Search

Background Real-world evidence suggest that next generation hormonal agents (NHAs) abiraterone and enzalutamide were preferred as first-line (1L) therapies for metastatic castration-resistant prostate cancer (mCRPC) in the United States (US) pre-2020, with chemotherapies, particularly docetaxel, being preferred in subsequent lines (2L+). This real-world study described patient characteristics, treatment patterns, time on treatment (ToT) and overall survival (OS) among patients with mCRPC treated with 2L and 3L docetaxel post-NHAs in the mCRPC setting. Methods Adults with confirmed adenocarcinoma mCRPC diagnosis and ≥1 month of follow-up post-diagnosis were selected from a US electronic health record-derived oncology de-identified database (01/2013–03/2019). Based on the observed line of therapy sequences post-mCRPC diagnosis, patients who received NHA therapy in 1L and docetaxel therapy in 2L were included in the 2L docetaxel cohort, and patients who received NHA therapy in both 1L and 2L and docetaxel therapy in 3L were included in the 3L docetaxel cohort. ToT and OS were evaluated using Kaplan-Meier analysis. Results Among 5,213 patients with mCRPC, 278 and 166 were included in the 2L and the 3L docetaxel cohorts, respectively (median age: 73 years for both cohorts). ADT was the most used class of medication pre-mCRPC (>75%). For the 2L cohort, the most common sequence post-mCRPC was 1L abiraterone → 2L docetaxel (52.5%), while the median ToT and OS post-2L start were 4.1 and 10.5 months, respectively; for the 3L cohort, the most common sequence post-mCRPC was 1L abiraterone → 2L enzalutamide → 3L docetaxel (67.5%), while the median ToT and OS post-3L start were 3.8 and 8.7 months, respectively. Conclusions This real-world study provides novel data on patients treated with docetaxel post-NHAs in a mCRPC setting and highlights the critical unmet need for developing more effective treatment options in this population.

Background: Progression trajectories of patients with mild cognitive impairment (MCI) are currently not well understood. Objective: To classify patients with incident MCI into different latent classes of progression and identify predictors of progression class. Methods: Participants with incident MCI were identified from the US National Alzheimer’s Coordinating Center Uniform Data Set (09/2005-02/2019). Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and Mini-Mental State Examination (MMSE) score longitudinal trajectories from MCI diagnosis were fitted using growth mixture models. Predictors of progression class were identified using multivariate multinomial logistic regression models; odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Results: In total, 21%, 22%, and 57% of participants (N = 830) experienced fast, slow, and no progression on CDR-SB, respectively; for FAQ, these figures were 14%, 23%, and 64%, respectively. CDR-SB and FAQ class membership was concordant for most participants (77%). Older age (≥86 versus≤70 years, OR [95% CI] = 5.26 [1.78–15.54]), one copy of APOE ɛ4 (1.94 [1.08–3.47]), higher baseline CDR-SB (2.46 [1.56–3.88]), lower baseline MMSE (0.85 [0.75–0.97]), and higher baseline FAQ (1.13 [1.02–1.26]) scores were significant predictors of fast progression versus no progression based on CDR-SB (all p

Aim: To assess the patterns of genetic testing for homologous recombination repair mutations in patients with metastatic castration-resistant prostate cancer (mCRPC) pre-PARP inhibitors approval. Patients & methods: mCRPC patients were selected in an oncology electronic medical records database. Patterns and predictors of testing for ATM, BRCA1/2, CDK12, PALB2 and FANCA gene alterations were assessed. Results: Of 5213 mCRPC patients, 674 (13%) had a documented genetic test. The number of tested patients increased from 1 in 2013 to 313 in 2018 (out of 3161 and 3010 clinically active patients, respectively). Receiving care in an academic oncology center (versus a community-based center) strongly predicted genetic testing (hazard ratio = 2.41). Conclusion: The use of and access to genetic testing pre-PARP inhibitor approval was suboptimal.

Introduction Therapeutic options for metastatic castration-resistant prostate cancer (mCRPC) patients are continuously advancing. We described mCRPC treatment patterns in the US from 2013 to 2019. Methods Patients with a confirmed mCRPC diagnosis and adenocarcinoma histology were included in the US Flatiron Health Electronic Health Record-derived de-identified database. Treatment patterns [including treatment per lines of therapies (LOTs), LOT sequences, and time on treatment] and overall survival (OS) have been described in mCRPC settings. Results Of 5213 patients (mean age: 72.6 years), 4374 (83.9%) were treated with ≥ 1 LOT post-mCRPC diagnosis (among those with ≥ 1 LOT, 55.3%, 29.5%, 14.7%, and 6.7% had ≥ 2, 3, 4, and 5 LOTs, respectively). In first line (1L), the main treatment class was next-generation hormonal agents (NHA; 62.5% of patients with ≥ 1 LOT), while the shortest and longest time on 1L were observed for chemotherapy (median 2.8 months) and NHA (median 5.1 months), respectively. The most common LOT sequences were NHA → NHA (29.4% of patients with ≥ 2 LOTs) and NHA → NHA → chemotherapy (16.7% of patients with ≥ 3 LOTs). In Kaplan–Meier analyses, the median OS was 19.4, 14.6, and 11.1 months post-1L, 2L, and 3L start, respectively. Patients who moved rapidly through LOTs had an increased risk of death. Conclusions NHA were widely used as 1L therapy in mCRPC patients from 2013 to 2019, but time on 1L NHA treatment was on average

Introduction This study described patients hospitalized for acute heart failure (AHF) in Japan who received intravenous (IV) diuretics and/or vasodilators as the initial therapy. Methods The Japan Medical Data Vision database was used to identify adult patients hospitalized for AHF during 2013–2017, who were hemodynamically stable at presentation and treated with IV diuretics and/or IV vasodilators as initial therapy. Treatment patterns and use of cardiac rehabilitation, as well as outcomes (e.g., length of stay [LOS], in-hospital mortality, HF-readmission) were reported overall and by year of AHF hospitalization. Results Of 30,360 patients (mean age = 80.0 years; 52.2% male), 87.0% were treated during the hospitalization with IV diuretics, 63.9% with IV vasodilators, and 13.8% with intensified therapies. On average, the duration of IV therapy was 10.6 days. In-hospital cardiac rehabilitation was utilized by 51.7% of the patients for 11.7 days on average. Mean LOS was 23.3 days, while in-hospital mortality and 30-day HF readmission post-discharge were 13.2 and 9.5%, respectively. Hospitalization outcomes remained stable between 2013 and 2017 despite important changes in AHF management such as a decrease in carperitide use (55.9–40.0% in 2017), and increases in use of tolvaptan (from 14.2% in 2013 to 31.3% in 2017) and of cardiac rehabilitation (from 43.2% in 2013 to 56.1% in 2017). Patients with intensified therapies had the longest IV therapy duration (mean 23.8 days vs. 5.5–9.9 days), the highest cardiac rehabilitation services use (60.2 vs. 38.3–57.0%), the longest LOS (mean 36.7 vs. 16.3–22.2 days), and the highest in-hospital mortality (37.4 vs. 3.1–12.4%) compared to the other treatment groups. Conclusions Contemporary treatment for AHF hospitalization in Japan comprises a long duration of IV therapy followed by extended use of oral medications and in-hospital cardiac rehabilitation prior to discharge. Patients requiring intensified therapies had much longer LOS and higher in-hospital mortality. Supplementary Information The online version contains supplementary material available at 10.1007/s40119-021-00212-y.

Objectives This study sought to characterize in-hospital treatment patterns and associated patient outcomes among patients hospitalized for heart failure (HF) in U.S. clinical practice. Background Hospitalizations for HF are common and associated with poor patient outcomes. Real-world patterns of in-hospital treatment, including diuretic therapy, in contemporary U.S. practice are unknown. Methods Using Optum de-identified Electronic Health Record data from 2007 through 2018, patients hospitalized for a primary diagnosis of HF (ejection fraction ≤40%) and who were hemodynamically stable at admission, without concurrent acute coronary syndrome or end-stage renal disease, and treated with intravenous (IV) diuretic agents within 48 h of admission were identified. Patients were categorized into 1 of 4 mutually exclusive hierarchical treatment groups defined by complexity of treatment during hospitalization (intensified treatment with mechanical support or IV vasoactive therapy, IV diuretic therapy reinitiated after discontinuation for ≥1 day without intensified treatment, IV diuretic dose increase/combination diuretic treatment without intensified treatment or IV diuretic reinitiation, or uncomplicated). Results Of 22,677 patients hospitalized for HF with reduced ejection fraction (HFrEF), 66% had uncomplicated hospitalizations without escalation of treatment beyond initial IV diuretic therapy. Among 7,809 remaining patients, the highest level of therapy received was IV diuretic dose increase/combination diuretic treatment in 25%, IV diuretic reinitiation in 36%, and intensified therapy in 39%. Overall, 19% of all patients had reinitiation of IV diuretic agents (26% of such patients had multiple instances), 12% were simultaneously treated with multiple diuretics, and 61% were transitioned to oral diuretic agents before discharge. Compared with uncomplicated treatment, IV diuretic reinitiation and intensified treatment were associated with significantly longer median length of stay (uncomplicated: 4 days; IV diuretic reinitiation: 8 days; intensified: 10 days) and higher rates of in-hospital (uncomplicated: 1.6%; IV diuretic reinitiation: 4.2%; intensified: 13.2%) and 30-day post-discharge mortality (uncomplicated: 5.2%; IV diuretic reinitiation: 9.7%; intensified: 12.7%). Conclusions In this contemporary real-world population of U.S. patients hospitalized for HFrEF, one-third of patients had in-hospital treatment escalated beyond initial IV diuretic therapy. These more complex treatment patterns were associated with highly variable patterns of diuretic use, longer hospital lengths of stay, and higher mortality. Standardized and evidence-based approaches are needed to improve the efficiency and effectiveness of in-hospital HFrEF care.

Introduction Patients with chronic hepatitis C virus infection (HCV) may incur significant indirect costs due to health-related work loss. However, the impact of curative HCV therapy on work productivity is not well characterized. We estimated the economic value of improved productivity following HCV treatment. Methods Adults diagnosed with HCV infection (Optum Healthcare Solutions data; Q1 1999 to Q1 2017) were stratified into two cohorts: (1) treated cohort, patients who received HCV therapy and (2) untreated cohort, therapy-naïve patients. For the treated cohort, the index date was set at the end of the post-treatment monitoring period, assumed to be 6 months after the end of treatment for patients with cirrhosis or for those treated with interferon-based therapy, and 3 months after the end of treatment for patients without cirrhosis who received interferon-free therapy. For the untreated cohort, an index date was randomly selected post-HCV diagnosis. Time from the index date to the first work-loss event was assessed using time to event analyses. An economic modeling approach was used to monetize the improved productivity from reduced risk of work-loss event in the 4 years post-index. Results Patients in the treated cohort had a lower risk of experiencing a work-loss event compared to untreated patients [unadjusted and adjusted hazard ratios and 95% CI 0.72 (0.61–0.86), and 0.68 (0.55–0.85), respectively; p

Due to limited treatment options, many patients with diabetic gastroparesis (DG) or idiopathic gastroparesis (IG) experience inadequate symptom control resulting in increased health-care resource utilization (HRU) and associated costs. We compared all-cause HRU and health-care costs over the 3 years after patients' first gastroparesis diagnosis with that of matched controls without gastroparesis.Newly diagnosed adults with DG or IG were identified in Optum's de-identified ClinformaticsDemographics and comorbidities were balanced between patients with gastroparesis (n = 18,015 [DG]; n = 14,305 [IG]) and controls. In each of the Years 1-3 post-index, patients with DG or IG had significantly higher annual HRU and costs versus controls (mean total cost differences PPY: DG Year 1 $34,885, Year 2 $28,071, Year 3 $25,606; IG Year 1 $23,176, Year 2 $16,627, Year 3 $14,396) (all p 0.05). Across all 3 years, DG/IG cohorts had approximately twice the costs of controls. HRU and costs were highest in Year 1 post-index for both DG and IG.The economic burden of gastroparesis remains high several years after diagnosis, emphasizing the need for chronic treatment to effectively manage symptoms and consequently reduce the burden of this disorder.

Objective To estimate health‐related quality of life (HRQoL) in patients with tuberous sclerosis complex (TSC) and associated manifestations and to identify potential factors associated with HRQoL in this population of patients. Methods We performed a retrospective chart review of adults with TSC who attended the outpatient clinic of the University Medical Center Utrecht in the Netherlands from 1990 to 2015 (N = 363; on average 33.6 years of follow‐up). HRQoL data were assessed in 2012 using the Health Utility Index version 3 (HUI‐3) questionnaire completed by patients or caregivers (N = 214 with HUI score and ≥1 TSC manifestation, including renal angiomyolipomas [rAMLs], subependymal giant cell astrocytoma [SEGA], or epilepsy). Results Of 214 patients in the study sample, 171 had TSC‐associated epilepsy (with or without rAML/SEGA), 37 had TSC and rAML (without epilepsy or SEGA), and 6 had other combinations of manifestations. The median HUI score for the 214 patients with ≥1 TSC manifestation was 0.51 (−0.371 to 1 scale, 1 = perfect health, 0 = death

The aim of this study was to understand the reasons for canakinumab initiation among patients with Still's disease, including systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still's disease (AOSD), in US clinical practice.Physicians retrospectively reviewed the medical charts of patients with Still's disease (regardless of age at symptom onset) who were prescribed canakinumab from 2016 to 2018. Patients aged16 years at symptom onset were classified as having SJIA and those aged ≥ 16 years at symptom onset (calculated from case-record forms) were classified as having AOSD. Patient treatment history and physician reasons for canakinumab initiation were analyzed. Overall results were presented as SJIA/AOSD. Sensitivity analyses were performed for the robustness of the results.Forty-three physicians in the USA (rheumatologists/dermatologists/immunologists/allergists: 51.2/27.9/11.6/9.3%; subspecialty in adults/pediatrics: 67.4/32.6%) abstracted information for 72 patients with SJIA/AOSD (SJIA/AOSD/age unknown at symptom onset: 75.0/18.1/6.9%; mean age 19.4 years; children 61.1%; females 56.9%). Most patients (90.3%) received treatment directly preceding canakinumab initiation (etanercept 27.7%; anakinra 18.5%; adalimumab 16.9%); the respective treatment was discontinued due to lack of efficacy/effectiveness (43.1%) and availability of a new treatment (27.8%). Most common reasons for canakinumab initiation were physician perceived/experienced efficacy/effectiveness of canakinumab (77.8%; children/adults: 81.8/71.4%), lack-of-response to previous treatment (45.8%; children/adults: 36.4/60.7%), convenient administration/dosing (26.4%; children/adults: 29.5/21.4%) and ability to discontinue/spare steroids (25.0%; children/adults: 20.5/32.1%). The sensitivity analysis provided similar results.In US clinical practice, physician perceived/experienced efficacy/effectiveness of canakinumab and lack-of-response to previous treatment were the primary reasons for canakinumab initiation among patients with SJIA/AOSD. Physician perceived/experienced efficacy/effectiveness and convenient administration/dosing of canakinumab were the most common reasons for canakinumab initiation among children, whereas lack-of-response to previous treatment and ability to discontinue/spare steroids being the most frequent reasons among adults.

Background Although canakinumab has demonstrated efficacy in multiple trials in patients with periodic fever syndromes (PFS), the evidence on initiation of canakinumab among PFS patients in real world setting is not well understood. We aimed to characterize the reasons for canakinumab initiation among patients with PFS, specifically, cryopyrin-associated periodic syndrome (CAPS), hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF). Methods Physicians retrospectively reviewed the medical charts of PFS patients prescribed canakinumab between 2016 and 2018. Information collected included patient clinical characteristics, reasons for previous treatment discontinuation and canakinumab initiation. The results were summarized for overall patients, and by children ( Results Fifty-eight physicians in the US (rheumatologists, 44.8 %; allergists/immunologists, 29.3 %; dermatologists, 25.9 %) abstracted information for 147 patients (children, 46.3 %; males, 57.1 %; CAPS, 36.7 %; TRAPS, 26.5 %; FMF, 26.5 %; HIDS/MKD, 6.8 %; Mixed, 3.4 %). Overall, most patients (90.5 %) received treatment directly preceding canakinumab (NSAIDs, 27.8 % [40.0 % in HIDS/MKD]; anakinra, 24.1 % [32.7 % in CAPS]; colchicine, 21.8 % [35.9 % in FMF]), which were discontinued due to lack of efficacy/effectiveness (39.5 %) and availability of a new treatment (36.1 %). The common reasons for canakinumab initiation were physician perceived efficacy/effectiveness (81.0 %; children, 75.0 %; adults, 86.1 %), lack of response to previous treatment (40.8 %; children, 38.2 %; adults, 43.0 %) and favorable safety profile/tolerability (40.1 %; children, 42.6 %; adults, 38.0 %). Within subtypes, efficacy/effectiveness was the most stated reason for canakinumab initiation in HIDS/MKD (90.9 %), lack of response to previous treatment in FMF (52.4 %) and convenience of administration/dosing in CAPS (27.1 %). Conclusions This study provided insights into how canakinumab is initiated in US clinical practice among PFS patients, with physician perceived efficacy/effectiveness of canakinumab, lack of response to previous treatment and favorable safety profile/tolerability of canakinumab being the dominant reasons for canakinumab initiation in all patients and in children and adults and PFS subtypes. Notably, the favorable safety profile/tolerability of canakinumab was more often the reason for initiation among children versus adults.

Aim: To estimate incidence of stage III melanoma using the American Joint Committee on Cancer (AJCC) staging, 7th and 8th edition. Patients & methods: The SEER US cancer registry was analyzed (2010–2014). AJCC7 stages were recorded in the data; AJCC8 stages were inferred. Results: Of 106,195 melanoma patients, 7669 and 7342 had stage III melanoma by AJCC7 and AJCC8, respectively (95% overlap). Nearly 30% of patients with AJCC7 stage III melanoma were reclassified in a higher stage III group by AJCC8 versus 7% in lower stage group. Regardless of the AJCC edition, incidence of stage III melanoma has increased from 2010 to 2014 both overall and within each stage III group. Conclusion: Providing appropriate management to this growing population of high-risk patients is a priority.

Supplemental Digital Content is available in the text., Surgery is the mainstay treatment for operable nonmetastatic melanoma, but recurrences are common and limit patients’ survival. This study aimed to describe real-world patterns of treatment and recurrence in patients with melanoma and to quantify healthcare resource utilization (HRU) and costs associated with episodes of locoregional/distant recurrences. Adults with nonmetastatic melanoma who underwent melanoma lymph node surgery were identified from the Truven Health MarketScan database (1 January 2008 to 31 July 2017). Locoregional and distant recurrence(s) were identified on the basis of postsurgery recurrence indicators (i.e. initiation of new melanoma pharmacotherapy, new radiotherapy, or new surgery; secondary malignancy diagnoses). Of 6400 eligible patients, 219 (3.4%) initiated adjuvant therapy within 3 months of surgery, mostly with interferon α-2b (n=206/219, 94.1%). A total of 1191/6400 (18.6%) patients developed recurrence(s) over a median follow-up of 23.1 months (102/6400, 1.6% distant recurrences). Among the 219 patients initiated on adjuvant therapy, 73 (33.3%) experienced recurrences (distant recurrences: 13/219, 5.9%). The mean total all-cause healthcare cost was $2645 per patient per month (PPPM) during locoregional recurrence episodes and $12 940 PPPM during distant recurrence episodes. In the year after recurrence, HRU was particularly higher in patients with distant recurrence versus recurrence-free matched controls: by 9.2 inpatient admissions, 54.4 inpatient days, 8.8 emergency department admissions, and 185.9 outpatient visits (per 100 person-months), whereas all-cause healthcare costs were higher by $14 953 PPPM. It remains to be determined whether the new generation of adjuvant therapies, such as immune checkpoint inhibitors and targeted agents, will increase the use of adjuvant therapies, and reduce the risk of recurrences and associated HRU/cost.

OBJECTIVE To assess the economic burden of tenosynovial giant cell tumor (TGCT) among US employed workforce. METHODS Patients with TGCT medical claims (N = 1395) and matched controls (1:10) without TGCT claims (N = 13,950) were identified from the OptumHealth Care Solutions, Inc. database (January 1, 1999 to March 31, 2017). Adjusted regression models were used to compare healthcare resource utilization, time lost from work, and associated costs between cohorts. RESULTS In patients with TGCT, the rates of inpatient admissions, emergency room visits, outpatient visits, and work loss days were 2.8, 1.5, 2.2, and 2.6 times those of matched controls, respectively (all P

This study compared progression, progression-free survival (PFS), overall survival (OS), and treatment changes among chronic myelogenous leukemia patients in chronic phase (CML-CP) receiving nilotinib or dasatinib as second-line therapy. Information on CML-CP patients switched from imatinib to nilotinib or dasatinib as second-line therapy was collected retrospectively from 122 US hematologists and oncologists through an online medical chart review. Progression, PFS, and OS were compared using multivariate Cox proportional hazard models, and treatment changes using chi-square tests. Of 597 imatinib resistant or intolerant patients, 301 initiated nilotinib and 296 dasatinib as second-line therapy. Nilotinib was associated with a lower risk of progression (hazard ratio [HR] = 0.27; p = 0.021) and longer PFS (HR = 0.48; p = 0.030) than dasatinib, with a median follow-up time of 11 months for nilotinib and 10 months for dasatinib. Nilotinib patients had a lower estimated hazard of mortality than dasatinib patients, though not statistically significant (HR = 0.46; p = 0.067). When treatment changes were classified by the physicians’ justifications, fewer nilotinib patients had treatment changes due to ineffectiveness (2.0% vs. 5.1%, p = 0.041) or drug holidays due to intolerance (0.0% vs. 1.7%, p = 0.024) than dasatinib patients. Among CML-CP patients in this retrospective chart review who switched from imatinib to either nilotinib or dasatinib, nilotinib was associated with a significantly lower risk of progression and longer PFS than dasatinib. Nilotinib patients were also less likely than dasatinib patients to subsequently have treatment changes due to ineffectiveness or drug holidays due to intolerance. These findings could be subject to unobserved confounders.

Background To compare the risk of severe hepatotoxicity with anidulafungin versus caspofungin and micafungin in hospitalized adults. Methods This retrospective cohort study combined data from two large US- based hospital electronic medical record databases. Severe hepatotoxicity was a Grade ≥ 3 liver function test (LFT) post-echinocandin initiation. Adjusted incidence rate ratios (IRRs) were estimated for anidulafungin versus caspofungin and micafungin, overall and in patients with normal baseline LFT (Grade 0). Results Treatments included anidulafungin (n = 1700), caspofungin (n = 4431), or micafungin (n = 6547). The proportions with LFT Grade ≥ 3 pre-echinocandin initiation were: anidulafungin 40.4% versus caspofungin 25.9% (p

Objectives Elderly patients with advanced non-small lung cancer (aNSCLC) represent a high-risk patient population due to disease burden, comorbidities, and performance status, particularly after progressing on first-line therapy. Among elderly patients who receive second-line therapy, treatment related toxicities can have substantial impact on both clinical and economic outcomes. This study assessed the impact of severe adverse events (AEs) during second-line therapy on overall survival (OS) and all-cause heathcare costs in elderly with aNSCLC. Materials and methods Patients with aNSCLC aged ≥65 years who initiated second-line chemotherapy/targeted therapy were identified in the SEER-Medicare database (2007–2011). Fifty-seven AEs were identified by literature review and consultation with two oncologists. Severe AEs were defined as AEs that required a hospitalization and were operationalized based on AE diagnosis(es) recorded during hospitalizations. OS post-second-line initiation and healthcare costs during second-line were compared between patients with and without severe AEs. Results Among 3967 patients initiating second-line therapy, 1624 (41%) had ≥1 severe AE, where hypertension (26%), anemia (24%), and pneumonia (23%) were most commonly reported. Patients with and without severe AEs had similar demographic and cancer characteristics at diagnosis and similar second-line treatment regimens, but patients with severe AEs had more comorbidities at second-line initiation. Median OS was lower in patients with versus without severe AEs (6 vs. 11 months). After multivariate adjustment, hazard of death was more than twice higher in patients with versus without severe AEs (adjusted hazard ratio [HR] 2.31, 95% CI 2.16–2.47). Healthcare costs were more than twice higher in patients with versus without severe AEs ($16,135 vs. $7559 per-patient-per-month). Conclusion Severe AEs among elderly patients with aNSCLC treated with second-line chemotherapy/targeted therapy were found to be associated with decreased OS and increased healthcare costs. Results suggest a potential link between severe AEs in second-line treated aNSCLC elderly and patient survival and economic burden to the healthcare system.

Purpose To describe the patient characteristics, treatments, disease monitoring, and kidney function of patients with sporadic angiomyolipoma (sAML), stratified by the number and size of renal angiomyolipomas (AMLs). Methods Single-center retrospective analysis of patients with sAML treated from 1990 to 2015 in a dedicated clinic for inheritable tumor syndromes in a tertiary referral center from the Netherlands. Patients’ first AML assessment at the clinic was defined as the index date. Patient characteristics were measured at the index date. Treatments, disease monitoring, and kidney function were measured post-index date. Results The study sample included 53 patients followed for a total of 184.6 patient-years. At the index date, the largest AML was ≥ 3.5 cm for 26 patients and

Aim: Despite long-term responses to first-line immunochemotherapy, many patients with diffuse large B-cell lymphoma (DLBCL) have relapsed/refractory disease. Second-line treatment options are available. However, a large proportion of patients are ineligible for transplantation/intensive therapy. Patients & methods: This observational study of 702 patients in the USA, who used second-line therapies for relapsed/refractory DLBCL, evaluated treatment patterns and overall survival (OS). The study focused on the OS outcome of patients receiving second-line rituximab–bendamustine or rituximab–gemcitabine–oxaliplatin. Results & conclusion: Rituximab–bendamustine and rituximab–gemcitabine–oxaliplatin were received by 4.6 and 1.4% of patients, respectively (N = 42/702). Median and 1-year OS rates were similar between regimens. Many of the 200 different treatment regimens observed in second line were modified versions of National Comprehensive Cancer Network regimens.

BACKGROUND The number of women with congenital heart disease (CHD) of reproductive age is increasing, yet a description of trends in pregnancy and delivery outcomes in this population is lacking. OBJECTIVE To assess secular trends in pregnancy rates, delivery outcomes, and related health care utilization in the adult female CHD population in Quebec, Canada. METHODS The Quebec CHD database was used to construct a cohort with all women with CHD aged 18-45 years between 1992 and 2004. Pregnancy and delivery rates were determined yearly and compared to the general population. Secular trends in pregnancy and delivery rates were assessed with linear regression. The cesarean delivery rate in the CHD population was compared to the general population. Predictors of cesarean section were determined with multivariable logistic regression. Cox regression, adjusted for comorbidities, was used to analyze the impact of cesarean sections on 1-year health care use following delivery. RESULTS About 14 878 women were included. A total of 10 809 pregnancies were identified in 5641 women, of whom 4551 (80%) and 2528 (45%) experienced at least one delivery and/or abortion, respectively. Absolute yearly numbers and rates of pregnancies and deliveries increased during the study period (P

e18746 Background: Limited real-world data exists on the treatment of HER2+ metastatic breast cancer (mBC) following pertuzumab (P)+trastuzumab (T) based regimens in first-line (1L) setting. In the EMILIA trial, T-DM1 had higher median progression-free survival (mPFS) (9.6 months vs. 6.4 months) and median overall survival (mOS) (30.9 months vs. 25.1 months) than lapatinib plus capecitabine in patients previously treated with trastuzumab and a taxane. Real-world treatment effectiveness data following 1L P+T could complement clinical trial data to help inform understanding of unmet needs of HER2+ mBC patients requiring second-line (2L) treatment. Methods: IQVIA Oncology EMR (US) database was analyzed to identify adult patients with confirmed HER2+ mBC who were treated with a 1L P+T based regimen between Jan 2015-Sep 2019. An anti-HER2-based regimen might include hormonal therapy and/or chemotherapy. Eligible patients who had ≥60 days of follow-up since 1L P+T regimen initiation were included in outcomes assessment. Treatment discontinuation was defined as a treatment gap of at least 365 days, initiation of a new line of therapy, or death. Treatment failure was defined as the initiation of a new line of therapy or death. A new line of therapy was defined as the use of another anti-HER2 agent, switching to a different class of chemotherapy, or re-initiation of the same regimen after a gap of at least 365 days. Median duration of anti-HER2 regimen, median time to treatment failure (mTTF) and median overall survival (mOS) were estimated using Kaplan-Meier analysis. Results: A total of 710 patients were treated with a 1L P+T based regimen (median age: 57 years; 47% HR+, 26% HR- and 27% unknown HR status; 80% received a taxane). Median follow-up was 20.3 months. Median treatment duration for 1L P+T regimens was 15.3 months. A total of 302 patients (43%) discontinued 1L P+T treatment during the study, of which 222 patients received 2L therapy with a median follow-up of 9.6 months post 2L initiation. Among patients receiving 2L treatment, 214 (96%) received anti-HER2-based regimens. T-DM1 based regimens were most common (n = 159; 72%), followed by trastuzumab-based regimens (n = 29; 13%), lapatinib-based regimens (n = 13; 6%) and neratinib (n = 13; 6%). Overall, median 2L treatment duration was 5.9 months, mTTF was 8.6 months, and mOS was 25.4 months. For patients receiving T-DM1 as 2L therapy, median duration of T-DM1 treatment was 5.7 months, mTTF was 7.9 months, and mOS was 24.4 months. Conclusions: T-DM1 was the most common 2L treatment following 1L P+T based regimen for HER2+ mBC. Median TTF and mOS for T-DM1 in this study were numerically shorter than mPFS and mOS reported in the EMILIA trial, possibly due to the inclusion of a broader patient population beyond those studied in a clinical trial in the current study. There remains an unmet need of a more effective treatment for HER2+ mBC after 1L treatment.

Background— The burden of low-dose ionizing radiation (LDIR) exposure from medical procedures among individuals with congenital heart disease (CHD) is unknown. In this longitudinal population-based study, we sought to determine exposure to LDIR-related cardiac imaging and therapeutic procedures in children and adults with CHD. Methods and Results— In an analysis of the Quebec CHD database, exposure to the following LDIR-related cardiac procedures was recorded: catheter-based diagnostic procedures, structural heart interventions, coronary interventions, computed tomography scans of the chest, nuclear procedures, and pacemaker/implantable cardioverter-defibrillator insertion and repair. From 1990 to 2005, there were 16 253 LDIR-exposed patients with CHD with 317 988 patient-years of available follow-up. The total number of LDIR-related procedures increased from 18.5 to 51.9 per 1000 CHD patients per year ( P Conclusions— From 1990 to 2005, patients with CHD were exposed to increasing numbers of LDIR-emitting cardiac procedures. This exposure occurred at progressively younger ages. These findings provide an important perspective on longitudinal LDIR exposure in this at-risk population.

Supplemental Digital Content is available in the text., Patients with BRAF V600 (BRAF) mutated metastatic melanoma are eligible for therapy with both immune checkpoint inhibitors and targeted therapies, making treatment choice a complex decision. The present study aimed to describe patterns of treatment with immunotherapy and targeted therapy and BRAF testing in patients with metastatic melanoma presumed to have BRAF mutations (BRAF+) in the years following the approval of the newer generation of immune checkpoint inhibitors and targeted therapies (2014–2016). Two large US commercial claims databases [Truven Health Analytics MarketScan and IQVIA Real-World Data Adjudicated Claims – USA (IQVIA RWD Adjudicated Claims – USA)] were used. Patients were presumed BRAF+ if they received at least 2 lines of therapy of which at least 1 included targeted therapy. Sequence of lines of therapy and regimens used in first (1L), second (2L), and third (3L), as well as timing of BRAF testing by sequence of therapy were described. In the Truven sample (n=162), targeted therapy was used by 66% in 1L and by 54% in 2L, and 62% had a BRAF test; in the IQVIA RWD Adjudicated Claims – USA sample (n=247), targeted therapy was used by 62% in 1L and by 50% in 2L, and 68% had a BRAF test. Among those with a claim for a BRAF test prior to 1L, over two-thirds were initiated on targeted therapy. These findings suggest that the rate of BRAF testing remained low in the years following the approval of BRAF-targeted regimens for metastatic disease. Given the recently approved adjuvant treatment options for stage III melanoma, improving the rates of BRAF testing becomes increasingly important.

Aim: To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011–2016, and assess outcomes among patients who subsequently received systemic adjuvant therapy versus watch-and-wait. Methods: Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe. Results: Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy. Conclusion: Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.

To compare healthcare resource utilization (HRU) between patients with metastatic melanoma (MM) initiated on first-line (1L) combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (D + T; oral) and those initiated on 1 L monotherapy with the anti-PD1 monoclonal antibodies nivolumab or pembrolizumab (N/P; intravenous).Patients with melanoma initiated on D + T or N/P from Q1/2014 to Q2/2016 (defined as 1 L treatment for MM) were identified in the Truven MarketScan database. Entropy balancing was used to reweight the N/P cohort in order to make it comparable to the D + T cohort with respect to the mean and variance of baseline covariates. HRU outcomes during 1 L therapy, reported per patient-year (PPY), were described and compared between the two cohorts post-weighting (i.e. independently of baseline covariates).Of the 445 patients included, 202 and 243 were initiated on D + T and N/P, respectively. After weighting, patients initiated on N/P had more outpatient visits for drug administration during 1 L therapy than those initiated on D + T (difference = 18.6 visits PPY [95% CI = 16.0-21.1]). Patients initiated on N/P also had more outpatient office visits for reasons other than drug administration (difference = 8.1 visits PPY [95% CI = 1.9-13.7]). No significant differences were observed for other HRU parameters (i.e. inpatient admissions, inpatient days, and emergency department visits during 1 L therapy).HRU during 1 L therapy was generally similar between patients initiated on D + T and N/P. Nonetheless, patients initiated on N/P had more outpatient visits, including more outpatient visits for reasons unrelated to drug administration.

Objective To compare kidney size (used as proxy for total renal angiomyolipoma [rAML] size) and kidney function outcomes between patients with tuberous sclerosis complex (TSC) and rAML treated and not treated with everolimus. Methods Medical charts of adults with TSC-associated rAML followed at a specialty medical center in the Netherlands (1990–2015). Included patients treated with everolimus (n = 33, of which 27 were included in the kidney size analyses and 27 in the kidney function analyses [21 patients in both]; index date = everolimus initiation) and non-treated patients (n = 39, of which 29 were included in the kidney size analyses and 33 in the kidney function analyses [23 patients in both]; index date = one date among all dates with outcome measurement).Percent change in kidney size and kidney function from the index date to the best measurement in the two years post-index date (best response) compared between patients treated and not treated with everolimus. Results Compared with non-treated patients, significantly more everolimus-treated patients experienced a reduction in the size of their largest kidney in the two years post-index date (85.2% vs. 37.9%, p < 0.01). Also, there was a tendency towards more improvement in the estimated glomerular filtration rate (eGFR) among the everolimus-treated patients (55.6% vs. 33.3%, p = 0.08). Conclusions The study results suggest that everolimus is effective in controlling and even reversing the growth of the kidneys, used as a proxy for rAML size, as well as preserving or improving kidney function in patients with TSC and rAML treated in a real-world, observational setting.

Background Trastuzumab reduces the risk of relapse in women with HER2+ early stage breast cancer. Yet, little information exists on the timing of trastuzumab initiation and its association with relapse and survival outcomes in these patients. The study aimed to investigate the impact of delaying the initiation of adjuvant trastuzumab treatment for >6 months on time to relapse, overall survival, and relapse-free survival among patients with HER2+ early stage breast cancer who did not receive neoadjuvant therapy. Methods Adult women initiating trastuzumab adjuvant therapy within 1 year of breast cancer surgery who did not receive neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012 (N = 2,749). By design, participants had to be alive and relapse-free at the time they initiated adjuvant trastuzumab. Patients were classified into two groups based on the time from breast cancer diagnosis to trastuzumab initiation: ≤6 months and >6 months. An algorithm based on secondary neoplasm ICD9 codes along with treatment gaps and initiations was used to identify relapses. Percent relapses and/or deaths were reported by study groups and compared using χ2 tests. The impact of delaying trastuzumab initiation on time to relapse, overall survival, and relapse-free survival was estimated from Cox regression models adjusted for age, overall comorbidity profile at the time of the BC diagnosis (Charlson index), type of surgery (breast conserving vs. breast removing), and radiotherapy (prior to the initiation of trastuzumab). In all three Cox models the follow-up started at adjuvant trastuzumab initiation. Results Of 2,749 women who met the selection criteria, 79.3% initiated adjuvant trastuzumab ≤6 months of diagnosis and 20.7% initiated adjuvant trastuzumab >6 months after the diagnosis (Table). Patients who delayed the initiation of trastuzumab for >6 months were younger (57.2% aged 6 months after diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab ≤6 months of diagnosis in both unadjusted and adjusted analyses (Table). N events (% events)Hazard Ratio (95% CI) ≤6 months group N = 2,180>6 months group N = 569p-value>6 months group vs ≤6 months groupRelapse outcome333 (15.2%)134 (24.3%)< .0011.40 (1.14 - 1.72)*Death outcome (overall survival)138 (6.3%)64 (11.6%)< .0011.44 (1.06 - 1.96)*Relapse or death outcome (Relapse-free survival)386 (17.6%)148 (26.8%)< .0011.33 (1.09 - 1.61)**p-value < .05 Conclusions The results of this population-based study among patients with HER2+ early stage breast cancer who did not receive neoadjuvant therapy suggest that delays of over 6 months in the initiation of trastuzumab among HER2+ early stage breast cancer patients are associated with a higher risk of relapse and shorter overall survival and relapse-free survival. Disclaimer Research derived from an IRB approved protocol at Naval Medical Center Portsmouth, VA. The views expressed in this abstract are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, Department of the Navy, Department of Defense or the United States Government. Dr. C.G. and Dr. K.M. are members of the U.S. military. This work was prepared as part of their official duties. Title 17 U.S.C. 105 provides that 'Copyright protection under this title is not available for any work of the United States Government.' Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties. Citation Format: Christopher M Gallagher, Kenneth More, Anthony Masaquel, Tripthi Kamath, Annie Guerin, Raluca Ionescu-Ittu, Marjolaine Gauthier-Loiselle, Roy Nitulescu, Nicholas Sicignano, Brian Barnett, Eric Wu. Delay in trastuzumab initiation leads to decreased overall survival in patients with HER2+ early stage breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-21-03.

Objective The use of bevacizumab in advanced non-squamous non-small cell lung cancer (NSCLC) is controversial among elderly patients. This study aimed to compare overall survival for Medicare patients diagnosed with NSCLC and treated with either first-line bevacizumab–carboplatin–paclitaxel (BCP) or carboplatin–paclitaxel (CP). Methods Patients ≥65 years old, first diagnosed with non-squamous NSCLC stage IIIB/IV between 2006 and 2009, and treated with either first-line BCP or CP, were selected from the SEER-Medicare database that links cancer registry and US Medicare claims data. Kaplan–Meier estimates were used to evaluate survival. Multivariable Cox proportional hazards models were used to compare the effect of BCP versus CP on the hazard of death. Age-stratified analyses were conducted for patients aged 65–74 and ≥75 years. Results Of 1706 patients in the study sample, 592 (34.7%) received BCP and 1114 (65.3%) received CP; 692 (40.6%) were ≥75 years. Adjusted median survival time in the BCP versus CP cohorts was 10.5 versus 8.5 months ( p =0.008). The difference in median survival favoring the BCP cohort was statistically significant for both patients aged ≥75 years (2.8 months, p =0.019), and patients aged 65–74 years (1.5 months, p =0.018). The adjusted hazard of death did not differ between the cohorts (HR: 0.96, 95% CI: 0.86–1.06); however, during the first year of follow-up, when most deaths (>60%) occurred, the hazard of death was 18% lower for the BCP cohort (HR: 0.82, 95% CI: 0.71–0.94). BCP patients also had 18% fewer hospital admissions than CP patients (adjusted incidence rate ratio (IRR): 0.82, 95% CI: 0.72–0.94) and 23% fewer inpatient days (IRR: 0.77, 95% CI: 0.65–0.91). Conclusions In this retrospective analysis of Medicare patients in the SEER database, first-line therapy with BCP was associated with longer survival and fewer hospitalizations than CP.

Background— Our objective was to obtain contemporary lifetime estimates of congenital heart disease (CHD) prevalence using population-based data sources up to year 2010. Methods and Results— The Quebec CHD database contains 28 years of longitudinal data on all individuals with CHD from 1983 to 2010. Severe CHD was defined as tetralogy of Fallot, truncus arteriosus, transposition complexes, endocardial cushion defects, and univentricular hearts. We used latent class bayesian models combining case definitions from physician claims, hospitalization, and surgical data to obtain point and interval prevalence estimates of CHD in the first year of life, in children ( Conclusions— With an increase of >50% in CHD prevalence since 2000, by 2010 adults accounted for two thirds of patients with severe and other forms of CHD in the general population. Our findings should inform allocation of resources and the planning of workforce needs for the predominantly adult CHD population.

To describe the distribution of costs and to identify the drivers of high costs among adult patients with type 2 diabetes mellitus (T2DM) receiving oral hypoglycemic agents.T2DM patients using oral hypoglycemic agents and having HbA1c test data were identified from the Truven MarketScan databases of Commercial and Medicare Supplemental insurance claims (2004-2010). All-cause and diabetes-related annual direct healthcare costs were measured and reported by cost components. The 25% most costly patients in the study sample were defined as high-cost patients. Drivers of high costs were identified in multivariate logistic regressions.Total 1-year all-cause costs for the 4104 study patients were $55,599,311 (mean cost per patient = $13,548). Diabetes-related costs accounted for 33.8% of all-cause costs (mean cost per patient = $4583). Medical service costs accounted for the majority of all-cause and diabetes-related total costs (63.7% and 59.5%, respectively), with a minority of patients incurring80% of these costs (23.5% and 14.7%, respectively). Within the medical claims, inpatient admission for diabetes-complications was the strongest cost driver for both all-cause (OR = 13.5, 95% CI = 8.1-23.6) and diabetes-related costs (OR = 9.7, 95% CI = 6.3-15.1), with macrovascular complications accounting for most inpatient admissions. Other cost drivers included heavier hypoglycemic agent use, diabetes complications, and chronic diseases.The study reports a conservative estimate for the relative share of diabetes-related costs relative to total cost. The findings of this study apply mainly to T2DM patients under 65 years of age.Among the T2DM patients receiving oral hypoglycemic agents, 23.5% of patients incurred 80% of the all-cause healthcare costs, with these costs being driven by inpatient admissions, complications of diabetes, and chronic diseases. Interventions targeting inpatient admissions and/or complications of diabetes may contribute to the decrease of the diabetes economic burden.

Objectives Patient-centered care and patient satisfaction represent key dimensions of health care quality. This is relevant for the growing number of patients with life-long conditions. In the present study, our goal was to examine clinicians' attitudes and behavior with respect to patient satisfaction in adult congenital heart disease outpatient clinics. Methods A 34-question survey was developed to assess adult congenital heart disease clinicians' awareness, attitudes, and behavior relative to patient satisfaction and administered in-person or online to clinicians from the largely U.S.-based Adult Congenital Heart Association's database of adult congenital heart disease health care providers. Results Overall, 267 questionnaires were filled out: 108 were collected in person (79% response rate) and 159 online (17.5% response rate). Responses were received from physicians (161); nurses (73); physician assistants (20); and others (13). Although 85% of clinicians believed it was important to inquire about patient satisfaction, only 28% reported routinely inquiring about this dimension of care. Only 34% claimed they had adequate training to cope with varying levels of patient satisfaction, 44% stated that their department utilized patient satisfaction surveys, and 37% received feedback from the hospital management in the preceding 12 months. In multivariate analyses, clinicians that received feedback from the hospital management and had adequate training were more likely to inquire about patient satisfaction. Conclusion Although patient satisfaction is perceived as an important dimension of quality care by adult congenital heart disease clinicians, most of them reported insufficient institutional support to achieve this. Our findings suggest that clinicians would benefit from health care organizations engaging them in the delivery of this dimension of health care quality.

Background The most common congenital anomaly in adults is secundum atrial septal defect (ASD), which can be closed using a surgical or transcatheter approach. Despite the growing use of transcatheter ASD closure, few studies have examined the cost-effectiveness of this strategy. We sought to compare the long-term cost effectiveness of transcatheter and surgical closure of secundum ASD in adults. Methods A decision-analytic model was used with all clinical outcome parameter estimates obtained from the province-wide Quebec Congenital Heart Disease Database. Costs were obtained from a single academic centre (Canadian dollars). A cost-effectiveness analysis using a discrete event Monte Carlo simulation model from the perspective of a single third party payer and multiple sensitivity analyses were performed. Patients were followed for a maximum of 5years after ASD closure. Results Between l998 and 2005, we identified 718 adults (n=335 transcatheter; n=383 surgical) who underwent ASD closure in Quebec. The 5-year cost of surgical closure was $15,304 SD $4581 versus $11,060 SD $5169 for the transcatheter alternative. At 5years, transcatheter closure was marginally more effective than surgery (4.683 SD 0.379 life-years versus 4.618 SD 0.638 life-years). Probabilistic sensitivity analyses demonstrated that transcatheter ASD closure was a dominant strategy with an 80% probability of cost savings and equal or greater efficacy compared to surgical treatment. Conclusion Although definitive conclusions are limited given the observational nature of the primary data sources, transcatheter ASD closure appeared to be a cost-effective strategy associated with slightly improved clinical outcomes and reduced costs compared to surgical closure at 5-years follow-up.

e22527 Background: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive and debilitating tumor that generally affects young working-age adults. This study assessed work productivity loss in TGCT patients. Methods: Incident patients aged 18-64 years with diagnosis of TGCT, who had earning and disability data, were identified in the OptumHealth database (Q1 1999 – Q1 2017). Patients were classified into surgical and non-surgical groups depending on the presence of joint surgery claim in postindex period. Control patients without TGCT were matched 10:1 with TGCT patients on age, gender, year of TGCT diagnosis, and follow-up duration. The number of days missed from work due to disability and medical visits post diagnosis was compared using Poisson regressions. General linear models were used to compare indirect costs associated with productivity loss. Results: A total of 1,395 TGCT patients (724 surgical; 671 non-surgical) were matched to 13,950 controls (36% female; mean age = 47 years). Both surgical and non-surgical TGCT patients had more comorbidities (mean Charlson Comorbidity Index (CCI): 0.3 vs 0.2; 0.4 vs 0.2; p < 0.001), had greater use of analgesic drugs (44% vs 20%; 40% vs 21%; p < 0.001) and MRI tests (47% vs 4%; 26% vs 3%; p < 0.001) in the 12 months before TGCT diagnosis compared with controls. Both surgical and non-surgical TGCT patients missed more time from work due to disability and medical visits and had higher indirect cost associated with productivity loss than matched controls. Disability burden was greater in patients receiving surgery. Conclusions: Regardless of receiving surgery or not, TGCT is associated with significant work productivity loss. These findings highlight the unmet need for effective treatments to reduce disability and restore function in TGCT patients. [Table: see text]

Acute heart failure (AHF) hospitalizations pose significant economic burden, yet outcomes by treatment (tx) patterns are not well described. We described real-world tx patterns and the associated outcomes of hospitalized patients (pts) with AHF and reduced ejection fraction (rEF; LVEF≤40%) in US