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Acute myeloid leukemia (AML) prognosis is poor, with sustained remission occurring in

Background This study analyses treatment patterns, health care resource utilization (HCRU), and costs in patients with myelofibrosis (MF) and a subgroup treated with ruxolitinib (RUX). Materials and Methods Treatment patterns, all-cause and MF-related HCRU, and costs were analyzed in adults with MF with continuous enrollment in a commercial or the Medicare Advantage health plan in the pre-index period, defined as the 12 months immediately prior to the index date (date of primary or secondary MF diagnosis), and the post-index period, defined as ≥6 months following the index date. In a subgroup analysis, outcomes were analyzed in patients treated with optimal RUX (OPT RUX, ≥30 mg) and suboptimal RUX (SUB RUX, Results Of 2830 patients with an MF diagnosis, 1191 met eligibility requirements. The median age of patients was 72 years, 54% were male, and comorbidities were frequent. Sixty percent of patients received ≥1 line of therapy (LOT), of which 46% (n = 331) had ≥2 LOTs during the post-index MF period. Costs increased considerably 6-month pre-index to 6-month post-index (all-cause: cause ($24,216 to $48,966) and MF-related ($16,502 to $39,383), driven by inpatient stays and pharmacy costs. In the subgroup analysis, patients treated with RUX (n = 495) experienced significant disease burden and high costs, regardless of dose. A shorter duration of therapy and a higher rate of discontinuation were observed in patients treated with SUB RUX (n = 191) versus OPT RUX (n = 304). Conclusion These findings suggest a significant disease and economic impacts associated with MF patients that persists with RUX therapy, highlighting the need for additional therapeutic options for MF.

Background: TNBC disproportionally affects younger women and is the leading cause of cancer-related deaths in women under 40. Treatment burden likely has a greater impact in younger women given employment and/or parental status. Little is known about treatment-related healthcare utilization, costs, or absenteeism or disability in women with mTNBC. This study describes real-world treatment patterns and the economic burden of mTNBC among patients treated with a first line (1L) chemotherapy. Methods: A retrospective cohort analysis of IBM MarketScan(R) Commercial and Medicare Supplemental Claims Databases was conducted. The analysis included adult female patients diagnosed with mTNBC who initiated 1L therapy from 1/1/2011 - 9/30/2017. Patients were continuously enrolled with medical and pharmacy benefits > 6 months prior to mTNBC diagnosis date and the start of 1L chemotherapy (index date) and for 3 mos after the index date. End of 1L was defined by treatment change, discontinuation (>60-day gap), or inpatient death or hospice. Patient follow-up was from the index date to the end of continuous enrollment or the end of the study period, 12/31/2017. Baseline demographic, clinical characteristics and per patient per month (PPPM) healthcare utilization and costs were analyzed descriptively. Indirect productivity burden of mTNBC using employed patient’s absenteeism (ABS), short-term disability (STD), and long-term disability (LTD) are reported. All costs are 2017 US dollars. Results: 1,027 patients with mTNBC meeting eligibility criteria were identified. Median age was 55 years; 69.5% of women were ages 45 - 64. Mean Charlson Comorbidity Index score was 8.8. Of the 27 1L treatments observed, the 3 most common were cyclophosphamide/doxorubicin (44.7%), cyclophosphamide/docetaxel (10.1%), and paclitaxel (7.7%). Median time to treatment post diagnosis was 27 days. Observed median follow-up time was 271 days; 13.2% of patients remained on 1L chemotherapy to end of follow-up. Mean duration of 1L treatment was 86 days (SD, 67 days); 69.2% of patients had a change in 1L treatment. For all-cause healthcare utilization during 1L, 11.6% patients had an inpatient admission, 16.9% had an ED visit, and 98.0% had an outpatient visit, of which 80.7%, 52.7%, and 98.8% were breast cancer-related, respectively. Mean all-cause total healthcare costs and outpatient prescription costs were $17,727 (SD $13,701) and $10,861 (SD $10,136) PPPM, respectively. Of breast cancer-related treatments, all patients received chemotherapy, 4.9% received radiation therapy, 1.2% underwent breast cancer surgery, and 96.5% received supportive care. The mean total breast cancer-related treatment cost was $10,322 (SD $9,512) PPPM. At 6 months post-index, 56 patients (5.5%) had either ABS, STD, or LTD data eligibility. Of this subset, 4 (7.1%) patients had an ABS claim and missed an average of 245 work-hours and had a mean productivity loss of $6,472. STD and LTD claims were available for 14 (25.0%) and 4 (7.1%) patients who experienced an average of 63 and 76 work-days lost and a mean loss of $9,265 and $11,192, respectively. Conclusion: Patients with mTNBC continue to experience significant treatment burden. Moreover, though many therapies were observed, limited long term treatment options are available suggesting a need for a durable treatment options that also minimize the burden for patients. Citation Format: Ashley Tabah, Ronda Copher, David Huggar, Marc Tian, Sarah S. Mougalian. Treatment patterns and costs of metastatic triple negative breast cancer (mTNBC) in US women: A retrospective cohort study of first-line chemotherapy [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 P2-08-09.

Enasidenib was approved by the Food and Drug Administration in 2017 for the treatment of patients with relapsed or refractory (RR) acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. Given limited data in clinical practice, this study assessed real-world clinical outcomes and healthcare resource use in patients with RR AML. Physicians performed chart abstraction of patients with RR IDH2-mutated AML treated with enasidenib (between 1/2018 and 6/2019) or other first-line (1 L) RR therapy (between 1/2016 and 7/2017). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and adjusted risk of progression and death were estimated by multivariable Cox proportional hazard models. Among 124 patients treated with enasidenib and 76 patients treated with other 1 L RR therapy, overall response rate was higher among patients treated with enasidenib vs. other 1 L RR therapies (77% vs. 52%, p lt; 0.01). After a median follow-up of 9 and 6 months, median PFS was 8 months in enasidenib-treated patients and 5 months in patients receiving other 1 L RR therapy, respectively (adjusted HR=0.36, 95% CI: 0.23-0.57, p lt; 0.01). Median OS was 11 and 6 months in enasidenib-treated patients and patients receiving other 1 L RR therapy, respectively (adjusted HR=0.37, 95% CI: 0.22-0.60, p lt; 0.01). Fewer enasidenib-treated patients were hospitalized during 1 L RR therapy vs. those receiving other therapies (14% vs. 46%, p lt; 0.01). Results from this real-world study confirm the effectiveness of enasidenib among patients with IDH2-mutated RR AML and demonstrate that hospitalizations were significantly lower vs. other 1 L RR treatment in clinical practice.

Introduction Little is known about real-world use of small molecule kinase inhibitors (SMKI) for advanced thyroid cancer in the United States. This study examined prescribing patterns of SMKI agents recommended by the National Comprehensive Cancer Center (NCCN). Methods This retrospective study used a national health insurance database to identify patients diagnosed with thyroid cancer during 1/1/2006–6/30/2016 and with prescription claims for NCCN-recommended SMKI during 1/1/2010–5/31/2016 whose first claim date was the index date. Inclusion also required continuous enrollment in a health plan for 3 months pre-index (baseline) and ≥ 1 month post-index (follow-up) with no claims for SMKI during baseline. Lines of therapy (LOT) were defined by the date of SMKI claims and days of drug supply. Median time to SMKI discontinuation in each LOT was estimated by Kaplan–Meier method. Results The study included 217 patients. During follow-up (mean duration 499.0 days), 35.5% of patients (n = 77) received a second or later LOT; among patients with ≥ 12 months follow-up after first LOT (LOT1) initiation, 53.1% (n = 60) received a second or later LOT. Median treatment duration was 5.0 months for LOT1 and 5.1 months for LOT2. Over the entire follow-up period (2010–2016), sorafenib was the most common regimen in LOT1 (36.9% of patients) and LOT2 (24.7%) followed by sunitinib and levantinib (13.4% each) in LOT1 and sunitinib (19.5%) in LOT2. Starting in 2015, the year lenvatinib was approved for differentiated thyroid cancer, lenvatinib was the most common first-line regimen among patients initiating LOT1 in 2015 (43.4%) and 2016 (66.7%). Conclusion Sorafenib was the most common first-line agent during 2010–2014 but was supplanted by lenvatinib starting in 2015. Approximately 36–53% of patients received a second-line treatment. Median treatment duration results suggested potential benefit of SMKI in second-line therapy. SMKI treatment after first-line failure may be considered for appropriately selected patients. Funding Eisai, Inc. (Woodcliff Lake, NJ).

Background Eribulin mesylate is approved for the treatment of metastatic breast cancer (mBC) after two prior chemotherapy regimens including an anthracycline or a taxane in either the metastatic or adjuvant setting. Eribulin in combination with trastuzumab (E+T) has demonstrated tolerability and anti-tumor activity in phase I and II trials but is not FDA-approved for the treatment of HER2-positive mBC. Case series and retrospective research have noted the use of E+T in clinical practice. We sought to describe patient characteristics and long-term outcomes of treatment with E+T for HER2-positive mBC patients treated outside of clinical trials in the US. Methods US-based community oncologists from an open network of over 7,000 oncologists, hematologists, and urologists were invited to participate in identifying HER2-positive mBC patients treated with E+T between 01/01/11 and 12/31/13 outside of clinical trials. Data were collected from 03/18/2016 until 09/01/2016. Providers completed an electronic case report form (CRF) by abstracting data on disease characteristics, treatment patterns, disease response (per provider assessment), adverse events (Aes), and date of death. Duration of treatment and overall survival (OS) were calculated from the initiation of the E+T regimen. The target sample size was 60 patients and patients were selected according to resource available for chart data abstraction. Results Twenty-three providers submitted CRFs for 62 total patients. After data collection, 59 of 62 submitted records were validated for analysis. At mBC diagnosis, 69.4% of patients were ER/PR negative and 42.4% of patient had de novo stage IV disease. At initiation of E+T, the median age was 57 years and 81.4% were ECOG-OS 0/1. Mean length of follow-up from the initiation of any therapy was 33.6 months. Twenty-two (37.3%) patients initiated E+T as their first- or second-line of treatment; those remaining were in third-line or greater. At initiation of E+T, 72.8% of patients had prior treatment with trastuzumab in combination with chemotherapy, 25.4% had prior trastuzumab in combination with pertuzumab and chemotherapy, and 16.9% had received TDM-1. Mean duration of E+T treatment was 5.2 months (SD=2.4). A response (complete [CR] or partial [PR]) was recorded by the providers for 64.4% of patients (not independently verified). The most common Aes reported were fatigue (67.8%), weakness (50.8%), decreased appetite (28.8%), decreased hemoglobin (27.1%), peripheral neuropathy (25.4%), and neutropenia (18.6%). At the end of the study period, 34 patients (57.6%) were deceased; the median OS from the initiation of E+T was 23.9 months (95% CI: 17.8-30.4). Conclusions In a small cohort of patients treated with E+T in the community setting, the observed response rate of 64.4% (CR+PR) was comparable to that of a prior phase II trial of E+T which reported an ORR with first-line E+T of 71.2% overall, 77.4% among T-naïve and 61.9% in T-pretreated patients. Further research is warranted to examine the tolerability and efficacy of E+T for metastatic HER2-positive breast cancer patients in different treatment settings. Citation Format: Mougalian SS, Copher R, McAllister L, Radtchenko J, Wang EC, Broscious M, Yu H-T, Kish J. Outcomes of real-world use of eribulin plus trastuzumab for HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-28.

Introduction: Previously, we assessed the economic burden of newly diagnosed acute myeloid leukemia (AML) among Medicare patients and found that the economic burden of relapse is high, at approximately 1.2 and 1.6 times the monthly per-patient costs associated with early and late post-remission therapy, respectively (Tabah A, et al. Blood 2020:136(suppl 1):45). A notably high proportion of patients (55%) received ≥ 1 cycle of a hypomethylating agent (HMA). Therefore, the objective of this study was to assess the economic burden of AML among a subgroup of elderly patients who received only HMA monotherapy during induction and then achieved disease remission. Healthcare resource utilization (HCRU) and costs associated with various phases (ie, induction, post-remission therapy, and post-relapse) were assessed. Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, which comprised Medicare claims (parts A, B, and D from 2007 through 2016) and the US National Cancer Institute's SEER database (cancer diagnoses from 2007 to 2015). Included patients had an AML diagnosis in the SEER registry, were ≥ 65 years of age at the AML diagnosis date, had initiated HMA (and no other active treatment) in the outpatient (OP) setting during the first induction cycle post-AML diagnosis, and had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) diagnosis code for AML remission following the initiation of induction therapy. Patients were excluded if they had another blood malignancy (including a history of myelodysplastic syndromes), had received hematopoietic stem cell transplantation, or were enrolled in a clinical trial. The induction therapy period was defined as the first initiation of HMA post diagnosis (index date) to the end of the cycle during which a patient had a code for AML remission. The 6-month period prior to the index date was defined as the baseline period. The post-remission phase ended at the earliest of relapse or end of follow-up (ie, death, end of eligibility, or end of available data [December 31, 2016]). The post-relapse phase was from the date of first AML relapse ICD-9/10 code after remission to the end of follow-up. Patient characteristics during the baseline period were summarized descriptively. HCRU and costs (adjusted to 2019 US dollars) associated with induction and post-remission therapy were assessed during days that were part of a treatment cycle. The average per-patient monthly HCRU and costs were reported for the induction, post-remission, and post-relapse phases. Results: A total of 71 patients with newly diagnosed AML (azacitidine: n = 31; decitabine: n = 40) received HMA induction therapy and achieved remission. The median age at AML diagnosis was 78.8 years, 50.7% of patients were male, and 85.9% were White. The mean ± standard deviation (median) time from index date to the end of follow-up was 16.0 ± 12.3 (14.0) months. A total of 63.4% of patients (n = 45) received post-remission therapy. Among all patients, 43.7% relapsed and 85.9% died by the end of follow-up. OP visits were the most common type of visit across all phases with 95.6% of patients having ≥ 1 OP visit during post-remission therapy and 83.9% during the post-relapse phase. Inpatient (IP) visits were highest in the post-relapse phase with 77.4% of patients having ≥ 1 IP visit. The monthly mean per-patient healthcare costs were highest for the post-relapse phase, followed by post-remission therapy, and induction (Table). Costs associated with the OP setting were the greatest contributor to the induction costs (48.9%) while costs associated with the IP setting were the drivers of the costs in the post-remission therapy (56.2%) and post-relapse (72.8%) phases. Conclusions: The economic burden of AML treated with HMA induction therapy was highest in the post-relapse phase, at approximately 1.7 and 1.6 times the monthly per-patient costs during the induction and post-remission therapy phases, respectively. In addition, IP costs made up nearly two-thirds of total monthly per-patient costs in the post-relapse phase, up from approximately 44% and 56% of the induction and post-remission therapy phases, respectively. Treatment options that extend the post-remission phase would reduce the high economic burden associated with AML relapse. Figure 1 Figure 1. Disclosures Brunner: Celgene, Forty Seven Inc, Jazz: Other: Advisory Board; Novartis, Celgene, Takeda, AstraZeneca: Research Funding. Huggar: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Copher: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Zhou: Sanofi: Research Funding; Analysis Group: Current Employment, Other: Employee of Analysis Group which received consulting fees for this project . Zichlin: Analysis Group, Inc.: Consultancy, Current Employment; GlaxoSmithKline: Research Funding. Anderson: Analysis Group, which received consultancy fees from GSK: Consultancy, Current Employment. Downes: nalysis Group (employment), Bristol Myers Squibb (consultancy): Consultancy, Current Employment. McBride: BMS: Current Employment.

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy. In the United States (US) in 2020, the incidence of AML was 4.3/100,000, with a death rate of ~2.8 per 100,000. Following diagnosis, for patients who are fit for high-dose therapy, standard of care consists of initial intensive remission-inducing chemotherapy followed by post-remission therapy comprising consolidation chemotherapy alone, hematopoietic stem cell transplantation (HSCT) alone, or consolidation chemotherapy followed by HSCT. Despite an initial response to treatment, most patients with AML progress, and relapse is common. Relapse in AML is associated with poor prognosis, substantial healthcare resource utilization (HCRU), and a cost burden. Maintenance therapy with newer agents may delay relapse and prolong survival. Understanding HCRU and costs of newly diagnosed AML may inform clinicians, policy makers, and payers on the burden of AML and the potential clinical and economic benefits of novel therapies. This retrospective study describes HCRU and costs for patients with newly diagnosed AML receiving intensive induction chemotherapy in the US. METHODS: The Premier Healthcare Database was used to identify patients aged ≥18 years with an inpatient hospitalization or hospital-based outpatient visit (01/01/2016-03/31/2019), an AML diagnosis (ICD-10-CM diagnosis codes: C92.00, C92.40, C92.50, C92.60, C92.A0), who received CPX-351 or 7+3 treatments, and had ≤280 days from the end of first induction treatment to remission. Patients with prior AML diagnosis or those receiving other treatments were excluded. Index date was the admission date for the first hospitalization or the first hospital-based outpatient visit with an AML diagnosis. Patients were followed until death, relapse or last known follow-up, whichever was first. Unadjusted descriptive analyses were performed for patient demographics, baseline clinical characteristics, outpatient days, inpatient hospitalizations, intensive care unit (ICU) admissions, and costs. RESULTS: Overall, 642 patients who received induction chemotherapy for newly diagnosed AML were identified. Mean (median) patient age was 53.7 (56.0) years, and 53.1% of patients were male. Patients had commercial (47.2%), Medicare (26.8%), Medicaid (17.6%), or other (8.4%) insurance. Mean (SD) Charlson Comorbidity Index was 3.5 (2.2), and the most common comorbidities were diabetes (20.3%), chronic pulmonary disease (15.4%), and congestive heart failure (9.4%). Most frequent adverse events were pyrexia (47.2%), neutropenia (39.9%), sepsis (28.0%), pneumonia (24.3%), and fungal infection (17.9%). Median (interquartile range [IQR]) time from the end of first induction chemotherapy to remission was 58 (40-90) days. Median (IQR) time from remission to relapse was 274 (141-389) days. A total of 385 (60.0%) patients had outpatient service days at a Premier facility; median (IQR) number of outpatient service days per patient was 3 (1-6), outpatient hospital cost per visit was $1,083 ($481-$2,189), and total outpatient hospital cost was $2,904 ($1,054-$7,217). All patients had an inpatient hospitalization; median (IQR) number of inpatient hospitalizations per patient was 2 (2-3), length of stay (LOS) per inpatient hospitalization was 16 (13-21) days, cost per inpatient hospitalization was $34,558 ($25,419-$49,460), and total inpatient hospital cost was $83,440 ($63,067-$113,985). A total of 144 (22.4%) patients had an ICU admission; median (IQR) number of ICU admissions per patient was 1 (1-1), LOS per ICU admission was 3 (2-8) days, cost per ICU visit was $15,771 ($7,209-$27,564), and ICU cost was $16,550 ($7,368-$36,968). CONCLUSIONS: In the US, healthcare costs for patients with newly diagnosed AML who receive induction chemotherapy are considerable, primarily due to high HCRU and lengthy inpatient stays. Patient response to induction therapy and duration of remission may also contribute to HCRU and costs. More tolerable therapies that improve remission rate and duration, and/or reduce hospitalization rates, may alleviate the economic burden of AML. Disclosures Huggar: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Knoth: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Copher: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Cao: Premier, Inc.: Current Employment; BeiGene, Ltd.: Consultancy. Lipkin: Premier, Inc.: Current Employment. McBride: Bristol Myers Squibb: Current Employment. LeBlanc: Amgen: Consultancy, Other: travel; BMS/Celgene: Consultancy, Honoraria, Other: Travel fees, Research Funding, Speakers Bureau; Flatiron: Consultancy, Other: Advisory board; Astellas: Consultancy, Honoraria, Other: Advisory board; Duke University: Research Funding; American Cancer Society: Research Funding; Helsinn: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Advisory board, Research Funding; Heron: Consultancy, Honoraria, Other: advisory board; Agios: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; Pfizer: Consultancy, Other: Advisory Board; CareVive: Consultancy, Other, Research Funding; Seattle Genetics: Consultancy, Other: Advisory board, Research Funding; Jazz Pharmaceuticals: Research Funding; Otsuka: Consultancy, Honoraria, Other; Daiichi-Sankyo: Consultancy, Honoraria, Other: Advisory board; AbbVie: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; UpToDate: Patents & Royalties; NINR/NIH: Research Funding.

46 Background: Alternative payment models (APMs) aim to address the rising cost of cancer care ($173 billion in 2020) by promoting high-value care. This study explored the challenges and opportunities associated with implementation of APMs in oncology practice sites across the U.S. Methods: A novel survey was created through literature review and a focus group of content experts and researchers. This survey was distributed electronically (Qualtrics) to oncology/hematology physicians (MDs) and quality officers (QOs) at U.S academic (AC) and community (CO) cancer centers from August 2020 to November 2020. Each participant reported on their center’s experience with APMs. A descriptive analysis was conducted. Results: A total of 136 sites were contacted and 28 sites (13AC/15CO) participated (21% response rate). There were 30 (67%) sites that implemented an APM, the most common was the CMS Oncology Care Models (CMS OCM) (87%, n=26), which typically took 6 months or less for implementation (66%, n=20) and was reported to improve benchmark performance (63%, n=10). The most common reasons APMs were not implemented were administrative complexity (53%, n=8); difficulty with alignment of multiple payers to APM (47%, n=7); and need for a median of 5 full-time hires. A larger number of QOs indicated participation in CMS OCM compared to MDs [94% (n=15) vs. 76% (n=11)]. The biggest difficulty experienced by MDs was adoption of innovation at site’s financial risk (43%, n=6) compared to QOs who focused on administrative and financial burden (43%, n=7). Community cancer sites were more likely to use APMs (100%, n=23) compared to AC sites (31%, n=7). The largest difficulty experienced by CO sites was adoption of innovations at their own financial risk (26%, n=6) compared to high costs, administrative burden and lack of payer engagement (29%, n=2 each) for AC sites. The most common challenge with incentives among CO sites was concerns with risk adjustment of quality measures (57%, n=13) compared to increased complexity of incentive compensation (57%, n=4) for AC sites. CO sites indicated that quality measure performance reviews were primarily conducted by administrative staff compared to clinical leaders for AC sites. Conclusions: Administrative burden and access to appropriate patient data inhibit the impact of APMs. MDs are primarily concerned about the penalties and financial risk, whereas QOs focus on administrative complexities. For CO and AC sites, the adoption and implementation of APMs to improve cost and care delivery was not without significant challenges. This study demonstrates the multifaceted impact APMs have on care delivery.

Several organizations have developed frameworks to systematically assess the value of new drugs.To evaluate the convergent validity and interrater reliability of 4 value frameworks to understand the extent to which these tools can facilitate value-based treatment decisions in oncology.Eight panelists used the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), Institute for Clinical and Economic Review (ICER), and National Comprehensive Cancer Network (NCCN) frameworks to conduct value assessments of 15 drugs for advanced lung and breast cancers and castration-refractory prostate cancer. Panelists received instructions and published clinical data required to complete the assessments, assigning each drug a numeric or letter score. Kendall's Coefficient of Concordance for Ranks (Kendall's W) was used to measure convergent validity by cancer type among the 4 frameworks. Intraclass correlation coefficients (ICCs) were used to measure interrater reliability for each framework across cancers. Panelists were surveyed on their experiences.Kendall's W across all 4 frameworks for breast, lung, and prostate cancer drugs was 0.560 (P= 0.010), 0.562 (P = 0.010), and 0.920 (P0.001), respectively. Pairwise, Kendall's W for breast cancer drugs was highest for ESMO-ICER and ICER-NCCN (W = 0.950, P = 0.019 for both pairs) and lowest for ASCO-NCCN (W = 0.300, P = 0.748). For lung cancer drugs, W was highest pairwise for ESMO-ICER (W = 0.974, P = 0.007) and lowest for ASCO-NCCN (W = 0.218, P = 0.839); for prostate cancer drugs, pairwise W was highest for ICER-NCCN (W = 1.000, P0.001) and lowest for ESMO-ICER and ESMO-NCCN (W = 0.900, P = 0.052 for both pairs). When ranking drugs on distinct framework subdomains, Kendall's W among breast cancer drugs was highest for certainty (ICER, NCCN: W = 0.908, P = 0.046) and lowest for clinical benefit (ASCO, ESMO, NCCN: W = 0.345, P = 0.436). Among lung cancer drugs, W was highest for toxicity (ASCO, ESMO, NCCN: W = 0. 944, P0.001) and lowest for certainty (ICER, NCCN: W = 0.230, P = 0.827); and among prostate cancer drugs, it was highest for quality of life (ASCO, ESMO: W = 0.986, P = 0.003) and lowest for toxicity (ASCO, ESMO, NCCN: W = 0.200, P = 0.711). ICC (95% CI) for ASCO, ESMO, ICER, and NCCN were 0.800 (0.660-0.913), 0.818 (0.686-0.921), 0.652 (0.466-0.834), and 0.153 (0.045-0.371), respectively. When scores were rescaled to 0-100, NCCN provided the narrowest band of scores. When asked about their experiences using the ASCO, ESMO, ICER, and NCCN frameworks, panelists generally agreed that the frameworks were logically organized and reasonably easy to use, with NCCN rated somewhat easier.Convergent validity among the ASCO, ESMO, ICER, and NCCN frameworks was fair to excellent, increasing with clinical benefit subdomain concordance and simplicity of drug trial data. Interrater reliability, highest for ASCO and ESMO, improved with clarity of instructions and specificity of score definitions. Continued use, analyses, and refinements of these frameworks will bring us closer to the ultimate goal of using value-based treatment decisions to improve patient care and outcomes.This work was funded by Eisai Inc. Copher and Knoth are employees of Eisai Inc. Bentley, Lee, Zambrano, and Broder are employees of Partnership for Health Analytic Research, a health services research company paid by Eisai Inc. to conduct this research. For this study, Cohen, Huynh, and Neville report fees from Partnership for Health Analytic Research. Outside of this study, Cohen receives grants and direct consulting fees from various companies that manufacture and market pharmaceuticals. Mei reports a grant from Eisai Inc. during this study. The other authors have no disclosures to report. Study concept and design were contributed by Bentley and Broder, with assistance from Elkin and Cohen. Bentley took the lead in data collection, along with Elkin, Huynh, Mukherjea, Neville, Mei, Popescu, Lee, and Zambrano. Data interpretation was performed by Bentley and Broder, along with Elkin, Cohen, Copher, and Knoth. The manuscript was written primarily by Bentley, along with Elkin and Broder, and revised by Bentley, Broder, Elkin, Cohen, Copher, and Knoth. Select components of this work's methods were presented at ISPOR 19th Annual European Congress held in Vienna, Austria, October 29-November 2, 2016, and Society for Medical Decision Making 38th Annual North American Meeting held in Vancouver, Canada, October 23-26, 2016.

Background Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs) and a significant proportion of all BC deaths. Eribulin is approved for the treatment of metastatic BC (MBC) after treatment with two prior regimens. A pooled analysis of two phase III studies of eribulin in women with TNBC patients found a 26% reduction in the risk of death vs. controls. Treatment patterns of eribulin and clinical outcomes associated with early vs. late use among TNBC patients treated in community oncology practices have not been evaluated. Methods Physicians from the Cardinal Health Oncology Research Network completed an electronic case report form (CRF) on up to 7 TNBC patients treated with eribulin between 01/01/11 and 12/31/13. Adult female patients with pathologically confirmed metastatic disease and not participating in any interventional clinical trial were included. Providers indicated the usage of chemotherapy, either alone or in combination, by line of therapy (LOT) up to the LOT of eribulin initiation. Reported data points include: clinical parameters (eg, site of metastases, ECOG performance status, and comorbidities), treatment events (eg, LOT start/end date and rationale for discontinuation), and outcomes (eg, clinical response and date of death). Dosing, adverse events, use of supportive care medications, and hospitalization were also captured during eribulin treatment. Use of eribulin in LOT 1/LOT 2 was considered early; LOT 3+ was considered late. All comparisons are univariate. Results An interim analysis was performed on 123 TNBC patients (planned sample size of 250) collected from 26 providers. Patient mean age at eribulin treatment initiation was 55.0 years. Mean follow-up duration was 27 mo (SD = 11.9) from initiation of first line metastatic treatment until date of last visit, death, or loss to follow-up. Overall, 74.0% were deceased, 85.4% had received at least 3 LOTs in the metastatic setting, and 45.4% were stage IV at diagnosis. Most women were prescribed eribulin in a later LOT (61.8%), 3 (2.4%) patients received eribulin in LOT1 and 44 in LOT2 (36.7%). Among patients with known treatment start and end dates (87.0%), mean duration of treatment (DOT) was 6.2 mo (SD = 3.3), median 5.8 mo among early recipients and 5.5 mo (SD = 5.7), median 4.1 mo, among later recipients (p = 0.39). Early users were more likely (p = 0.05) to have a complete/partial response (71.1% vs. 47.7%) and less likely to have progressive disease (7.1% vs. 12.3%). In comparing eribulin users to all other therapies, eribulin users had a significantly longer DOT in LOT2 (5.9 vs. 4.7 mo, p = 0.01) and LOT3 (5.8 vs. 3.6 mo, p = 0.03). In LOT3, eribulin users were significantly more likely to have complete/partial response (54.2% vs. 18.8%) and less likely to have to have progressive disease (4.2% vs. 37.5%) compared to all other observed LOT3 therapies. Conclusions This interim analysis indicates longer DOT for patients treated with eribulin for TNBC in LOT2 and LOT3 and a more favorable response rate compared to all other agents used in each LOT, respectively, among patients treated in community oncology practices. Full results will be available at the conference. Citation Format: Kish JK, Mougalian SS, Copher R, McAllister L, Zhixiao W, Broscious M. Utilization and outcomes of eribulin in triple negative metastatic breast cancer: Real-world findings [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 P5-15-16.

Background Several organizations have developed frameworks to systematically assess the value of new drugs. These organizations include the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the Institute for Clinical and Economic Review (ICER), and the National Comprehensive Cancer Network (NCCN). Objectives To understand the extent to which these four tools can facilitate value-based treatment decisions in oncology. Methods In this pilot study, eight panelists conducted value assessments of five advanced lung cancer drugs using the ASCO, ESMO, and ICER frameworks. The panelists received instructions and published clinical data required to complete the assessments. Published NCCN framework scores were abstracted. The Kendall's W coefficient was used to measure convergent validity among the four frameworks. Intraclass correlation coefficients were used to measure inter-rater reliability among the ASCO, ESMO, and ICER frameworks. Sensitivity analyses were conducted. Results Drugs were ranked similarly by the four frameworks, with Kendall's W of 0.703 ( P = 0.006) across all the four frameworks. Pairwise, Kendall's W was the highest for ESMO-ICER ( W = 0.974; P = 0.007) and ASCO-NCCN ( W = 0.944; P = 0.022) and the lowest for ICER-NCCN ( W = 0.647; P = 0.315) and ESMO-NCCN ( W = 0.611; P = 0.360). Intraclass correlation coefficients (confidence interval [CI]) for the ASCO, ESMO, and ICER frameworks were 0.786 (95% CI 0.517–0.970), 0.804 (95% CI 0.545–0.973), and 0.281 (95% CI 0.055–0.799), respectively. When scores were rescaled to 0 to 100, the ICER framework provided the narrowest band of scores. Conclusions The ASCO, ESMO, ICER, and NCCN frameworks demonstrated convergent validity, despite differences in conceptual approaches used. The ASCO inter-rater reliability was high, although potentially at the cost of user burden. The ICER inter-rater reliability was poor, possibly because of its failure to distinguish differential value among the sample of drugs tested. Refinements of all frameworks should continue on the basis of further testing and stakeholder feedback.

Introduction: The Oncology Care Model (OCM) is an innovative payment model introduced by the Centers for Medicare & Medicaid Services in 2016, which aims to improve quality and reduce the cost of cancer care. Under this framework, practices are incentivized to reduce spending in chemotherapy-centered episodes. Previous studies using data from pre-OCM periods (i.e. before July 1, 2016) suggested that reducing OCM episode costs, particularly disease-specific drug costs, may adversely affect overall survival (OS) in patients with multiple myeloma (MM). Using more recent data that covers 1.5 years after OCM implementation, the current study aimed to evaluate trends in OCM-defined episode costs and OS over time. Additionally, the association between OCM-defined MM episode costs and OS in MM, as well as changes in the association between the pre- and post-OCM periods, were evaluated. Methods: Patients with newly diagnosed MM (NDMM) and ≥ 1 qualifying OCM-defined MM episode between 2012 and 2017 were selected from the 100% Medicare data. OCM episodes were defined as the 6-month period following a triggering MM treatment claim. Each episode was linked to a practice and classified based on participation in the OCM and occurrence of pre- versus post-OCM implementation. Regression models were developed, based on the OCM algorithm, to adjust for case severity mix at the practice level. The models evaluated the impact of patient and episode characteristics on total episode costs, and episode subcomponents (e.g. MM-specific drugs, other medical treatment). Based on the regression outputs, standardized costs were calculated for each practice, adjusting for differences in patient and episode characteristics. All costs were inflated to 2017 US dollars (USD). From initial MM diagnosis, mean unadjusted episode costs, mean standardized episode costs, and 1-year OS rate were described over time by the year of first episode initiation. Two Cox proportional hazards models were constructed for OS with adjustment for key patient covariates (i.e. age, gender, comorbidity index, race, number of OCM episodes, and disability entitlement). Model 1 evaluated the association between OS and standardized total episode costs and the proportion of episode costs attributed to MM-specific drugs. Model 2 evaluated the effect on OS of the interaction between the time period (i.e. pre-OCM vs post-OCM) and total standardized episode costs. The analyses were repeated for key patient subgroups stratified by comorbidity status (i.e. low Charlson Comorbidity Index [CCI] vs high CCI) and practice type (i.e. OCM vs non-OCM). Results: A total of 17,363 patients with NDMM (51.0% male) were included in the analysis. Mean age at diagnosis was 74.8 years (30.0-102.0). Patient characteristics were comparable between pre-OCM and post-OCM periods. There were a total of 41,972 OCM episodes during the mean 2.2 years (standard deviation [SD] 1.4) of follow-up. Average (SD) MM-drug costs, other medical and drug costs, and total costs per OCM episode were USD 51,482 (USD 31,752), USD 22,625 (USD 28,452), and USD 74,107 (USD 38,606), respectively. From 2012 to 2017, average total episode costs, MM-drug costs, and survival all increased (Table). Model 1 indicated that a USD 10,000 increase in standardized total costs was associated with a 27.5% lower risk of death (hazard ratio [HR] 0.725; P < 0.05) and that MM-drug costs were the primary driver for the improved OS. The hazard of death decreased by 21.3% (HR 0.787; P < 0.05) for every 10% increase in the proportion of costs attributed to MM-drug costs versus other medical costs. Model 2 showed the association was similar during pre-OCM and post-OCM periods. Consistent results were observed between subgroups of high versus low CCI and OCM versus non-OCM practices. Conclusions: The analysis identified a positive correlation between average spending within OCM-defined episodes and OS among patients with NDMM, demonstrating observable clinical value for patients. This correlation remained consistent across pre-OCM and post-OCM periods. A closer evaluation of the cost subcomponents suggested that MM-specific drug costs are a primary driver for the observed OS benefit. Patient benefit from the innovative, albeit higher cost, therapies is noteworthy given the improved survival of MM. Careful evaluation is warranted for healthcare providers when attempting to reduce spending in response to new payment models. Disclosures Niesvizky: BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Clancy:BMS: Current Employment, Current equity holder in publicly-traded company. Copher:Bristol Myers Squibb: Current Employment. Thomas:BMS: Current Employment. Qi:BMS: Other: Employee of Analysis Group Inc., which received consulting fees; Astellas Pharma, Inc.: Research Funding. Zhou:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Zichlin:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Koenigsberg:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Signorovitch:BMS: Other: Employee of Analysis Group Inc., which received consulting fees.

Introduction: The safety and efficacy of 1L dasatinib and 1L imatinib was established in the pivotal DASISION and IRIS trials; however, limited real-world evidence exists for the comparative effectiveness of these agents among US patients with CP-CML treated in routine clinical practice. As such, real-world data are needed to assess the outcomes of imatinib- and dasatinib-treated patients in a pragmatic setting. Additionally, recent data suggest that second generation tyrosine kinase inhibitors (TKIs), including dasatinib, may be beneficial in certain CP-CML populations, which may be underrepresented in clinical trials (e.g., high risk, elderly, or high body mass index [BMI]). This study examined the real-world clinical response rates and time to response associated with 1L dasatinib or 1L imatinib among patients with CP-CML, as well as in subgroups defined by Sokal risk, age, and BMI. Methods: A retrospective, observational, US multi-site cohort study was conducted among adults with newly diagnosed Philadelphia chromosome-positive CP-CML treated with 1L dasatinib or 1L imatinib between January 2014 and September 2018. Patients had at least 1 year of follow-up after 1L initiation and did not have another malignancy or treatment as part of any clinical trial for CML. Oncologists collected data from eligible patient charts, including patient characteristics, treatment details, response to dasatinib or imatinib, and survival. Response was classified as major molecular response (MMR) and deep molecular response (DMR: 4.5-log reduction in BCR-ABL1 transcript levels) by physician report. Patient characteristics and outcomes were summarized using descriptive statistics for dasatinib and imatinib; results were reported in aggregate and stratified by Sokal risk (low and intermediate/high), age (< 65 and ≥ 65 years old), and BMI (low/normal [< 25 kg/m2] and high [≥ 25 kg/m2]). Comparisons were made by chi-square or Fisher's exact test for categorical variables, t-test or Wilcoxon test for continuous variables, log-rank test for overall survival (OS), and Cox proportional hazard models using Fine and Gray's method to account for competing risks in estimating differences in time to response across groups. Results: Among the patients treated with 1L dasatinib (n = 309) and 1L imatinib (n = 304), median follow-up time was 27.4 and 28.9 months, respectively. Most patients initiated dasatinib at 100 mg (82%) or imatinib at 400 mg (95%). Dose reductions were more common among dasatinib patients vs imatinib (15% vs 7%, P < 0.01), though fewer dasatinib-treated patients discontinued for any reason (15% vs 28%, P < 0.01). Higher rates of MMR were seen in dasatinib vs imatinib patients (79% vs 65%, P < 0.01) and median time to MMR was shorter with dasatinib vs imatinib (11.9 vs 14.7 months, P < 0.01). Similarly, higher rates of DMR were seen among dasatinib vs imatinib patients (44% vs 25%, P < 0.01) along with a shorter median time to DMR with dasatinib vs imatinib (30.3 vs 66.1 months, P < 0.01). Among patients with intermediate/high Sokal risk, as well as those < 65 years old, rates of MMR and DMR were higher and achieved earlier with dasatinib vs imatinib (all P < 0.01) (Table). Low-risk patients treated with dasatinib had higher rates of DMR vs imatinib (60% vs 32%, P = 0.01). Among patients ≥ 65 years old, rates of MMR and DMR were numerically higher with dasatinib vs imatinib, though differences were not significant at α = 0.05. Across both BMI strata, rates of MMR and DMR were higher with 1L dasatinib vs 1L imatinib (all P < 0.05). In the overall population, dasatinib patients had superior OS compared to those treated with imatinib (98% vs 89%, P < 0.01). Conclusions: In real-world clinical practice, a greater proportion of patients with CP-CML treated with 1L dasatinib achieved MMR and DMR and also achieved these responses earlier vs 1L imatinib. These clinically meaningful improvements were also observed across patient subgroups stratified by Sokal risk, age, and BMI. These findings from real-world US data were consistent with DASISION, demonstrating that dasatinib yields better outcomes among patients with CP-CML, with the novel findings of improved OS and improved outcomes in certain subgroups, including a higher rate of DMR among low-risk patients. Disclosures Klink: Cardinal Health: Current Employment, Current equity holder in publicly-traded company. Keating:Bristol Myers Squibb: Current Employment. Brokars:Bristol Myers Squibb: Current Employment. Kee:Bristol Myers Squibb: Current Employment. Copher:Bristol Myers Squibb: Current Employment. Stwalley:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Feinberg:Cardinal Health: Current Employment. Jabbour:Takeda: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding.

Introduction: Acute myeloid leukemia (AML) is a malignant form of bone marrow cancer commonly diagnosed in older adults. The age-adjusted incidence of AML in the USA is 4.3 per 100,000, with a median age of 68 years at diagnosis. Once diagnosed, treatment options include intensive chemotherapy to induce remission followed by post-remission therapies, including stem cell transplantation, repeated rounds of intensive chemotherapy to achieve durable disease control, or supportive care. Prognosis following relapse is poor with a median survival of 8-10 months. While previous studies have shown that much of this time following relapse is spent in an inpatient or outpatient setting, few studies have looked at the frequency and costs of this healthcare utilization. This study examined annual healthcare resource utilization and associated costs incurred in patients diagnosed with relapsed AML. Methods: A retrospective analysis was conducted in the Premier Healthcare Database, a nationally representative, all-payer hospital administrative database containing more than 1 billion inpatient and hospital-based outpatient encounters. Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for AML in relapse, the study identified adult patients during the period from January 1, 2016 to March 31, 2019. The date of the first encounter with a relapse diagnosis served as the index date. Patients were followed from index date to inpatient death, one year post-relapse, or end of study period (September 30, 2019). Unadjusted descriptive analyses were performed to describe patient demographics, hospital characteristics, and comorbid conditions, as well as outcomes of interest, including outpatient treatment days, inpatient and intensive care unit (ICU) admissions, and associated costs. Results: A total of 2,290 patients were identified for inclusion in the study. Mean age was 61.2 years (median 65.0 years) and 46.9% were female. Healthcare coverage was Medicare (51.2%), commercial insurance (29.1%), Medicaid (13.8%), or other (5.9%). Mean Charlson Comorbidity Index was 4.02 (SD 2.66) and common comorbidities were diabetes (31.0%), congestive heart failure (19.5%), and chronic obstructive pulmonary disease (19.0%). Patients' length of follow-up varied: < 90 days (49.4%), ≥ 180 days (32.8%), and ≥ 360 days (16.8%). During the 1-year follow-up period, patients were seen in the outpatient hospital treatment setting for a median of 7.0 (IQR 2-19) days. In addition to outpatient treatment, patients incurred a total of 1,798 inpatient hospitalizations (median 2.0 per patient, IQR 1-3), with a median length of stay (LOS) of 10.0 (IQR 6-19) days. Among hospitalized patients, 554 (30.8%) included an ICU admission with a median LOS of 3.0 (IQR 1-5) days per admission. Median cost per day for outpatient treatment was $1,039 (IQR $487-2,305) and patients incurred a median cost of $6,569 (IQR $1,872-23,542) in this setting. For hospitalizations, median cost of an inpatient stay was $21,592 (IQR $9,852-45,000). Cost of an ICU admission during a hospital stay was $13,348 (IQR $6,115-28,266). Hospital treatment costs incurred by this cohort of patients in the year following relapse totaled $169 million, of which 82% ($139 million) was attributable to the inpatient setting. Conclusions: After a relapse of AML, patients are commonly admitted to the hospital, oftentimes to the ICU, and incur substantial costs associated with treatment. These results suggest that cost savings could be realized with therapies that would forestall relapse and improve survival in patients with AML. Disclosures Tabah: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Knoth:Bristol Myers Squibb: Current Employment. Huggar:FibroGen: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Karyopharm Therapeutics: Current equity holder in publicly-traded company. Copher:Bristol Myers Squibb: Current Employment. Cao:Bristol Myers Squibb: Research Funding; Precision Xtract: Current Employment. Lipkin:Premier Inc.: Current Employment; Bristol Myers Squibb: Other: Premier Inc. received funding from BMS to conduct this research. Leblanc:UpToDate: Patents & Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding.

Introduction:Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the unregulated proliferation of myeloid cells in the bone marrow and their accumulation in the blood. The approval of imatinib (IM) and second-generation TKIs have substantially improved survival for patients with CML. Despite the effectiveness of these TKIs in controlling CML, continuous therapy is necessary for most patients, and may be associated with the development of unfavorable adverse events such as hepatotoxicity. Although patients with elevated liver function tests are excluded from key clinical trials, case reports and small single-center studies have described cases of TKI-associated hepatotoxicity among patients with CML. This study sought to describe the prevalence and incidence of hepatotoxicity in patients with newly diagnosed Philadelphia chromosome-positive chronic-phase (Ph+ CP) CML treated with 1L TKIs in community oncology practices. Methods:This retrospective, observational cohort study identified adult patients newly diagnosed with Ph+ CP CML and treated with 1L dasatinib (DAS), IM, or nilotinib (NIL) within the US Oncology Network (USON) between 1 January 2008 and 30 November 2018. Patients were required to have at least one comprehensive metabolic panel (CMP) within 90 days of treatment start, and ≥ 1 CMP during follow-up. Additionally, patients had to have at least two visits within the USON, no enrollment in any clinical trial during the study period, and no documentation of other primary cancer diagnoses. Descriptive statistics were generated for baseline patient characteristics and prevalence and incidence of hepatotoxicity, and were stratified by 1L TKI treatment initiation. Grades for hepatotoxicity were derived from laboratory data using the Common Terminology Criteria for Adverse Events version 5. Results:A total of 2743 patients with CP-CML were identified. Of those, 730 (26.6%), 1455 (53.0%), and 558 (20.3%) patients were treated with 1L DAS, IM, or NIL, respectively. With the exception of age and region, patient demographic characteristics were well balanced across cohorts. However, baseline hepatic functioning differed across TKIs (Table 1). Prevalence of any-grade liver enzyme elevation was observed in almost one-third (31.9%) of patients, including 246 (33.7%) patients treated with DAS, 416 (28.6%) patients treated with IM, and 213 (38.2%) patients treated with NIL. Among all patients with normal baseline hepatic function, 48.9% developed any-grade hepatotoxicity while on 1L therapy. Across TKI cohorts, significantly more patients treated with NIL developed any-grade hepatotoxicity (70.1%) compared to patients treated with DAS (45.5%) or IM (43.5%) (P< 0.0001). Among all patients receiving 1L treatment, 1.5% to 3.8% of patients experienced grade 3-4 hepatotoxicity. Significant differences in the proportion of patients that developed grade 3-4 hepatotoxicity were observed across treatments and were most common among patients treated with NIL (Table 2). Conclusions:Findings from this analysis suggest that hepatic dysfunction may be common at baseline among patients with CP-CML treated in real-world community oncology settings. Among patients with normal baseline hepatic function, more patients treated with NIL experienced any-grade hepatotoxicity. Patients treated with NIL were also more likely to develop grade 3-4 hepatotoxicity compared to patients treated with DAS or IM. These findings may provide insight into the effects of long-term TKI treatment on hepatic functioning and help to inform treatment choices for patients. Disclosures Kolibaba: AbbVie:Research Funding;Compass Oncology:Ended employment in the past 24 months;Janssen:Research Funding;TG Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;McKesson Life Sciences:Consultancy;Sumitomo Dainippon Pharma Oncology:Consultancy, Other: travel, accommodations, expenses, ;Gilead:Research Funding;Genentech:Research Funding;Cell Therapeutics:Research Funding;Celgene:Research Funding;Acerta:Research Funding;Atara Biotech:Membership on an entity's Board of Directors or advisory committees;Verastem:Honoraria;Seattle Genetics:Research Funding;Novartis:Research Funding;Pharmacyclics:Research Funding.Zhou:McKesson Corporation:Current Employment.Keating:Bristol Myers Squibb:Current Employment.Clark:McKesson Life Sciences:Current Employment, Current equity holder in publicly-traded company.Brokars:Bristol Myers Squibb:Current Employment.Kee:Bristol Myers Squibb:Current Employment.Copher:Bristol Myers Squibb:Current Employment.Stwalley:Bristol Myers Squibb:Current Employment, Current equity holder in publicly-traded company.Jabbour:Adaptive Biotechnologies:Other: Advisory role, Research Funding;Genentech:Other: Advisory role, Research Funding;BMS:Other: Advisory role, Research Funding;Amgen:Other: Advisory role, Research Funding;Pfizer:Other: Advisory role, Research Funding;Takeda:Other: Advisory role, Research Funding;AbbVie:Other: Advisory role, Research Funding.

Introduction: For medically fit patients with AML, intensive chemotherapy (IC) is used to induce complete remission (CR). Following CR, some patients may be considered for curative-intent hematopoietic stem cell transplantation. For others, the aim of treatment is to prevent relapse, which usually occurs within 1 year from CR. Post CR, treatment may include consolidation therapy, consisting of chemotherapy given soon after CR is achieved. In addition, maintenance therapy with intravenous (IV) or subcutaneous (SC) injection of AZA has shown evidence of statistically significant improvement in unadjusted time to relapse, though not in unadjusted overall survival (OS), vs placebo (PBO) in randomized controlled trials (RCTs) (Wei. 2019). In the QUAZAR AML-001 trial, maintenance with CC-486, an oral hypomethylating agent, resulted in significant improvements in unadjusted time to relapse and OS vs PBO (Wei et al. 2019). No head-to-head trials have compared CC-486 with AZA. Objective: To assess the relative efficacy of CC-486 compared with AZA. Methods: A systematic literature review was conducted to identify RCTs assessing AML maintenance therapy with AZA, for comparison with CC-486. Bayesian network meta-analysis (NMA) compared endpoints of CC-486 and AZA. Hazard ratios (HR), 95% credible intervals (CrI), and surface under the cumulative ranking curve (SUCRA) values were calculated. The impact of differences in potential treatment-effect-modifying characteristics between populations in the NMA was explored using anchored matching-adjusted indirect comparison (MAIC). The NMA was repeated using CC-486 vs PBO efficacy from the MAIC, to satisfy the assumption of clinical similarity necessary in NMA (Hoaglin et al. 2011). Results: Four RCTs evaluating OS outcomes that could be compared were identified: QUAZAR AML-001 (CC-486) (Wei et al. 2019), HOVON 97 AML (SC AZA) (Huls et al. 2019), UK NCRI AML16 (SC AZA) (Burnett et al. 2015), and QoLESS-AZA-MLE (SC and IV AZA, included in sensitivity analysis) (Oliva et al. 2019). Other efficacy and safety endpoints were not analyzed owing to lack of comparable data among the 4 identified RCTs. Results of the NMA indicated CC-486 was associated with statistically significant improvement in OS vs SC AZA (HR 0.744; CrI 0.557, 0.998); SC AZA was not statistically different from PBO (HR 0.926; CrI 0.771, 1.120). SUCRA values associated CC-486 with the best OS (98.8%). In a sensitivity analysis, CC-486 was associated with statistically significant improvement in OS vs SC or IV AZA (HR 0.741; CrI 0.556, 0.992). In the MAIC, a structured process was used to evaluate the need for adjustment due to differences in trial populations in the NMA. Populations for each trial were compared (Table). Per methodological guidance (Phillippo et al. 2016), the MAIC sought to adjust characteristics with evidence of (a) treatment-effect-modifying status on the scale of parameters entering the NMA and (b) substantial imbalance across populations. Using the QUAZAR individual patient data, univariate analyses were conducted to determine prognostic and effect-modifying status of variables (Table). For each SC AZA trial, a multivariate Cox model was estimated, including all significant prognostic variables reported, and effect modifiers that remained significant when controlling for prognostic variables and improved model fit. Among variables reported for UK NCRI, no effect modifiers enhanced the multivariate model; for HOVON, treatment interactions with age > 81 years (the oldest age in HOVON) and absolute neutrophil count (ANC) did. MAIC was therefore conducted by re-weighting QUAZAR patients to match means/shares of the HOVON patients, adjusting for mean age, % aged > 81 years, % poor cytogenetic risk, and mean ANC. Effective sample size was 411 (−13% vs N = 472 in QUAZAR). Frequency-weighted, unadjusted (including only a treatment covariate) Cox regression was conducted. After adjusting for effect-modifying differences, the OS improvement of CC-486 vs PBO observed in QUAZAR was maintained in the HOVON population. Incorporating the adjusted HR from the MAIC in the NMA, CC-486 continued to be associated with statistically significant improvement in OS vs SC AZA (HR 0.753; CrI 0.563, 0.998). Conclusion: Maintenance CC-486 appears to significantly improve OS compared with SC AZA for patients with AML who have achieved CR after IC, based on a systematic analysis of RCT outcomes. Disclosures Tabah: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Huggar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Karyopharm Therapeutics: Current equity holder in publicly-traded company; FibroGen: Current equity holder in publicly-traded company. Wang:Medicus Economics: Current Employment; Bristol Myers Squibb: Research Funding. Johnson:Medicus Economics: Current Employment; BMS: Research Funding. Copher:Bristol Myers Squibb: Current Employment. O'Connell:Bristol-Myers Squibb: Consultancy; Other biopharmaceutical manufacturers: Consultancy; Medicus Economics, LLC: Current Employment. Leblanc:AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; UpToDate: Patents & Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; AstraZeneca: Research Funding.

Introduction: Acute myeloid leukemia (AML) poses significant economic burden on the healthcare system, particularly during induction therapy and at disease relapse. The burden associated with ongoing post-remission therapy is less clear. In patients diagnosed with AML enrolled in Medicare who received an induction therapy and achieved disease remission, we assessed the healthcare resource utilization (HCRU) and costs associated with each disease period (induction, early/late post-remission, and post-relapse). Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, comprising Medicare claims (parts A, B, and D from 2007 to 2016) and the US National Cancer Institute's SEER database (cancer diagnoses from 2007 to 2015). Identified patients had a diagnosis of AML in the SEER registry, were ≥ 65 years at the AML diagnosis date, initiated chemotherapy post-AML diagnosis (i.e. induction), and had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) diagnosis code for AML remission following the start of therapy. Patients were excluded if they had another blood malignancy, had received a prior hematopoietic stem cell transplant, or were enrolled in a clinical trial. Induction was defined as any therapy received from the date of first post-diagnosis chemotherapy initiation (index date) to the end of the cycle during which a patient had an ICD-9/10 code for AML remission. The 6 months prior to the index date was defined as the baseline period. Post-remission therapy was divided into an early post-remission period, which included any therapy initiated within the first 60 days (≤ 60 d) after end of induction, and a late post-remission period, which included therapy initiated more than 60 days (> 60 d) after end of induction. If specific treatment information was available, late post-remission therapy was defined by a treatment switch occurring > 60 d after end of induction. Post-remission therapy ended at the earliest of relapse or end of follow-up (i.e., death, end of eligibility, or end of available data [December 31, 2016]). The post-relapse period was from the date of first AML relapse ICD-9/10 code after remission to the end of follow-up. Baseline patient characteristics, as well as HCRU and costs (adjusted to 2019 US dollars) during the baseline, induction, post-remission, and post-relapse periods, were summarized descriptively. HCRU and costs associated with induction and post-remission therapy periods were assessed during days that were part of a treatment cycle. The average per patient per month (PPPM) HCRU and costs were reported. Duration of response (DoR) from the first remission to the earliest of relapse or death was estimated using Kaplan-Meier analysis. Results: A total of 530 patients were identified. The median age at AML diagnosis was 73 years, 53.6% of patients were male, and 80.6% were white. The median time from index date to the end of follow-up was 13.5 months. Most patients received therapy with hypomethylating agents during the AML treatment. A total of 31.9% of patients who achieved remission did not receive post-remission therapy during follow-up; for these patients, mean (median) time from end of induction to relapse or end of follow-up was 125 (23) days. A total of 63.2% of patients received chemotherapy in the early post-remission period, and 43.0% of all patients went on to receive chemotherapy in the late post-remission period. The median DoR was 5.8 months; a total of 48.9% of patients had relapsed and 80.2% had died by the end of follow-up. The mean PPPM healthcare costs were highest for induction, followed by post-relapse, early post-remission, and late post-remission periods (Table). Costs associated with the inpatient (IP) setting were the greatest contributor to PPPM costs across all periods. IP visits were most common during induction with 92.1% of patients having ≥ 1 IP visit, relative to 53.8% during baseline, 65.7% during early post-remission, 71.5% during late post-remission, and 91.1% post-relapse. Conclusions: The economic burden of relapse is approximately 1.2 and 1.6 times higher than the mean PPPM healthcare costs during early and late post-remission periods, respectively. There exists a large unmet need for therapies that will extend the duration of the post-remission period and reduce the overall economic burden of AML. Disclosures Tabah: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Huggar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Karyopharm Therapeutics: Current equity holder in publicly-traded company; FibroGen: Current equity holder in publicly-traded company. Huey:Bristol Myers Squibb: Current Employment. Copher:Bristol Myers Squibb: Current Employment. Zhou:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Zichlin:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Koenigsberg:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Brunner:Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; AstraZeneca: Research Funding; Forty-Seven Inc: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Context AML is a malignant bone marrow cancer with substantial economic burden and poor prognosis. Remission rates in AML are 40–70% and most patients relapse. AML is associated with high healthcare resource utilization (HCRU), but this burden is understudied. Objective To assess the HCRU and costs associated with AML following relapse. Design A retrospective analysis of the IBM® MarketScan® Commercial and Medicare Supplemental Claims database, from January 1, 2012 to December 31, 2018, identified newly diagnosed AML patients (ICD-10-CM codes: 205.00, C92.00, C92.60, C92.A0) who received frontline therapy and no hematopoietic stem cell transplantation. Patients were continuously enrolled in medical and pharmacy benefits for ≥6 months prior to the AML diagnosis date (index date) and for a variable period post-index date; patients were followed until the earliest date of end of continuous enrollment, death, or end of study. Remission was identified by diagnosis codes and relapse was identified by diagnosis codes and treatment-based proxy. Main outcome measures HCRU and costs were analyzed descriptively. Results Of 1,558 patients identified, median age at diagnosis was 62.0 years and median follow-up was 232 days. Less than half of patients achieved remission (45.6%), of which 37.6% relapsed. Median time to relapse from start of frontline therapy was 168 days. Following relapse, mean total all-cause per patient healthcare cost was $282,360 (SD $417,931). 85.8% of patients had an inpatient admission with a per patient mean of 2.3 admissions and cost of $188,264 (SD $367,441). 47.2% of patients had ER visits with a per patient mean of 1.4 visits and cost of $1,573 (SD $3,603). 93.3% of patients had outpatient hospital services and 76.0% had office visits, with a per patient mean of 192.2 services and 12.5 visits, and costs of $63,291 (SD $107,952) and $1,785 (SD $2,964), respectively. Similar trends were observed for AML-related HCRU and costs. Conclusions This study demonstrates the economic burden associated with AML relapse. This burden is driven by inpatient admissions, which account for 67% of total all-cause cost. There remains an unmet need for novel treatments to delay relapse and reduce healthcare costs in AML patients. The study was supported by Bristol Myers Squibb.

Context AML is the most common form of acute leukemia in adults. The age-adjusted incidence of AML in the USA is 4.3/100,000 people, with median age of 68 years at diagnosis. Following diagnosis, treatment options include intensive induction chemotherapy to induce remission (followed by post-remission therapies, including high-dose cytarabine-based regimens and hematopoietic stem cell transplantation), less intensive induction treatment, or supportive care. Prognosis following relapse is poor, with median survival of 8–10 months; studies show much of this time is spent in inpatient or outpatient settings. Objective To examine HCRU, particularly inpatient hospitalizations and associated costs, in relapsed AML patients. Design A retrospective analysis was conducted using the Premier Healthcare Database, a hospital administrative database containing >1 billion inpatient and outpatient encounters in the USA. ICD-10-CM codes for AML in relapse-identified adult patients enrolled in the database between January 1, 2016 and March 31, 2019. The index date was the first relapse encounter date. Patients Patients were followed until inpatient death, or last inpatient discharge date/hospital-based outpatient visit, before the end of study period (September 30, 2019). Main outcome measures Demographics, comorbidities, inpatient and intensive care unit (ICU) admissions, length of stay (LOS), and costs. Results 2,290 patients were identified; mean age was 61.2 years (median 65.0) and 46.9% were female. Primary insurance coverage was Medicare (51.2%), commercial (29.1%), Medicaid (13.8%), or other (5.9%). Common comorbidities were diabetes (31.0%), chronic heart failure (19.5%), and chronic obstructive pulmonary disease (19.0%). Patient follow-up varied from Conclusions The results demonstrate the substantial HCRU burden and costs shouldered by patients and payers following diagnosis of relapsed AML. Though not assessed here, there is potential value in therapies that delay relapse and improve survival in AML patients. The study was supported by Bristol-Myers Squibb.

e19337 Background: In clinical trials, POM has demonstrated favorable clinical outcomes in patients with multiple myeloma (MM) who received prior LEN. Few studies, however, have examined POM treatment for MM in the community oncology setting. This retrospective cohort study compared treatment patterns and outcomes between patients who received a post-LEN treatment, either POM or another antimyeloma regimen. Methods: Adult patients with MM in the US Oncology Network (USON) who initiated a post-LEN treatment within 60 days of LEN discontinuation between Jan 1, 2016 and May 1, 2018, were not clinical trial participants, and had ≥ 2 subsequent clinic visits, were eligible. Data were sourced from USON’s iKnowMed electronic health records. Among patients observed to have discontinued treatment, time to treatment discontinuation (TTTD) was estimated from date of initiation of post-LEN treatment (index treatment) to date of discontinuation. Among patients who started a new treatment after the index treatment, time to next treatment (TTNT) was estimated from date of initiation of index treatment until date of initiation of the next treatment. TTTD and TTNT were analyzed using the Kaplan–Meier (KM) method across the whole study sample; patients who did not discontinue or start a next treatment were censored. Results: Of 547 eligible patients, 155 (28.3%) initiated POM and 392 (71.7%) initiated another antimyeloma regimen. Demographic characteristics were similar between the groups (for all patients, median age was 68 years, 54.5% patients were male and 71.7% were white). In total, 74.2% and 83.7% of patients discontinued the index treatment in the POM and other-treatment groups, respectively. Among the entire study population, KM estimates of median TTTD were 3.5 months (95% CI 2.8–4.6) and 1.9 months (95% CI 1.6–2.4) in the POM and other-treatment group, respectively (log-rank P < 0.001). In total, 65.2% and 71.2% of patients initiated subsequent treatment in the POM and other-treatment groups, respectively. KM estimates of median TTNT were 6.2 months (95% CI 4.5–7.8) and 4.5 months (95% CI 3.9–5.3) in the POM and other-treatment groups, respectively (log-rank P = 0.38). Conclusions: For patients with MM the use of POM following LEN treatment resulted in longer TTNT and TTTD compared with those who received other antimyeloma therapy. These findings support the use of POM treatment after LEN as an option for patients with relapsed/refractory MM.

e19539 Background: MF is an aggressive myeloid neoplasm and until recently RUX was the only treatment available. Real-world, long-term outcomes in pts with MF have not been described. Methods: Providers from multiple community oncology clinics in the USA reviewed the charts of consecutive pts with MF (primary or post-polycythemia vera/essential thombocythemia MF) who received RUX at any time from Jan 1, 2015 to Dec 31, 2017; data were collected Nov 15–26, 2019. Pt characteristics, treatment patterns, and outcomes (symptoms, blood counts, disease transformation) were retrospectively abstracted into an electronic case report form (eCRF) at each visit during the first 6 months, at any RUX dose modification; and at 12, 24, and 36 months post-RUX initiation. Pt characteristics, treatment patterns, rationale for dose modification, and treatment duration are described for pts during the first 6 months of therapy. Results: eCRFs were completed for 104 pts with MF treated with RUX. 42 pts received a RUX dose modification and 62 did not. Median follow-up from RUX initiation was 23.5 months. In the first 6 months of therapy, 40.4% of pts had a RUX dose modification (76.2% dose reduced; 23.8% dose increased). The most common reason (70%) for dose increase was titration to therapeutic dose. The most common reason (75%) for dose reduction was hemoglobin 8–10 g/dL or platelet count 50–75 × 109. The starting dose of RUX was higher for no RUX dose modification pts (mean total daily dose 34.9 mg vs 27.0 mg, P < 0.01). RUX dose-modified pts were older vs pts with no RUX dose modification ( P = 0.01); International Prognostic Scoring System (IPSS) risk score ( P = 0.89) and the proportion of pts with primary MF ( P = 0.06) were similar (Table). Overall, 64.4% of RUX treated pts discontinued therapy (RUX dose-modified 78.6%; no RUX dose modification 54.8%, P = 0.01). Median duration of RUX treatment was 11.0 months (RUX dose modified 10.6 months; no RUX dose modification 12.2 months; log rank P = 0.12). Conclusions: In this real-world study, 64.4% of pts discontinued RUX during follow-up. Higher rates of discontinuation and shorter time to discontinuation were noted for pts with a dose modification during the first 6 months of therapy. Given the short duration of therapy observed in this study as compared with published clinical trials, additional MF treatments are needed that offer pt benefit. [Table: see text]

e19336 Background: For pts with AML, prognosis is poor as long-term remission is elusive and ≥ 60% of pts relapse. The effect of remission status on healthcare resource utilization (HCRU) and costs is unclear. This study assessed administrative claims data from pts with AML to understand the potential benefit of novel, remission-prolonging therapies on HCRU and costs. Methods: Pts with newly diagnosed AML who received frontline therapy and did not undergo hematopoietic stem cell transplantation were identified in the MarketScan Commercial and Medicare Supplemental database from Jan 1, 2012–June 6, 2018. Pts were followed over a fixed 6-month (mos) pre- and variable post-diagnosis period; remission and relapse events were identified by diagnosis codes. Pts were analyzed by duration of remission ( < 3, 3– < 6, 6– < 9, and ≥ 9 mos), based on time from first remission claim to first relapse claim or end of follow up, whichever occurred first. Pt characteristics, relapse, HCRU, and costs were assessed. Results: 459/1003 eligible pts (45.8%) had evidence of remission. Most pts were in remission for < 3 mos (n = 161; 35.1%) or ≥ 9 mos (n = 165; 35.9%); 81 (17.6%) and 52 (11.3%) pts were in remission for 3– < 6 and 6– < 9 mos, respectively. Median follow-up for all pts was 236 days. Across remission cohorts, mean age at diagnosis was 55–59 years and median time to remission (from first AML diagnosis to first remission claim) was 82–90 days. Median time from AML diagnosis to relapse was 265.5 days. Of pts in remission, 30.5% relapsed (41.0%, 28.4%, 40.4%, and 18.2% for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively). From AML diagnosis to the end of follow-up, mean all-cause per pt per mos (PPPM) healthcare costs for all pts were $44,588. Longer durations of remission were associated with reduced mean PPPM costs ($64,188, $53,260, $30,219, and $16,654 for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively); similar trends were observed for AML-related costs. Mean all-cause PPPM costs were also reduced during remission, measured from the first remission claim to the first relapse claim or end of follow-up. A significant decrease was observed for pts in remission for ≥ 6 mos ($35,229, $36,193, $17,486, and $8,933 for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively). Conclusions: In this real-world study, 46% of pts with AML achieved remission after frontline therapy, although durations of remission varied. A longer duration of remission was associated with reduced PPPM costs over the study period indicating a potential economic benefit of remission-prolonging therapies in AML, including maintenance treatments.

Background Lenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan. Methods A partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts. Results For lenvatinib versus sorafenib, the incremental cost was − 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer’s willingness-to-pay-per-QALY of 5 million JPY. Conclusions Lenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan. Electronic supplementary material The online version of this article (10.1007/s00535-019-01554-0) contains supplementary material, which is available to authorized users.

Introduction Real‐world data are critical to demonstrate the consistency of evidence and external generalizability of randomized controlled trials (RCTs). This study examined characteristics and outcomes of metastatic triple‐negative breast cancer (mTNBC) patients treated with eribulin mesylate at community oncology practices in the United States. Methods Physicians identified mTNBC patients initiating eribulin between 1 January 2011 and 1 January 2014 and abstracted data into an electronic case report form (eCRF). Eribulin treatment in the metastatic setting was categorized as early use (EU, first‐/second‐line) and late use (LU, third‐line or later). Patient characteristics, overall survival (OS), disease response (per treating physician), and adverse events (AEs) rates in each group, respectively, are reported. Results Overall 252 eCRFs were completed: 125 (49.6%) EU and 127 (50.4%) LU. The median age at metastatic diagnosis was 53 years and 42.1% were stage IV at their initial diagnosis. The median duration of follow‐up from the initiation of first‐line treatment was 24 months. Rates of disease response (complete or partial per treating physician) were 69.9% in the EU group and 48.8% in the LU group. The five most commonly reported adverse events during eribulin were as follows: fatigue (65.1%), weakness (40.1%), decreased appetite (32.5%), neutropenia (31.0%), and leukopenia (27.4%). Discontinuation of eribulin due to AE was observed in 4.0% of patients. Median OS from initiation of eribulin was 23.0 months (95% CI: 18.7‐27.3) among EU and 14.7 (95% CI: 12.6‐16.9) among LU. Conclusion In the real‐world eribulin‐treated mTNBC, patients have more sites of metastatic disease and exposure to greater numbers of prior therapies compared to RCTs. The median OS of 14.7 months among LU patients is consistent with, and slightly longer than the 13.1 months and 14.4 months reported in the EMBRACE and Study 301 clinical trials, respectively.

Aim: For dichotomous outcomes, odds ratio (OR) is one of the usual summary measures of indirect treatment comparison. A corresponding number needed to treat (NNT) estimate may facilitate understanding of the treatment effect. Methods: We show how to estimate NNT based on OR results of a matching adjusted indirect comparison. We also have derived the explicit formula of its 95% CIs by applying the delta method, and as an alternative, a simulation-based method. Results: The method was applied in a case study example in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients, comparing lenvatinib to sorafenib. For every two RR-DTC patients treated with lenvatinib instead of sorafenib, one fewer would have progressed and for every eight RR-DTC patients treated with lenvatinib instead of sorafenib, one fewer would have died. Conclusion: Using NNT to summarize the results of a matching adjusted indirect comparison can help the clinicians to better understand the results in addition to OR.

Epilepsy adversely affects childhood development, possibly leading to increased economic burden in pediatric populations. We compared annual healthcare utilization and costs between children (12 years old) with stable and uncontrolled epilepsy treated with antiepileptic drugs (AEDs).Children (12 years old) with epilepsy (ICD-9-CM 345.xx or 780.39) in 2008 were identified in the MarketScan claims database from 2007 to 2009. Patients with "stable" epilepsy used the same AED for ≥12 months, and patients with "uncontrolled" epilepsy were prescribed additional AED(s) during that period. For patients with uncontrolled epilepsy, the study index date was the start of additional AED(s); for patients with stable epilepsy, the study index date was a random AED fill date. Epilepsy-related utilization included medical services with 345.xx or 780.39 in any diagnosis field and AED fills. Epilepsy-related costs included AEDs, medical claims with epilepsy in any diagnosis field, and certain tests. We adjusted for baseline cohort differences (demographics, region, usual-care physician specialty, and comorbidities) using logistic regression and analysis of covariance.Two thousand one hundred seventy patients were identified (mean: 7.5 years; 45.3% were female; Charlson comorbidity index: 0.3; 422 (19.4%) patients with uncontrolled epilepsy). Patients with uncontrolled epilepsy faced more hospitalizations (30.1% vs. 12.0%) and greater overall ($30,343 vs. $18,206) and epilepsy-related costs ($16,894 vs. $7979) (all p.001). Adjusting for baseline measures, patients with uncontrolled epilepsy had greater odds of hospitalization (OR: 2.5; 95% CI: 1.9-3.3) and costs (overall: $3908, p=.087; epilepsy-related: $5744, p.001).Children with uncontrolled epilepsy use significantly more healthcare resources and have a greater economic burden than children with stable epilepsy. However, epilepsy accounted for only half of overall costs, indicating that comorbid conditions may add substantially to the disease burden.

Despite the availability of numerous antiepileptic drugs (AEDs), some epilepsies remain resistant to treatment. We compared utilization and costs in patients with uncontrolled epilepsy to those with stable epilepsy. Claims data (2007-2009) were used to identify adults with epilepsy requiring additional AED therapy (having uncontrolled epilepsy) and those not requiring additional AED therapy (having stable epilepsy). The date in 2008 on which an additional AED was started was the index date for patients with uncontrolled epilepsy, and a randomly selected date was used for patients with stable epilepsy, whose AED use was unchanged in the preceding year. In the postindex year, all pharmacy and medical claims were used to estimate overall utilization and costs; claims with epilepsy in any diagnosis field were used to estimate epilepsy-related outcomes. Outcomes were adjusted using multivariate analyses. We identified 1536 patients with uncontrolled epilepsy and 8571 patients with stable epilepsy (mean age: 42.8years; female: 48%). Patients with uncontrolled epilepsy had higher comorbidity rates (p

Background: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, cytopenias, and poor survival. Ruxolitinib (RUX) is the only approved treatment for Intermediate or High-risk MF. In a previous study, we have shown almost 1 in 3 patients initiating RUX had dose modifications during the first 3 months of treatment (Burton T et al. HemaSphere 2019). The objective of this study was to assess RUX treatment patterns among patients with MF. Methods: This retrospective analysis used administrative claims data from a large US health plan to identify adults (aged ≥ 18 years) with ≥ 1 claim for RUX and ≥ 2 non-diagnostic medical claims for primary (International Classification of Diseases [ICD] 9th or 10th Revision [9/10]: 238.76, D47.4) or secondary MF (ICD-9/10: 289.83, D75.81) from January 1, 2012 to June 30, 2018. The first RUX claim on or after the first MF claim defined the index date. Included patients were continuously enrolled in a commercial or Medicare Advantage health plan for 3 months before the index date (pre-index period) and 6 months on or after the index date (post-index period). Clinical characteristics, MF-related treatments, health care resource utilization (HCRU), and costs were assessed during the pre- and post-index periods. Costs were adjusted to 2018 US dollars using the medical component of the Consumer Price Index. Cohorts were created based on the maximum (max) RUX daily dose observed during the 6-month post-index period: suboptimal max < 30 mg/day (SUB); and optimal max ≥ 30 mg/day (OPT). All variables were analyzed descriptively. Results: Among 495 eligible patients, mean (SD) age was 69.4 (10.3) years; 54.1% were male; and 25% had a primary MF diagnosis code. Median initial RUX dose was 30 mg/day and patients continued with this dose for a mean (SD) of 70.0 (45.8) days. RUX dose was modified for 19.4% of patients during the 6-month post-index period, and the distribution of max RUX daily doses was: < 15 mg (13.7%), 15-29 mg (24.9%), 30-40 mg (55.8%), and > 40 mg (5.7%). Two groups based on max RUX dosing were further analyzed: 191 (38.6%) in the SUB cohort (< 30 mg), and 304 (61.4%) in the OPT cohort (≥ 30 mg). Patients in the SUB cohort were older than patients in the OPT cohort (SUB: mean 70.8 [SD 10.1] years; OPT: mean 68.5 [SD 10.3] years; P = 0.013), but the mean Charlson Comorbidity Index scores did not differ (SUB: mean 1.6 [SD 1.8]; OPT: mean 1.5 [SD 1.8]; P = 0.601). Rates of anemia were higher at baseline for the SUB cohort than the OPT cohort (SUB: 64.9%; OPT: 53%; P = 0.009). During the 6-month post-index period, compared with patients in the OPT cohort, patients in the SUB cohort had a higher proportion of thrombocytopenia (SUB: 31.4%; OPT: 22.7%; P = 0.03). Nearly half (45.5%) the sample used a supportive agent such as an androgen, systemic steroid, or erythropoiesis-stimulating agent during the post-index period (SUB: 48.2%; OPT: 43.8%; P = 0.34). With respect to HCRU and costs, the SUB cohort had a higher proportion of emergency department (ED) visits than the OPT cohort during baseline (SUB: 31.4%; OPT: 23.4%; P = 0.048); and baseline total mean (SD) all-cause costs were USD 18,079 (21,876) overall, USD 18,908 (24,411) for the SUB cohort, and USD 17,559 (20,145) for the OPT cohort (P = 0.523). During the 6-month follow-up period, 31.1% of patients had ≥ 1 ED visit (SUB: 35.1%; OPT: 28.6%; P = 0.131), 22.8% had ≥ 1 inpatient (IP) hospitalization (SUB: 24.6%; OPT: 21.7%; P = 0.455), and total mean (SD) all-cause costs were USD 94,498 (97,391) overall (SUB: USD 93,289 [115,418]; OPT: USD 95,258 [84,315]; P = 0.839). Conclusion: In this study, patients with MF treated with RUX experienced significant disease burden and high costs, regardless of dose. Both anemia and thrombocytopenia were observed along with nearly half of patients using a supportive agent. Given the large proportion of patients with a dose adjustment, suboptimal dosing, and an IP hospitalization, there continues to be a need for additional therapeutic options for patients with MF. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership. Patel:Celgene Corporation: Employment, Equity Ownership. Sundquist:Optum: Employment, Equity Ownership. Lal:Optum: Employment. Copher:Celgene Corporation: Employment. Gerds:Roche: Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding; CTI Biopharma: Consultancy, Research Funding; Imago Biosciences: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy.

Introduction: β-thalassemia is a genetic blood disease characterized by ineffective erythropoiesis due to defective hemoglobin production that manifests as potentially fatal anemia. Patients with β-thalassemia rely on regular, lifelong red blood cell transfusions (RBCTs) for survival and suffer from multi-system complications, physical manifestations, and decreased health-related quality of life (HRQoL) due to iron overload and continual RBCTs. This literature review aims to describe the disease burden associated with β-thalassemia. Methods: Electronic databases (MEDLINE®, Embase®, Cochrane Library) were searched to identify articles in the English language assessing the clinical, economic, and humanistic burden of β-thalassemia in North America and Europe. Articles were selected based on predefined criteria including appropriate study design, disease state, country, and outcome measures. Results: Patients with β-thalassemia who received regular RBCTs were significantly more likely to develop ≥ 1 iron overload-related comorbidity than matched, non-thalassemia controls (P < 0.0001). Other iron-related issues included cardiac disease (observed in 13-30% of patients), hypogonadism (17-22%), diabetes (10-18%), osteoporosis (16%), hypothyroidism (12%), liver disease (4%), and hypoparathyroidism (2%). RBCTs also introduced the risk of transfusion reactions (48-50%), infections (24-65%), and development of alloantibodies (19-23%). Mortality rate for the US population was 1.9%. The direct annual cost per regularly transfused patient with β-thalassemia was significantly higher than in matched controls (USD 128,062 vs USD 5,438; P < 0.001; 2016 USD). The main annual cost drivers per patient were iron chelation therapy (48%; USD 61,974) and RBCTs (31%; USD 39,723). Indirect costs for β-thalassemia were impacted by unemployment, reported at 33% among patients with β-thalassemia versus 24% for the general US population. Patients scored significantly worse on 5 subdomains (physical functioning, role-physical, general health, social functioning, and role-emotional) of the Short Form-36 (SF-36) HRQoL questionnaire compared with the general US population (all P < 0.0001) with the greatest impairments seen in the general health subdomain (P < 0.0001). Clinically meaningful reductions in physical functioning, role-physical, and general health scores were observed for patients with β-thalassemia aged < 65 years with transfusion-related iron overload. Bodily pain was reported by 56-69% of patients with β-thalassemia, and pain interfered with patient physical and emotional functioning HRQoL outcomes. Increasing age correlated with higher numbers of pain responses (P < 0.001). Psychiatric comorbidities were found in 24% of patients with β-thalassemia, and mood disorders, including depression and anxiety, were associated with overall significantly poorer physical and mental HRQoL (P < 0.001). Conclusions: β-thalassemia is associated with a substantial clinical, economic, and humanistic burden in the USA. Patients with β-thalassemia experience reduced life expectancy, significant comorbidities, considerable direct healthcare costs, unemployment, and impaired HRQoL. There is a need for more effective management and therapeutic options for these patients. Disclosures Mearns: Celgene Corporation: Employment. Udeze:Celgene Corporation: Employment. Copher:Celgene Corporation: Employment. Sheth:CRSPR/Vertex: Other: Clinical Trial Steering committee; Apopharma: Other: Clinical trial DSMB; Celgene: Consultancy.

Introduction: Symptomatic anemia transfusion support represents a significant problem for patients with MDS. The principal strategy in managing these patients remains supportive care with erythropoiesis-stimulating agents (ESAs) and red blood cell (RBC) transfusions. However, there is paucity of real-world data regarding patterns of use of ESA and other therapies, and its impact on transfusion needs in these patients early in their clinical course. To address this question, we performed a retrospective claims-based study to characterize treatment patterns and transfusion burden in patients with MDS. Methods: In this retrospective claims analysis of a large national health insurance plan, all patients aged ≥ 18 years with newly diagnosed MDS (≥ 2 medical claims with an International Classification of Diseases, 9th or 10th Revision [ICD-9 or ICD-10] diagnosis codes ≥ 30 days apart) identified between January 2012 and May 2018 were included. Index date was defined as date of first diagnosis. Continuous health plan enrollment for ≥ 6 months pre- and 3 months post-index date was required. RBC transfusion status was evaluated during the 16 weeks prior to first diagnosis as well as 16 weeks prior to and immediately following line of therapy (LOT) 1 and LOT2. Transfusion burden categories were adapted and modified from the proposed International Working Group 2018 revised criteria (Platzbecker U, et al., Blood. 2019;133(10):1096-1107). Categories included transfusion independence (TI), defined as patients receiving no transfusions during the observation period; low (LTB), moderate (MTB), and high transfusion burden (HTB) were defined by patient's having 1-3, 4-7, and ≥ 8 unique dates for a transfusion during the observation periods, respectively. Therapies in each LOT were captured using pharmacy and medical claims data. The end of a LOT was defined after ≥ 60-day gap in therapy, a claim for any new or additional MDS therapy, or patient death; LOT durations are described for non-censored patients. Results: Among the 3,587 patients identified (mean age = 74.9 years, 44.3% female), transfusion burden during 16 weeks prior to index was: 78.8% TI, 19.2% LTB, 1.9% MTB, and 0.2% HTB. Among the 1,935 patients who received LOT1, transfusion burden in the 16 weeks preceding LOT1 was: 57.0% TI, 36.3% LTB, 5.6% MTB, and 1.1% HTB. The top 5 regimens in LOT1 were ESA monotherapy (61.9%), hypomethylating agent (HMA) monotherapy (19.2%), white blood cell growth factor (WBCGF) monotherapy (3.5%), immunomodulators (3.3%), and HMA + ESA (2.7%) (Figure). Of 824 patients who received LOT2, transfusion burden prior to LOT2 was: 49.4% TI, 28.6% LTB, 16.5% MTB, and 5.5% HTB. The top 5 regimens in LOT2 were ESA monotherapy (44.2%), HMA monotherapy (12.1%), HMA + ESA (9.2%), WBCGF + ESA (6.9%), and WBCGF monotherapy (6.4%) (Figure). In LOT1, the median treatment duration for ESA monotherapy was 2.8 months (mean = 5.2 months, standard deviation [SD] = 6.8) whereas in LOT2, the median treatment duration was 2.0 months (mean = 3.7 months, SD = 5.0). Amongst patients receiving ESA monotherapy as LOT2, 90.4% had prior ESA monotherapy as LOT1. In patients treated with HMA monotherapy in LOT1 that also experienced a LOT2, 39.1% moved on to a variety of LOT2 regimens (Table), while in 15.5% ESAs were combined with HMA (Table). Conclusions: Our results show that at the time of diagnosis, 20% of MDS patients were transfusion dependent, but up to 50% require treatment. The high rate of ESA use is likely due to anemia-related symptoms. In those treated with ESA monotherapy, approximately 50% have a LOT1 duration that is < 3 months, and interestingly, the majority of patients restart a second LOT with an ESA as the most common regimen. Additional analyses are necessary to determine whether this indicates a switch in ESA agent, escalation in dose of prior ESA, treatment cycling due to elevated hemoglobin, or other reasons. Considering the short median treatment duration and worsening of transfusion dependency beyond first line, there remains a high unmet need for MDS therapy that more effectively slows the progression of transfusion dependence. Disclosures Mukherjee: Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor. Slabaugh:Celgene Corporation: Employment, Equity Ownership. Copher:Celgene Corporation: Employment. Johnson:Optum: Employment; Celgene Corporation: Consultancy. Buzinec:Optum: Employment. Mearns:Celgene Corporation: Employment.

To describe treatment patterns and healthcare burden among individuals with suspected pulmonary arterial hypertension (PAH), as identified through a practice guideline-based healthcare claims algorithm.Adults with evidence of PAH from 1 January 2004 (commercial and Medicaid) or 1 July 2006 (Medicare Advantage) through 30 June 2008 were identified. Given the lack of an ICD-9 code for PAH, an algorithm was developed requiring: (1) ≥ 1 claim for PAH medication (index date); (2) ≥ 1 claim with a pulmonary hypertension diagnosis code in the 6-month pre-index period (baseline) or within 90 days post-index; (3) a right heart catheterization or pulmonary hypertension-related inpatient stay during baseline or within 90 days post-index; and (4) continuous health plan enrollment for 6 months pre-index and ≥ 6 months post-index. Patients with PAH-specific medications during baseline were excluded. Treatment patterns, healthcare utilization, and costs were assessed during the period ending with the earlier of health plan disenrollment or 31 December 2008.Among the 521 included patients, 69% were female. Most patients (94%) initiated treatment with monotherapy (most commonly sildenafil or bosentan), and 12.7% of all patients augmented their therapy by the end of the observation period. The medication possession ratio was 0.96 each for ambrisentan (SD=0.04), bosentan (SD=0.04), and sildenafil (SD=0.05). Overall, 72.6% of patients discontinued therapy with a mean of 149 (SD=170) days until discontinuation. A mean (SD) of 2.14 (1.82) all-cause office and 1.64 (1.98) outpatient visits occurred per patient per month. Mean PAH-related healthcare costs were $6617 per patient per month, comprising 71% of all-cause costs. The guideline-based algorithm may not have perfectly captured patients with PAH.Patients with suspected PAH were likely to initiate treatment with oral monotherapy, had high compliance rates, and received close ambulatory follow-up. PAH-related costs constituted the majority of all-cause healthcare costs.

e16550Background: Targeted therapy is widely used as 1st and 2nd line treatment in metastatic renal cell carcinoma (mRCC). This study assessed the impact of disease progression (DP) on patient repo...