AM2012-2549