tbuckley/cabot-search huggingface dataset:
Trends in Prices of Popular Brand-Name Prescription Drugs in the United States
Authors: Nathan E. Wineinger, Yunyue Zhang, Eric J. Topol
Journal: JAMA Network Open (2019)

<h3>Importance</h3> High and continually increasing pharmaceutical drug spending is a major health and health policy concern in the United States. <h3>Objective</h3> To demonstrate trends in prices among popular brand-name prescription drugs. <h3>Design, Setting, and Participants</h3> This economic evaluation of drug prices focuses on 49 top-selling brand-name medications in the United States. Pharmacy claims data from January 1, 2012, through December 31, 2017, were obtained from Blue Cross Blue Shield Axis, a database that includes data from more than 35 million individuals with private pharmaceutical insurance. Drugs that exceeded $500 million in US sales or $1 billion in worldwide sales were examined. <h3>Main Outcomes and Measures</h3> The median sum of out-of-pocket and insurance costs paid by patients or insurers for common prescriptions, presented annually and monthly, was the primary outcome. <h3>Results</h3> In total, 132 brand-name prescription drugs were identified in 2017 that met the inclusion criteria. Of this total, the study focused on 49 top-selling drugs that exceeded 100 000 pharmacy claims. Substantial cost increases among these drugs was near universal, with a 76% median cost increase from January 2012 through December 2017, and almost all drugs (48 [98%]) displaying regular annual or biannual price increases. Of the 36 drugs that have been available since 2012, 28 (78%) have seen an increase in insurer and out-of-pocket costs by more than 50%, and 16 (44%) have more than doubled in price. Insulins (ie, Novolog, Humalog, and Lantus) and tumor necrosis factor inhibitors (ie, Humira and Enbrel) demonstrated highly correlated price increases, coinciding with some of the largest growth in drug costs. Relative price changes did not differ between drugs that entered the market in the past 3 to 6 years and those that have been on the market longer (number of drugs, 13 vs 36; median, 29% increase from January 2015 through December 2017;<i>P</i> = .81) nor between drugs with or without a Food and Drug Administration–approved therapeutic equivalent (number of drugs, 17 vs 32; median, 79% vs 73%;<i>P</i> = .21). Changes in prices paid were highly correlated with third-party estimates of changes in drug net prices (ρ = 0.55;<i>P</i> = 3.8 × 10<sup>−5</sup>), suggesting that the current rebate system, which incentivizes high list prices and greater reliance on rebates, increases overall costs. <h3>Conclusions and Relevance</h3> The growth of drug spending in the United States associated with government-protected market exclusivity is likely to continue; greater price transparency is warranted.
Using Social Media To Increase HIV Testing Among Men Who Have Sex with Men — Beijing, China, 2013–2017
Authors: Liming Wang, Dylan Podson, Zihuang Chen, Hongyan Lu, Vania Wang, Colin Shepard, John K. Williams, Guodong Mi
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

The prevalence of human immunodeficiency virus (HIV) infection in China is low overall (0.06%) (1); however, it is substantially higher (8.0%) among men who have sex with men (MSM) (2), and the stigmatization of same-sex behaviors in China presents challenges for HIV prevention and treatment efforts. In 2015, Blued, a Beijing-based media company that operates an online dating application popular among Chinese MSM, launched an ongoing HIV testing campaign that combined its push-notification† platform and geolocation capabilities to encourage HIV testing among MSM in Beijing. To assess trends in use of HIV testing services, Blued and CDC's China HIV program examined testing at six Blued-operated Beijing HIV testing centers from 2 years before the campaign launch in 2015 through December 31, 2017. A sharp increase in HIV testing followed the launch of Blued's online campaign, indicating that leveraging social media platforms and their geolocation-based text messaging functionality might be useful in increasing HIV testing among MSM, particularly those aged ≤35 years.
Impact of immune-related adverse events on survival in patients with metastastic urothelial carcinoma treated with immune-checkpoint inhibitors.
Authors: Rafael Morales-Barrera, Cristina Suarez Rodriguez, Macarena Gonzalez, Javier Ros, Maria Eugenia Semidey, Ester Serra Hernandez, Joaquin Mateo, Carlos Fernández Sáez, Fernando Lozano, Richard Mast, Sarai Roche, Angela Quintana, Sara Gutiérrez Fernández, Cesar Serrano, Claudia Valverde, Ines de Torres, Xavier Maldonado, Juan Morote, Joan Carles
Journal: Journal of Clinical Oncology (2019)

4531 Background: Immune-checkpoints inhibitors (ICIs) represents the standard of care for platinum-pretreated advanced urothelial cancer patients (pts). By enhancing T-cell activation, a unique spectrum of inflammatory side effects has emerged, also known as immune-related adverse events (irAEs). Data regarding the association between irAEs and pts outcomes are conflicting. Here we conducted a retrospective analysis to investigate the association between irAEs profile and disease outcome in metastastic urothelial carcinoma (mUC) pts. Methods: Medical records from pts with mUC included in clinical trials between July 2013 and June 2018 and treated with ICIs were reviewed. Pts previously treated with platinum-based chemotherapy or cisplatin ineligible pts who had not been previously treated with chemotherapy were included. Clinical responses were assessed as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST v1.1. Adverse events were graded based CTCAE v4.03. Overall survival (OS) was calculated from the date of initiation of ICI to the date of death. X 2 test was used to determine differences in rates. OS was estimated using Kaplan-Method and long rank test was used to assess differences between groups. All analyses were performed using SPSS v21. Results: From a total of 52 pts, 44 (84.6%) were treated with ICI monotherapy and 8 (15.3%) in combination (anti-CTLA4 or targeted therapy). Median age was 65 years, 42 pts (80.8%) were male, 44 patients (84.6%) had ECOG PS 0-1, 14 pts (26.9%) had liver metastasis. Overall irAEs were observed in 30 pts (57.7%) and 10 pts (19.2%) developed grade 3/4 irAES. Most common grade 3/4 irAEs were diarrhea (6.6%), rash (6.6%) and hepatitis (6.6%). Disease control rate (CR [26%]+PR[33%]+SD[20%]) was higher for patients with irAEs compared to those patients who did not developed irAEs (CR [13.6%]+PR[0%]+SD[22.7%], this difference was statically significant (P = 0.002). Median OS was 11.23 mo (CI 95%, 3.76-18.70) for the overall cohort, while median OS was 21.91 mo for those patients with irAEs compared to 6.47 mo in patients who did not developed irAEs (P = 0.004). Conclusions: In this analysis we found that the development of irAEs was a strong predictor of improved OS in mUC patients treated with ICI.
Genomic characterization of lung tumors and metastatic (Met) sites in advanced (Adv) NSCLC.
Authors: Melinda D Willard, Emily Nash Nash Smyth, Ramon Velasquez Tiu, Julie Beyrer, Yajun Emily Zhu, Lee Bowman, Kristin M Sheffield, Yimei Han, Priscilla Brastianos
Journal: Journal of Clinical Oncology (2019)

2014 Background: Molecular alterations (MA) found in brain (Br) mets of NSCLC pts can differ from primary and/or other met sites, which may explain why therapies targeting primary tumors are less effective at preventing and treating intracranial disease. We analyzed the frequency of known driver genes in adv NSCLC pts and the association with overall survival (OS). Methods: This retrospective observational study identified pts from the Flatiron- Foundation Medicine NSCLC Clinico-Genomic Database who were diagnosed with adv NSCLC from 1 Jan 2011 to 31 Oct 2017 and had tumor tissue analyzed at any time following initial diagnosis via targeted DNA sequencing by FoundationOne. Descriptive statistics summarized MA from lung and met sites (Br and non-brain [NB]). OS was measured from adv diagnosis to death or last activity date (censored). Multivariable Cox proportional hazard regression model was used for time-to-event analysis. Results: Of 3257 pts, data were available from lung (n = 1621), Br (n = 180), and NB sites (n = 377): liver (n = 167), bone (n = 124), adrenal (n = 63), and spine (n = 23). Median age at adv diagnosis was 66.2 yrs. TP53(63.3%), KRAS(28.8%), EGFR(15.6%), STK11 (13.5%), and CDKN2A(8.5%) were frequently mutated genes in lung samples. Genes for Br vs NB sites included TP53(70.6%; 64.7%), KRAS(36.1%; 26.5%), EGFR (9.4%; 18.8%), STK11 (18.9%; 12.7%), and CDKN2A(6.1%; 10.1). KEAP1alterations were also present in 10% (Br), 7.4% (NB), and 6% of lung samples. In treated pts, lack of alterations in select genes ( STK11, TP53, KEAP1) was associated with longer OS, whereas lack of other alterations ( ARID1A, EGFR, ALK, ROS1) was associated with a shorter OS (p &lt; 0.05). Patients with select mutations co-occurring with KRAS had higher risk of death compared to those with KRAS only (p &lt; 0.05). Conclusions: Based on pts with NSCLC whose tumor tissue underwent DNA sequencing, the most frequently altered genes in lung and Br samples included TP53, KRAS, EGFR, STK11, and CDKN2A, with some being significantly associated with OS. Prognosis of NSCLC pts depends on clinical, demographic, and genomic factors and should be carefully considered to optimize clinical outcome.
Comparison of Surgical and Transcatheter Aortic Valve Prostheses
Authors: Francesco Pollari, Theodor Fischlein, Steffen Pfeiffer
Journal: Journal of the American College of Cardiology (2019)

The interest in applying transcatheter aortic valve replacement (TAVR) in lower-risk patients with longer life expectation and the concerns about the durability of TAVR prostheses are a driving issue. In this context, the report from Sondergaard et al. [(1)][1] in a recent issue of the Journal
Breast cancer-specific survival outcomes among patients based on 21-gene recurrence score.
Authors: Wade T. Swenson, Shantanu Mallick
Journal: Journal of Clinical Oncology (2019)

537 Background: The 21-gene recurrence assay predicts cancer recurrence rates and benefit from adjuvant chemotherapy among patients with hormone-receptor-positive breast cancer. The National Cancer Institute and Genomic Health collaborated to provide Recurrence Score (RS) results to complement data from 17 population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Program. Methods: Using the SEER database with linked RS results, a cohort of female breast cancer patients, age greater than 20 years, was identified by RS (low: &lt; 18, intermediate: 18-30, high: &gt; 30) diagnosed between the years 2004 and 2007. A retrospective analysis was conducted to determine eight-year breast cancer-specific survival rates based on RS and other variables. Results: 10,318 patients were identified in the cohort. 5,194 had a low risk RS; 4,282 had an intermediate risk RS; 872 had a high risk RS. Histologic subtypes were: 7,459 infiltrating ductal carcinoma, 941 mixed infiltrating and lobular carcinoma, 933 lobular carcinoma, 327 mixed infiltrating ductal and other histology, 244 mucinous adenocarcinoma, 101 tubular adenocarcinoma, 45 mixed lobular and other histology, 268 other histologies. 644 low risk RS patients received chemotherapy (12.4%); 1,608 intermediate risk RS patients received chemotherapy (37.8%); 593 high risk patients received chemotherapy (68.0%). The eight-year breast cancer-specific survival rates (with 95% confidence intervals) among low risk RS patients without known chemotherapy administration was 98.9% (98.5, 99.2), and 98.4% (97.0, 99.1) with chemotherapy; intermediate risk RS patients without known chemotherapy was 97.0% (96.2, 97.6), and 96.9% (95.9, 97.7) with chemotherapy; high risk RS patients without known chemotherapy was 89.7% (85.4, 92.8), and 92.9% (90.4, 94.7) with chemotherapy. Conclusions: Among a large cohort of patients identified in a population-based cancer registry between 2004 and 2007, there was no statistically significant difference in eight-year breast cancer-specific survival rates among those who received chemotherapy and those who did not, regardless of RS risk group.
Prediction of neoadjuvant chemotherapeutic efficacy by CTC and cfDNA in patients with locally advanced breast cancer.
Authors: Ge Ma, Jingyi Wang, Xiaoan Liu, Tiansong Xia, Shui Wang
Journal: Journal of Clinical Oncology (2019)

551 Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). Liquid biopsy, including circulating tumor cells (CTCs) and cell free DNA (cfDNA) represent an important paradigm shift in precision medicine. The aim of this study was to estimate the value of CTCs and cfDNA in efficacy prediction of the response to NCT in patients with LABC. Methods: Patients with LABC received EC4-T4 regimen NCT. CTCs and cfDNA obtained at time of biopsy, after first course of NCT and after the last course of NCT. All patients were divided into two groups according to pathological reactivity. A novel SE-iFISH strategy, improved for detection of CTCs, was applied. CTCs(CD45-/CD31-) with different cytogenetic abnormality of aneuploid chromosome 8 and small cell size CTCs (≤5 mm of WBCs) were analyzed separately in LABC patients subjected to NCT for the first time. Plasma DNA biomarkers ALU 111 and ALU 260 elements were evaluated using qRT-PCR. DNA integrity was calculated relative to the breast cancer cell line MCF-7. Clinical significance of diverse subtypes of CTCs and cfDNA was systematically investigated. Results: A total of 45 patients was enrolled in this study. According to the therapy response, 6/45 patients had high response (High-R) and 39/45 patients had low response (Low-R). There were no significant differences in CTC number and small cell size CTC number between High-R and Low-R groups in all three detections. However, the CTC number kept stable in the High-R group, but increased continually during NCT in Low-R group. In 45 patients, the percentage of CTCs with trisomy 8, which were related to cancer metastasis, incresed in the Low-R group at the third dectection. The concentration of cfDNA in all three detections did not indicate outcome of NCT. However, concentration of ALU 111 increased in Low-R patients during NCT. In High-R patients, no significant increase was observed. A CTC and cfDNA panel were constructed to discriminate High-R patients from Low-R patients. The areas under the receiver-operating characteristic (ROC) curves of the pannel for the three times were 0.803, 0.859 and 0.667, respectively. DNA integrity index(CFDI) was significantly higher in High-R group than Low-R after first course of NCT. The areas under the ROC curves of the CFDI for the three times were 0.675, 0.863 and 0.697, respectively. Conclusions: The trend of cfDNA concentration changed resembled to the number of CTCs, small cell size CTCs and triploid CTCs during NCT, and could predict tumor response to ongoing treatment.
FRI0241 PREGNANCY RATES AND PERINATAL OUTCOMES AMONG WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN COMPARISON TO GENERAL POPULATION
Authors: Young Bin Joo, Ki-Jo Kim, Kyung-Su Park, Yune-Jung Park
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) can affect people of all ages, but it occurs most often during childbearing ages. It has been documented that the fertility rates in women with SLE is similar to those without SLE. On the other hand, the pregnancy adverse outcomes are common in pregnant women with SLE. However, the pregnancy rates in women with SLE was not fully understood. In addition, comparison of the pregnancy adverse outcomes with general population is limited. <h3>Objectives:</h3> We estimated the pregnancy rates and adverse pregnancy outcomes in Korean women with SLE and compared them with women without SLE. <h3>Methods:</h3> Among all women aged 15-49 years in the Korean National Health Insurance claim database from January 2013 to December 2015, pregnant women were identified by using ICD-10 code for delivery and abortion. Pregnant women were categorized into women with SLE and control group. Adverse pregnancy outcomes classified into five categories as follows: fetal loss, intrauterine growth retardation (IUGR), preterm delivery, pre-eclampsia or eclampsia, and gestational diabetes mellitus. Crude incidence rates (IRs) of pregnancy and adverse pregnancy outcomes were calculated. Incidence rate ratios (IRRs) of those were estimated and adjusted for age. <h3>Results:</h3> In SLE, 994 pregnancy cases were observed during the study period. The crude estimated IRs of pregnancy were lower in SLE patients than general population (Table 1). Age-adjusted IRR was also lower in SLE patients (Table1). The adjusted-IRR of live birth in SLE pregnant women was 0.92 (95% CI 0.85 - 0.99) compared with control group. The adjusted-IRR of fatal loss, IUGR, and preterm delivery was 1.27 (95% CI 1.11 - 1.45), 4.52 (95% CI 3.45 - 5.91), and 3.25 (95% CI 1.62 - 6.52), respectively. The IRR of pre-eclampsia or eclampsia was 3.21 (95% CI 2.52 - 4.08), but those of gestational diabetes mellitus was not significant (IRR 0.89, 95% CI 0.80 - 1.00). <h3>Conclusion:</h3> Pregnancy rates in SLE women were lower about 30% compared with general population. Pregnancy adverse outcomes were higher in SLE pregnant women with more than 4-fold IUGR and pre-eclampsia/eclampsia, 3.2-fold preterm delivery. <h3>References:</h3> [1] EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017 Mar;76(3):476-485. <h3>Disclosure of Interests:</h3> None declared
Dose-dense early postoperative intraperitoneal chemotherapy in ovarian cancer: Randomized, phase II trial.
Authors: Rongyu Zang, Tingyan Shi, Rong Jiang, Hong Pu, Huijuan Yang, Dongsheng Tu, Zhiyuan Dai, Yulang Cai, Yuqin Zhang, Xi Cheng, Huixun Jia, Ruiqin Tu, Hua-ying Wang, Jie Tang, Yuting Luan, Shumo Cai
Journal: Journal of Clinical Oncology (2019)

5514 Background: Dose-dense early postoperative intraperitoneal chemo (DD-EPIC) had been carried out in advanced ovarian cancer (OC) pts in China over the past three decades but it was not proved by a prospective study. This trial was designed to confirm the benefit of DD-EPIC in delaying progression and improving survival. Methods: In a multicenter, phase 2 trial, pts with FIGO IIIC-IV OC and optimal debulking surgery (residual disease ≤1cm) were randomly allocated to receive 4 doses of weekly DD-EPIC with cisplatin (50mg/m 2 ) and etoposide (100mg/m 2 ) followed by 6 cycles of intravenous (iv) chemo with carboplatin and taxane every 3 weeks (DD-EPIC group), or standard iv chemo alone (iv group). (ClinicalTrials.gov, NCT01669226). Results: Between 2009 and 2015, 218 pts were randomized, of whom 215 initiated treatment (106 to DD-EPIC and 109 to iv; for efficacy analyses). Totally, 36 pts (16·7%) were received neoadjuvant chemo. With a median of 61·9 mos follow-up, 122 pts died (54 in DD-EPIC and 68 in iv group). Remarkable OS benefit of DD-EPIC was recorded (67·5 mos for DD-EPIC vs. 46·3 mos for iv; HR 0·70, 95% CI 0·49-1·00, P=0·047). Pts in DD-EPIC had a significantly increased median PFS compared with those in iv group (21·7 vs. 16·8 mos; HR 0·64, 95% CI 0·47-0·86, P=0·003). Median TFST was 25·1 vs. 18·0 mos in favor of DD-EPIC (HR 0·62, 95%CI 0·46-0·83, P=0·002). Similar findings were detected in TSST (42·2 vs. 29·3 mos; HR 0·66, 95%CI 0·47-0·94, P=0·019). Grade 3 and 4 Leucopenia (53·8% vs. 35·2%), anemia (23·6% vs. 5·6%) and gastrointestinal events (10·4% vs. 1·9%) were more common in DD-EPIC ( P=0·006, P&lt;0·001 and P=0·010, respectively). Ninety-one pts were detected by gBRCA testing, with 25·3% of cases carrying deleterious BRCAm, but PFS and OS benefit were observed in patients with BRCA-wild type (HR 0·46 and 0·55, 95%CI 0·27-0·81 and 0·27-1·11, respectively). Conclusions: DD-EPIC with a higher completion rate and acceptable treatment burden was associated with longer OS than standard iv alone. Owing to the benefit of relatively long-term OS, DD-EPIC may be considered as a valuable option for OC, particularly in developing countries and BRCA-wild type pts. Clinical trial information: NCT01669226. [Table: see text]
30-year extrapolations of overall survival (OS) and metastasis-free survival (MFS) from the SPCG-4 trial of radical prostatectomy (RP) versus watchful waiting (WW) in patients (pts) with early prostate cancer (ePCa).
Authors: Neda Alrawashdh, Mok Oh, Abdulaali Almutairi, Nimer S Alkhatib, Hani M. Babiker, Karen MacDonald, Ali McBride, Ivo Abraham
Journal: Journal of Clinical Oncology (2019)

e16597 Background: Bill-Axelson et al (NEJM, 2014) reported 18 year (y) mortality and metastasis (mets) data on ePCa pts randomized in the SPCG-4 trial to RP (n = 347) vs WW (n = 348) for all pts and by age &lt; 65y (n RP = 157 n WW = 166) vs ≥65y (n RP = 190 n WW = 182). Using the 18y data, we estimated the cumulative incidence, OS and MFS curves, and absolute risk reduction (ARR) for death and mets up to 30y for all pts and pts &lt; 65y vs ≥65y. Methods: Published 18y SPCG-4 cumulative incidence curves for death and mets were digitized and parametric regression models were tested to fit the data. From these we estimated, for death and mets, the respective 30y cumulative incidences, OS and MFS curves with 95%CI; and ARR. ARRs for &lt; 65y and ≥65y were compared using the chi-squared test. Results: The exponential regression model fit the data best. Over the 18 to 30y period, OS in all pts decreased from .81 to .69 in RP and from .72 to .56 in WW; in pts &lt; 65y from .81 to .69 in RP and from .67 to .49 in WW; in pts ≥65y from .83 to .72 in RP and from .78 to .64 in WW. Over the same period, MFS in all pts decreased from .81 to .69 in RP and from .73 to .56 in WW; in pts &lt; 65y from .81 to .69 in RP and from .67 to .49 in WW; in pts ≥65y from .78 to .64 in RP and from .75 to .59 in WW. OS and MFS 95%CI curves overlapped in pts ≥65y but not in pts &lt; 65y. ARRs for death and mets of RP over WW are shown below by 2y interval. ARRs for death and mets were statistically different in pts &lt; 65y but not in pts ≥65y. Conclusions: Extrapolated to 30y post randomization, RP shows better gains in OS and MFS over WW. RP is associated with significant reductions of death and mets: 19 more surviving pts and 20 more metastasis free pts per 100 pts among pts &lt; 65y but not among pts ≥65y. These data enable clinicians to provide ePCA pts considering RP vs WW with up to 30y prognostic information. This facilitates informed patient decision making, especially among those age &lt; 65y. [Table: see text]