All-cause Research Articles

Sleep duration and mortality among breast cancer survivors in the Western New York Exposures and Breast Cancer (WEB) Study.

There is increasing evidence that sleep duration may affect breast cancer survival through effects on circadian function, influencing disease progression. However, further investigation of this association is needed. In a population-based, prospective cohort study of women from the Western New York Exposures and Breast Cancer Study, we examined mortality outcomes with invasive breast cancer identified using the National Death Index. Cox proportion hazards ratios with 95% confidence intervals were used to estimate risk of all-cause (AC) and breast cancer-specific (BC) mortality associated with self-reported usual sleep duration with adjustment for age, race/ethnicity, years of education, body mass index (BMI), menopausal status, pack-years ofsmoking, tumor stage, and estrogen-receptor (ER) status. We further examined associations within strata of BMI, tumor stage, menopausal status, and ER status. A sample of 817 patients with breast cancer were followed for a median of 18.7years, during which 339 deaths were reported, including 132 breast cancer-specific deaths. Those who reported shorter or longer sleep tended to have a slightly higher BMI, to be less proportionately non-Hispanic White, to report a previous history of benign breast disease, and to have consumed more alcohol during their lifetime. We found no significant associations between sleep duration and AC or BC mortality, including within stratified analyses. Sleep duration was not associated with either AC or BC mortality including within strata of BMI, tumor stage, menopausal status, or ER status.

Maintenance, withdrawal, and re-treatment with ritlecitinib and brepocitinib in patients with alopecia areata in a single-blind extension of a phase 2a randomized clinical trial

Maintenance, withdrawal, and re-treatment with ritlecitinib and brepocitinib in patients with alopecia areata in a single-blind extension of a phase 2a randomized clinical trial

Do dietary patterns influence survival in hemodialysis patients?

Rationale: Nutritional recommendations for hemodialysis (HD) patients focus on achieving sufficient energy and protein without exceeding phosphorus, potassium, sodium and fluids intake. We aimed to identify dietary patterns (DP) and analyze their relationship with all-cause (AC) and cardiovascular (CV) mortality in HD patients.

808-P: Economic Benefits of Initiating Empagliflozin vs. GLP-1 Receptor Agonists among Patients with Type 2 Diabetes

Background: SGLT-2 inhibitors and GLP-1 receptor agonists (GLP-1RAs) have proven clinical benefit profiles, and the ADA recommends both as treatment options for T2D patients uncontrolled on metformin. There is limited research on whether these clinical benefits translate into differential cost savings. This study sought to assess the all-cause (AC) healthcare costs associated with initiating empagliflozin (EMPA) vs. GLP-1RAs among patients with T2D. Methods: A commercial US claims database was used to identify patients with T2D who newly initiated EMPA or GLP-1 RA from 08/2014-09/2018. Study cohorts (EMPA users and GLP-1RA users) were matched using propensity scores (PSs) (1:1 ratio, caliper: ± 0.05) based on baseline demographic and clinical variables. AC costs were computed on a per patient per month (PPPM) basis during a variable follow-up period of up to 12 months and compared across study cohorts using generalized linear models. A subanalysis comparing AC costs among patients who initiated second-line treatment with EMPA or GLP-1RA after metformin monotherapy was also conducted. Results: PS matching resulted in a sample of 43,588 patients (21,794 patients in each group) whose mean age was 54 years and 63% were male. The total AC PPPM costs were significantly lower for EMPA vs. GLP-1RA users ($1,450 vs. $1,723; Δ = $273; P<0.001), with both pharmacy (Δ = $195; P<0.001) and medical (Δ = $78; P=0.006) costs being significantly lower. Similar results were observed in the subanalysis where initiating EMPA after metformin monotherapy was associated with lower AC PPPM costs compared to GLP-1RA users (Δ = $271; P<0.001). Conclusion: Among patients with T2D, initiating EMPA vs. GLP-1RA was associated with lower AC healthcare costs, where the drivers were both lower medical and pharmacy costs. These findings can inform treatment selection processes that are aimed to optimize T2D management, especially from an economic perspective. Disclosure P. Pimple: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. A. Raju: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Takeda Pharmaceutical Company Limited, Employee; Self; Xcenda LLC, Stock/Shareholder; Self; Teva Pharmaceutical Industries Ltd. E. Farrelly: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Takeda Pharmaceutical Company Limited, Employee; Self; Xcenda LLC. S. Shetty: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Funding Boehringer Ingelheim

The Incremental Burden of Atrial Fibrillation and Heart Failure: A Real-world Claims-based Analysis

Background Atrial fibrillation (AF) and heart failure (HF) are independent and growing problems in the United States, representing a significant clinical and economic burden to the healthcare system. While the strong association between AF and HF - due to common risk factors and the ability of each condition to cause the other - has been extensively characterized, the clinical and economic burden of comorbid AF and HF is not fully understood. This study characterizes the incremental health economic burden of patients with comorbid AF and HF. Methods This retrospective analysis leveraged United Healthcare's Optum claims database from January 2007 to June 2019. Patients were included if they had a minimum of 1 inpatient or 2 outpatient claims with a diagnosis of AF or 1 inpatient claim with a primary diagnosis of HF, were 18 years of age or older, and had no record of end stage renal disease, implanted cardiac device, or rheumatic heart failure. Patients were divided into three cohorts: (1) “AF,” patients with AF and no record of heart failure (N=(311,336); (2) “Comorbid,” patients with AF and a HF hospitalization (N=51,310); and (3) “HF Hosp,” patients with a heart failure hospitalization and no record of AF (N=47,469). Study outcomes included time to stroke/TIA (Kaplan Meier), average length of hospital stay, and annual rate of healthcare utilization post-index date [all-cause (AC) hospitalizations, HF hospitalizations, emergency department (ED) visits, outpatient (OP) visits, and home health visits]. Results Comorbid patients are older (77.4 years) and sicker (Elixhauser = 10.3) than AF Only and HF Hosp Only patients (AF: 68.6 years, Elixhauser= 5.1; HF Hosp: 70.3 years, Elixhauser=8.7). The comorbid cohort had a higher risk of stroke/TIA (51%) than AF Only (36%) and HF Hosp Only (43%) at 12 years (p Conclusions Comorbid AF and HF is associated with particularly poor clinical outcomes and a substantial health economic burden. Further, HF in the absence of AF also confers worse clinical outcomes and elevated healthcare use.

1152-P: Effect of Initiating Empagliflozin vs. Glucagon-Like Peptide-1 Receptor Agonists on Health-Care Costs among Patients with Type 2 Diabetes

The 2019 ADA’s Standards of Medical Care in Diabetes recommends use of SGLT2 inhibitor (SGLT2i) or GLP-1 receptor agonist (GLP-1RA) as one of the six drug classes after metformin (MET) in T2D patients, and is recommended as the treatment of choice among patients with cardiovascular disease (CVD; empagliflozin [EMPA] and liraglutide showing stronger evidence). To understand the economic impact of these recommendations, we evaluated the effect of EMPA vs. GLP-1 RA initiation on all-cause (AC) healthcare costs in patients with T2D. This retrospective cohort study utilized an U.S. commercial claims database to identify patients with T2D who newly initiated EMPA or a GLP-1RA between 08/2014 - 12/2016. First prescription date (index date) for EMPA or a GLP-1RA was used to classify patients into respective cohorts. T2D diagnosis and baseline covariates were assessed during 1-year pre-index period. During a post-index period of up to 1 year, AC costs were computed on a per patient per month (PPPM) basis; and evaluated using generalized linear models that controlled for pre-index covariates. Compared to the GLP-1RA cohort (N = 13,216), patients in the EMPA cohort (N= 3,857) were younger, more likely to be male, and had lower rates of obesity in the 1-year baseline period; all other measured pre-index covariates were similar. After covariate adjustment, the adjusted total AC PPPM cost difference ($1,137 vs. $1,370; difference (Δ) = -$233 PPPM) remained significantly lower for the EMPA cohort (P<0.001), as compared to GLP-1 RA cohort. Both medical (Δ = -$26 PPPM, p=0.06), and pharmacy (Δ = -$197 PPPM, p<0.001) costs were lower in EMPA cohort, as compared to GLP-1 RA cohort. Use of empagliflozin vs. GLP-1 RA in T2D patients was associated with lower all-cause healthcare costs. Together with ADA guidelines, these findings can aid health care stakeholders in treatment decisions and optimizing clinical and economic outcomes for patients with T2D. Disclosure P. Pimple: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Employee; Spouse/Partner; CVS Caremark. A. Raju: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb. D. Stafkey-Mailey: None. S. Shetty: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

Short-term impact of PM2.5, PM10, and PMc on mortality and morbidity in the agglomeration of Warsaw, Poland

The work presents the results of short-term health effects assessment of particulate matter (PM) in Warsaw, the capital of Poland. The influence of three PM fractions, PM10 (particles of aerodynamic diameter < 10 μm), PM2.5 (particles of aerodynamic diameter < 2.5 μm), and PMc (coarse fraction of diameter between 2.5 and 10 μm), modeled by the CALMET/CALPUFF system, has been studied in the period of 2013–2014. Six population health endpoints; daily counts of all-cause (ALL), cardiovascular (CV), and respiratory (RS) death cases; and ALL, CV, and RS hospital admissions were investigated with the use of statistical time series analysis via nonparametric generalized additive model (GAM) approach. The results show that PM2.5 increases the relative risk (RR) of ALL premature deaths by 0.7% per 10 μg/m3, as well as of CV mortality by 0.9%. PM10 exposures reveal the largest influence on mortality in a 2-day lag: 0.3% for all causes and 0.4% for CV causes, while for RS causes only in the elderly group (above 65 years, 1.4%) and for males (2.1%). The risk of hospitalizations increases with elevated PMc levels by 2.5%, 2.1%, and 4.6% for ALL, CV, and RS hospital admissions, respectively. The results suggest that the research on PM impact on health should concentrate more on attempts to assign specific health outcomes to PM originating from different types of sources, characterized by different granulation, as well as physical and chemical properties of emitted particles.

Abstract 232: Initiating Empagliflozin vs. Glucagon-like Peptide 1 Receptor Agonists is Associated With Lower Healthcare Cost of Care Among Patients With Type 2 Diabetes and Cardiovascular Disease

Background: The 2019 ADA’s Standards of Medical Care in Diabetes recommend use of SGLT-2 inhibitor (SGLT-2i) or GLP-1 receptor agonist (GLP-1RA) as one of the six drug classes after metformin (MET) in type 2 diabetes (T2D) patients, and is recommended as the treatment of choice among patients with cardiovascular disease (CVD; empagliflozin [EMPA] and liraglutide showing stronger evidence). CVD benefits of empagliflozin and GLP-1 RAs have been demonstrated in clinical trials; however, the impact on all-cause (AC) healthcare costs has not been studied. Methods: This retrospective cohort study utilized an US based, commercial claims database (IQVIA Pharmetrics Plus) to identify patients with T2D and CVD who initiated empagliflozin or a GLP-1 RA between 08/01/2014 - 12/31/2016. First prescription date (index date) for empagliflozin or a GLP-1 RA was used to classify patients into study cohorts. During a post-index period of up to 1 year, AC costs were computed on a per patient per month (PPPM) basis; and evaluated using generalized linear models that controlled for pre-index covariates. A sub-analysis comparing AC costs among patients who initiated second-line treatment with empagliflozin or a GLP-1 RA after metformin monotherapy, was also conducted. Results: As compared to the GLP-1 RA cohort (N = 1376), patients in the empagliflozin cohort (N= 441) were more likely to be males, had a lower Charlson comorbidity score, higher rates of dyslipidemia, and lower rates of obesity in the 1-year pre-index period; all other measured pre-index characteristics were similar. After covariate adjustment, compared to GLP-1 RA cohort, the empagliflozin cohort had lower total AC PPPM (($1,766 vs. $2,096; difference (Δ) = $330, p&lt;0.001 ), medical (Δ = $97, p=0.28 ), and pharmacy (Δ = $228, p&lt;0.001 ) costs. In patients who initiated 2 nd line empagliflozin or GLP-1 RA treatment, the empagliflozin cohort (N = 160) had lower total AC PPPM (($1,432 vs. $1,969; Δ = $536, p&lt;0.001 ), medical (Δ = $275, p=0.02 ), and pharmacy (Δ = $225, p=0.12 ) costs, compared to the GLP-1 RA cohort (N = 477). Conclusions: In patients diagnosed with T2D &amp; CVD, initiating empagliflozin compared to GLP-1 RA was associated with lower all-cause healthcare costs. Together with ADA guidelines, these findings can provide critical insights for health care decision makers for reducing the clinical and economic burden for patients with T2D &amp; CVD.

Progress (?) Toward Reducing Pediatric Readmissions.

Many children's hospitals are actively working to reduce readmissions to improve care and avoid financial penalties. We sought to determine if pediatric readmission rates have changed over time. We used data from 66 hospitals in the Inpatient Essentials Database including index hospitalizations from January, 2010 through June, 2016. Seven-day all cause (AC) and potentially preventable readmission (PPR) rates were calculated using 3M PPR software. Total and condition-specific quarterly AC and PPR rates were generated for each hospital and in aggregate. We included 4.52 million hospitalizations across all study years. Readmission rates did not vary over the study period. The median seven-day PPR rate across all quarters was 2.5% (range 2.1%-2.5%); the median seven-day AC rate across all quarters was 5.1% (range 4.3%-5.3%). Readmission rates for individual conditions fluctuated. Despite significant national efforts to reduce pediatric readmissions, both AC and PPR readmission rates have remained unchanged over six years.

Abstract 168: A Real-World Claims Analysis of Costs Among Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease Receiving Empagliflozin or Other Antihyperglycemic Agents

Background: Cardiovascular disease (CVD) is a major complication and the leading cause of death associated with type 2 diabetes (T2D). People with T2D are 2 to 4 times more likely to develop CVD than those without T2D. Empagliflozin, a novel SGLT-2 inhibitor, has demonstrated beneficial clinical effects on cardiovascular outcomes in both RCTs and real-world studies. The objective of this study was to evaluate total healthcare costs in patients initiating empagliflozin compared to other antihyperglycemic agents (AHAs; DPP-4 inhibitors, other SGLT-2 inhibitors [excluding empagliflozin], GLP-1 agonists, or insulin) in T2D patients with CVD. Methods: A retrospective cohort study was conducted using a US-based, commercial administrative claims database. Patients who were newly initiated on either empagliflozin or other AHAs between 08/01/2014-12/31/2016 were eligible for inclusion in the study as either an empagliflozin cohort or other AHAs cohort. The index date was the date of the first prescription for empagliflozin or other AHA. A 1-year pre-index period was used to identify patients with both CVD and T2D diagnosis and to assess covariates of interest. Patients were excluded if they had a claim for empagliflozin or other AHA during the pre-index period. All outcomes were assessed during a post-index period of up to 1 year. All-cause (AC) costs were computed on a per-patient-per-month (PPPM) basis and evaluated using generalized linear models, controlling for differences in pre-index characteristics between the 2 cohorts. Results: A total of 13,563 T2D patients with CVD met the study criteria (empagliflozin=441; other AHAs=13,122). The mean age±SD was 58±9 years, 69% were male, and atherosclerosis was the most common CVD. Compared to the other AHAs, patients in the empagliflozin cohort were younger and had fewer hospitalizations and lower AC costs in the pre-index period but were more likely to use other AHAs or CVD-related drugs and have dyslipidemia in the pre-index period. During the post-index period, unadjusted total PPPM AC costs were significantly lower for the empagliflozin cohort vs other AHAs ($1,690 vs $2,489; P &lt;0.001). After covariate adjustment, the adjusted total AC cost difference ($412 PPPM [$2,057 vs $2,469]) remained significantly lower for the empagliflozin cohort ( P &lt;0.001). The adjusted cost differences were mainly driven by lower AC medical costs for the empagliflozin cohort (cost difference: $400; P ≤0.001), as no significant difference in AC pharmacy costs were observed (cost difference: $31; P =0.554). Conclusions: In this study, patients diagnosed with T2D and CVD had lower all-cause costs following treatment initiation with empagliflozin compared to other AHAs. This finding can provide critical insight for healthcare decision makers tasked with reducing the clinical and economic burden associated with CVD among patients with T2D during therapy selection.

Estimated costs of grade 3–4 all-cause and treatment-related adverse events for stage IV or recurrent non-small cell lung cancer (NSCLC) in the CheckMate 227 (CM-227) trial.

120 Background: In the ongoing phase 3 CM-227 trial, nivolumab + ipilimumab (N+I) showed significantly longer progression-free survival compared to chemotherapy (C) among patients with NSCLC and tumor mutational burden (TMB) ≥10 mutations/megabase (high) by Foundation One CDx. The frequencies of all-cause (AC) and treatment-related (TR) adverse events (AEs) including grade 3–4 AEs were similar between the N+I and C arms, although the types of AEs differed. This study estimated the costs of managing grade 3–4 ACAEs and TRAEs in the first year after treatment initiation in CM-227 patients with high TMB. Methods: The frequency, grade, and attribution of AEs were extracted from CM-227 patient-level data. Costs of managing each grade 3–4 ACAE and grade 3–4 TRAE were estimated using related codes of the International Classification of Disease, 10th Revision, as well as cost information from the Healthcare Cost and Utilization Project National Inpatient Sample data (2015). A sensitivity analysis accounting for treatment duration and a temporal trends analysis were conducted. Results: In patients treated with N+I (n = 135), 157 grade 3–4 ACAEs and 70 grade 3–4 TRAEs were observed compared to 153 and 74 respectively among the patients treated with C (n = 159). The cost of managing grade 3–4 ACAEs per treated patient for N+I was $19,602 and for C was $16,353 (difference $3,249; 95% CI $1,774–$4,723), while the cost of managing grade 3–4 TRAEs per treated patient was $6,921 and $8,925 for N+I and C, respectively (difference $2,004; 95% CI $878–$3,131). An analysis adjusting for treatment duration yielded lower cost per person-month for N+I compared to C for both grade 3–4 ACAEs ($2,886 and $3,521; difference $634; 95% CI $379–$889) and grade 3–4 TRAEs ($1,019 and $1,921, difference $902; 95% CI $696–$1,109). For both N+I and C, the cost of managing grade 3–4 ACAEs and grade 3–4 TRAEs per person-month was highest in the first 3 months and declined thereafter. Conclusions: The cost of ACAEs was somewhat higher for N+I than for C, while the cost of TRAEs was somewhat lower for N+I than for C. Adjusting for treatment duration, N+I had lower costs for both ACAEs and TRAEs compared to C. Clinical trial information: NCT02477826.

The Adiponectin-Mortality Paradox—A Systematic Review and Meta-analysis

Surprisingly, several, though not all, studies have shown a positive relationship between serum adiponectin (ADPN) and mortality rate. In order to deeply address direction and strength of this paradoxical association, we carried out a systematic review and meta-analysis (MA) of prospective studies present in MEDLINE, Cochrane Library and Scopus by December, 1st 2017, with ADPN being the exposure and all-cause (AC) and cardiovascular (CV) mortality the outcomes. We performed random effect MA to pool individual hazard ratios (HRs; 95% CIs). To address the role of Natriuretic Peptides (NPs), known to increase both ADPN expression and mortality rate, a MA focused only on studies reporting HRs before and after NPs adjustment was also carried out. We assessed study heterogeneity by Q statistic and then performed meta-regressions considering male percentage, age, BMI, eGFR and clinical setting (general population, type 2 diabetes, CV disease, dialysis) as study level covariates. We identified 56 (n=64,775 subjects) and 30 (n=48,439) studies for AC and CV mortality, respectively. Heterogeneity across studies was observed for both outcomes (Q-test p&amp;lt;0.01). HRs, expressed as 1 SD increment of total ADPN, were 1.24 (1.17-1.30) and 1.28 (1.20-1.37) for AC and CV mortality, respectively. MA restricted to the 12 studies (n=19,010) reporting NPs data showed HRs for AC mortality equal to 1.24 (1.16-1.34) and 1.13 (1.06-1.21) without and with NPs adjustment, respectively (p&amp;lt;0.between HRs, when their correlation was &amp;gt;0.1). For CV mortality (6 studies, n=15,252), HRs were 1.21 (1.10-1.33) and 1.15 (1.06-1.24) without and with NPs adjustment, respectively (p&amp;lt;0.between HRs, when their correlation was &amp;gt;0.8). Male percentage, age, BMI, eGFR and clinical setting did not explain the observed heterogeneity among studies. Our results confirm the existence of a paradoxical association between high ADPN levels and increased mortality rate. Such paradox seems to be only partly explained by NPs levels. Disclosure M. Scarale: None. A. Fontana: None. V. Trischitta: None. M. Copetti: None. C. Menzaghi: None.

325O - Nivolumab (nivo) in combination with radiotherapy (RT) ± temozolomide (TMZ): Updated safety results from CheckMate 143 in pts with methylated or unmethylated newly diagnosed glioblastoma (GBM)

Background: Prognosis is poor for pts with GBM, as nearly all have recurrence after standard-of-care therapy. Nivo, a fully human IgG4 mAb inhibitor of the programmed death-1 receptor, is approved for the treatment of multiple cancers. Exploratory cohorts 1c and 1d of CheckMate 143 (NCT02017717) assessed the safety/tolerability of nivo in combination with RT ± TMZ in pts with newly diagnosed GBM. Methods: In cohort 1c, pts received nivo 3 mg/kg Q2W + standard RT + concurrent TMZ (75 mg/m2 daily) followed by adjuvant TMZ (150-200 mg/m2; 5 days/28-day cycle for ≥ 6 cycles). In cohort 1d, pts received nivo 3 mg/kg Q2W + standard RT without TMZ. All pts continued to receive nivo until confirmed progression/unacceptable toxicity. Pts (n = 58) were initially assigned to 1c or 1d based on MGMT methylation status (1c, methylated or unmethylated; 1d, unmethylated). Following the initial evaluation, a second group of 55 pts with unmethylated MGMT were randomized 1:1 to 1c or 1d. Pooled safety data for all 113 pts are described here. Results: Twelve pts with methylated and 43 pts with unmethylated MGMT were treated in 1c, and 58 pts with unmethylated MGMT were treated in 1d. Pts discontinued treatment in 1c (67% each arm) and 1d (83%) mostly due to radiographic progression (1c, 50% [methylated], 37% [unmethylated]; 1d, 64%), study drug toxicity (8%, 9%; 10%), or pt decision (8%, 14%; 0%). AEs (all cause) are summarized in Table. The most common (≥ 30% of pts in any arm) neurological AEs were headache (42%, 47%; 41%) and seizure (25%, 16%; 31%). No deaths due to study drug toxicity were reported.Table325O Summary of AEs (all cause)Pts, n (%)1c: Nivolumab + RT + TMZ1d: Nivolumab + RTMethylated MGMTUnmethylated MGMTUnmethylated MGMTn = 12n = 43n = 58AEs in ≥ 30% of pts in any armFatigue9 (75)22 (51)25 (43)Headache5 (42)20 (47)24 (41)Nausea6 (50)13 (30)10 (17)Seizure3 (25)7 (16)18 (31)Constipation2 (17)14 (33)4 (7)Alopecia4 (33)4 (9)7 (12)Other neurological AEs in ≥ 15% of pts in any armCognitive disorder2 (17)3 (7)6 (10)Dizziness2 (17)4 (9)5 (9)Visual field defect2 (17)2 (5)1 (2)Immune-mediated AEs in > 2 pts in any armALT increased3 (25)8 (19)7 (12)Rash1 (8)7 (16)9 (16)AST increased3 (25)7 (16)5 (9)Diarrhea06 (14)8 (14)Hypothyroidism1 (8)4 (9)6 (10)Rash maculopapular3 (25)2 (5)4 (7)Bilirubin increased1 (8)1 (2)3 (5)Creatinine increased03 (7)2 (3)Grade 3/4 AEs in > 2 pts in any armLymphocytes decreased2 (17)5 (12)2 (3)Lipase increased03 (7)4 (7)ALT increased1 (8)2 (5)3 (5)Seizure1 (8)3 (7)2 (3)Tumor flare01 (2)4 (7)Hyponatremia1 (8)03 (5)Muscular weakness01 (2)3 (5)Serious AEs in > 2 pts in any armSeizure3 (25)4 (9)7 (12)Malignant neoplasm progression2 (17)2 (5)3 (5)Pyrexia1 (8)3 (7)2 (3)Tumor flare02 (5)4 (7)Headache04 (9)1 (2) Open table in a new tab Conclusions: Nivo with RT ± TMZ was well tolerated, with the frequency of neurological AEs consistent with that in other reports in this disease. These data support continued development of nivo + RT ± TMZ in newly diagnosed GBM in the ongoing CheckMate 498 (NCT02617589) and CheckMate 548 (NCT02667587) trials. Clinical trial identification: CA209143; Revised Protocol 04d, dated September 15, 2016 Legal entity responsible for the study: Bristol-Myers Squibb Funding: Bristol-Myers Squibb Disclosure: G. Vlahovic: Ad Board: Bristol-Myers Squibb, Genentech, Merck. A. Omuro: Ad Board: Bristol-Myers Squibb, AstraZeneca, Merck, Alexion Therapeutics & Juno Therapeutics. Consulting: Stemline. D.A. Reardon: Honoraria, & Consulting: Abbvie, Amgen, Bristol-Myers Squibb, Genentech/Roche, Merck, Juno. Speakers Bureau: Genetech/Roche, Merck. Research funding: Celldex, Incyte, Inovio, Midatech. M. Lim: Honoraria & Consulting: Bristol-Myers Squibb, Merck, Agenus, Oncours. Research funding: Bristol-Myers Squibb, Agenus, Accuray. Patents/Royalty: John Hopkins. S. Sahebjam: Consulting: Bristol-Myers Squibb, Merck. Research funding: Bristol-Myers Squibb, Cortice, Merck. T. Cloughesy: Consulting: Bristol-Myers Squibb, Pfizer, Tocagen, Roche, Novocure, Nektar, VBL, Abbvie, Upshire Smith, Notable Labs, Oxigene, NewGen, Agios, Cortice, MedQia, ProNai, Wellcome, Merck, Insys, Human Longevity, Sunovion, Boston Biomedical, Alexion, Novogen. V. Potter, P. Paliwal, M. Carleton: Employee of Bristol-Myers Squibb. R. Zwirtes: Employment & stock holder with Bristol-Myers Squibb. J. Sampson: Royalties: Celldex. Shares/Equity: Istari Oncology. Consulting: Bristol-Myers Squibb. A.A. Brandes: Travel grant to ASCO by Roche. All other authors have declared no conflicts of interest.

Healthy lifestyle impact on breast cancer-specific and all-cause mortality.

While several studies have evaluated the association of combined lifestyle factors on breast cancer-specific mortality, few have included Hispanic women. We constructed a "healthy behavior index" (HBI) and evaluated its associations with mortality in non-Hispanic White (NHW) and Hispanic women diagnosed with breast cancer from the southwestern U.S. Diet and lifestyle questionnaires were analyzed for 837 women diagnosed with invasive breast cancer (1999-2004) in New Mexico as part of the 4-Corners Women's Health Study. An HBI score ranging from 0 to 12 was based on dietary pattern, physical activity, smoking, alcohol consumption, and body size and shape, with increasing scores representing less healthy characteristics. Hazard ratios for mortality over 14years of follow-up were estimated for HBI quartiles using Cox proportional hazards models adjusting for education and stratified by ethnicity and stage at diagnosis. A significant increasing trend was observed across HBI quartiles among all women, NHW women, and those diagnosed with localized or regional/distant stage of disease for all-cause (AC) mortality (p-trend=0.006, 0.002, 0.03, respectively). AC mortality was increased >2-fold for all women and NHW women in HBI Q4 versus Q1 (HR=2.18, 2.65, respectively). The association was stronger in women with regional/distant than localized stage of disease (HR=2.62, 1.94, respectively). Associations for Hispanics or breast cancer-specific mortality were not significant. These findings indicate the associations between the HBI and AC mortality, which appear to differ by ethnicity and stage at diagnosis. Interventions for breast cancer survivors should address the combination of lifestyle factors on prognosis.

Impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or without androgen deprivation therapy for unfavorable-risk prostate cancer.

68 Background: The optimal management of men with PSA failure following initial prostate cancer therapy based on comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all cause (AC), prostate cancer-specific (PCS) and other cause mortality (OCM) following PSA failure. Methods: Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT). After a median follow up of 16.2 years, 108 men experienced PSA failure (85, no or minimal; 23, moderate to severe comorbidity) and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM respectively, stratified by ACE-27 comorbidity score. Results: After a median follow up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (AHR 0.33, 95% CI 0.17-0.65, p= 0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, p= 0.0002) with a trend toward an increased risk of OCM in men with no/minimal (AHR 1.42, 95% CI 0.94-2.16, p= 0.10) and moderate/severe comorbidity (AHR 1.68, 95% CI 0.85-3.35, p= 0.14). However, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, p = 0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, p= 0.87). Conclusions: The extent and natural history of comorbidity as well as PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure. Specifically, randomized studies are needed to determine whether survival is prolonged in men with life-shortening comorbidity with salvage ADT at the time of PSA failure versus surveillance and reserving ADT use for symptomatic progression. For all other men, trials comparing ADT with or without novel agents shown to prolong survival in men with metastatic castrate resistant PC is warranted.

Impact of concomitant medication use on myocardial 123I-mIBG imaging results in patients with heart failure.

Medications that interfere with sympathetic neuronal norepinephrine uptake and storage, such as neuropsychiatrics (NP) and sympathomimetic amines, are most likely to affect cardiac uptake of iodine-123 metaiodobenzylguanidine (I-mIBG). The present study examined these and other medications reported to affect I-mIBG uptake using measurements of cardiac I-mIBG uptake on the heart failure (HF) patients in the ADMIRE-HF extension (X) study. Baseline concomitant medications taken by the 961 HF patients were categorized into five groups: calcium channel blockers, NP medications, β agonists and sympathomimetics, α antagonists, and other antihypertensives. NP medications were further subcategorized into those expected to have high and low impact on norepinephrine transporter (NET) function. Myocardial I-mIBG heart/mediastinum (H/M) uptake ratios on 4 h planar images were compared among the groups. Impact of medication group on the prognostic value of the H/M ratio for all-cause (AC) and cardiac death during a median 2-year follow-up was also examined. A total of 283 (29%) patients were using at least one calcium channel blocker, NP medication, or β agonist or sympathomimetic. These patients had a lower mean H/M ratio than the other study patients (1.42±0.20 vs. 1.45±0.20; P=0.022). However, the 2-year AC mortality rates in the two groups were the same [11.3% (95% confidence interval: 7.5-15.2%) vs. 11.8% (95% confidence interval: 9.2-14.4%)]. In terms of medication categories, there were no significant differences in the mean H/M ratios between patients who did and did not use NP medications, β agonists, calcium channel blockers, and α antagonists. Across all categories, patients with H/M ratio greater than or equal to 1.60 had lower AC and cardiac mortality. Patients using higher potency (for NET inhibition) NP medications had significantly lower H/M ratio values, but the prognostic significance of H/M ratio greater than or equal to 1.60 was unchanged. Only a small number of higher potency NET-inhibiting NP medications have a measurable effect on the results of I-mIBG myocardial imaging. There appears to be no basis for restricting the use of calcium channel blockers and β agonist respiratory medications in HF patients referred for cardiac I-mIBG imaging.

Children's Hospital Characteristics and Readmission Metrics.

Like their adult counterparts, pediatric hospitals are increasingly at risk for financial penalties based on readmissions. Limited information is available on how the composition of a hospital's patient population affects performance on this metric and hence affects reimbursement for hospitals providing pediatric care. We sought to determine whether applying different readmission metrics differentially affects hospital performance based on the characteristics of patients a hospital serves. We performed a cross-sectional analysis of 64 children's hospitals from the Children's Hospital Association Case Mix Comparative Database 2012 and 2013. We calculated 30-day observed-to-expected readmission ratios by using both all-cause (AC) and Potentially Preventable Readmissions (PPR) metrics. We examined the association between observed-to-expected rates and hospital characteristics by using multivariable linear regression. We examined a total of 1 416 716 hospitalizations. The mean AC 30-day readmission rate was 11.3% (range 4.3%-19.6%); the mean PPR rate was 4.9% (range 2.9%-6.9%). The average 30-day AC observed-to-expected ratio was 0.96 (range 0.63-1.23), compared with 0.95 (range 0.65-1.23) for PPR; 59% of hospitals performed better than expected on both measures. Hospitals with higher volumes, lower percentages of infants, and higher percentage of patients with low income performed worse than expected on PPR. High-volume hospitals, those that serve fewer infants, and those with a high percentage of patients from low-income neighborhoods have higher than expected PPR rates and are at higher risk of reimbursement penalties.

Safety and Efficacy of Carfilzomib (CFZ) in Previously-Treated Systemic Light-Chain (AL) Amyloidosis

Safety and Efficacy of Carfilzomib (CFZ) in Previously-Treated Systemic Light-Chain (AL) Amyloidosis

Safety and efficacy of carfilzomib (CFZ) in previously-treated systemic light-chain (AL) amyloidosis

Safety and efficacy of carfilzomib (CFZ) in previously-treated systemic light-chain (AL) amyloidosis

Abstract LB-190: Ethnic differences in the relationship between diabetes, adiposity measures and breast cancer-specific mortality

Abstract Background: Type 2 diabetes and obesity are modifiable factors that are associated with breast cancer (BC) specific and all-cause (AC) mortality among women with BC. Few studies have examined the role of adiposity in the association between diabetes and BC outcomes, particularly among Hispanic women who have high prevalence of obesity and diabetes. We hypothesized that adiposity mediates the association between diabetes and risk of BC-specific and AC mortality in BC survivors from the Breast Cancer Health Disparities Study. Methods: The study population included 2,478 women (1,180 Hispanics, 1,298 non-Hispanic whites (NHW)) from the San Francisco Bay Area, New Mexico, Utah, Colorado and Arizona with incident, invasive breast cancer diagnosed between April 1995 and April 2002 or between October 1999 and May 2004, depending on study site. Information on diabetes and lifestyle factors was collected by in-person interview, as well as self-reported weight and height during the referent year, and measured waist and hip circumferences. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards regression models for overall associations and by ethnicity. Covariates of interests included ethnicity, age at diagnosis, breast cancer stage, tumor phenotype, study site, education, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), diet, physical activity, smoking and alcohol use. Results: The median follow-up time was 10.8 years since BC diagnosis, with a total of 466 deaths from any cause. Overall, in multivariable models physician diagnosis of diabetes was significantly associated with BC-specific (HR, 1.69; 95% CI 1.14-2.51) and AC mortality (HR, 1.62; 95% CI 1.22-2.19). The association was stronger among Hispanic women for BC-specific mortality (HR, 1.83; 95% CI 1.11-3.03) compared to NHWs (HR, 1.53; 95% CI 0.79-2.95). Further adjustment for BMI, WC and WHR attenuated the point estimates for AC and BC-specific mortality, and the degree of attenuation varied by ethnicity and adiposity measure. For example, WHR was the only measure that significantly attenuated the point estimate among Hispanic women for BC-specific mortality (by 15%). Weight gain between age 30 and referent year was also evaluated; diabetics who gained 25 kg or more had a significant increase in BC-specific mortality (HR, 5.04; 95% CI 1.69-15.07) compared to non-diabetic women. Lastly, BC-specific mortality was significant among women diagnosed with diabetes within five years of BC diagnosis (HR, 2.33, 95% CI 1.31-4.13), compared to non-diabetic women. Conclusions: Diabetes was associated with BC-specific mortality, particularly among Hispanic women and abdominal adiposity based on WHR was a significant mediator of this association. Future studies of diabetes and BC outcomes among diverse populations should examine changes in WHR among Hispanic BC survivors. Citation Format: Avonne E. Connor, Kala Visvanathan, Kathy Baumgartner, Richard N. Baumgartner, Stephanie Boone, Lisa M. Hines, Anna R. Giuliano, Esther M. John, Roger K. Wolff, Martha L. Slattery. Ethnic differences in the relationship between diabetes, adiposity measures and breast cancer-specific mortality. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-190. doi:10.1158/1538-7445.AM2015-LB-190