bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world examination of remission patterns in patients (pts) with acute myeloid leukemia (AML).
Authors: Tabah Ashley , Huggar David , Brady Brenna L. , Jariwala-Parikh Krutika , Copher Ronda , LeBlanc Thomas William 
Published: May 2020

e19336 Background: For pts with AML, prognosis is poor as long-term remission is elusive and ≥ 60% of pts relapse. The effect of remission status on healthcare resource utilization (HCRU) and costs is unclear. This study assessed administrative claims data from pts with AML to understand the potential benefit of novel, remission-prolonging therapies on HCRU and costs. Methods: Pts with newly diagnosed AML who received frontline therapy and did not undergo hematopoietic stem cell transplantation were identified in the MarketScan Commercial and Medicare Supplemental database from Jan 1, 2012–June 6, 2018. Pts were followed over a fixed 6-month (mos) pre- and variable post-diagnosis period; remission and relapse events were identified by diagnosis codes. Pts were analyzed by duration of remission ( < 3, 3– < 6, 6– < 9, and ≥ 9 mos), based on time from first remission claim to first relapse claim or end of follow up, whichever occurred first. Pt characteristics, relapse, HCRU, and costs were assessed. Results: 459/1003 eligible pts (45.8%) had evidence of remission. Most pts were in remission for < 3 mos (n = 161; 35.1%) or ≥ 9 mos (n = 165; 35.9%); 81 (17.6%) and 52 (11.3%) pts were in remission for 3– < 6 and 6– < 9 mos, respectively. Median follow-up for all pts was 236 days. Across remission cohorts, mean age at diagnosis was 55–59 years and median time to remission (from first AML diagnosis to first remission claim) was 82–90 days. Median time from AML diagnosis to relapse was 265.5 days. Of pts in remission, 30.5% relapsed (41.0%, 28.4%, 40.4%, and 18.2% for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively). From AML diagnosis to the end of follow-up, mean all-cause per pt per mos (PPPM) healthcare costs for all pts were $44,588. Longer durations of remission were associated with reduced mean PPPM costs ($64,188, $53,260, $30,219, and $16,654 for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively); similar trends were observed for AML-related costs. Mean all-cause PPPM costs were also reduced during remission, measured from the first remission claim to the first relapse claim or end of follow-up. A significant decrease was observed for pts in remission for ≥ 6 mos ($35,229, $36,193, $17,486, and $8,933 for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively). Conclusions: In this real-world study, 46% of pts with AML achieved remission after frontline therapy, although durations of remission varied. A longer duration of remission was associated with reduced PPPM costs over the study period indicating a potential economic benefit of remission-prolonging therapies in AML, including maintenance treatments.
Real-life implementation of the SCOT trial findings: An interrupted time series analysis.
Authors: Hanna Catherine , Robles-Zurita Jose Antonio , McLoone Philip , Kelly Caroline , Boyd Kathleen , Jones Robert J. 
Published: May 2020

e19341 Background: The Short Course Oncology Treatment (SCOT) trial demonstrated that three months of adjuvant, doublet chemotherapy for patients with colorectal cancer was non-inferior and significantly less toxic than six months. To understand if and how these results were implemented, this study analysed prescribing practice before and after dissemination of the SCOT results at a population level. Methods: Individual electronic records for patients in a Scottish health board (population 1.1 million) were reviewed (January 2010-June 2019) to explore the proportion of patients receiving over three months of treatment pre and post-SCOT. Logistic and linear regression were used in an interrupted time series analysis to estimate prescribing practices, and to assess the counterfactual situation in which the trial had not occurred. Patients receiving single agent chemotherapy were the comparator group. Predictors of patients receiving a longer duration of treatment post-SCOT were also identified. Results: In total, 998 patients received adjuvant chemotherapy; 564 doublet and 434 single agent. For those prescribed doublet chemotherapy, there was a significant decrease in the proportion receiving more than 3 months of treatment after the SCOT trial results (20%) versus pre-SCOT (84%, p < 0.001). Disease risk was a key predictor for longer duration of treatment post-SCOT. Table outlines the predicted practice post-SCOT (June 2019) for the modelled and counterfactual scenarios. Conclusions: A clear change in treatment duration for patients receiving doublet chemotherapy was observed. Disease stage influencing post-SCOT prescribing aligns with recently updated clinical guidelines. This methodology can be applied to explore the implementation of future trials and to highlight any barriers to implementation that exist. [Table: see text]
Patterns of hedgehog inhibitor (HHI) treatment interruptions and re-initiations among patients with basal cell carcinoma (BCC) in real-world clinical practice.
Authors: Jalbert Jessica J. , Chen Chieh-I , Wu Ning , Fury Matthew G. , Ruiz Emily S , Ge Wenzhen 
Published: May 2020

e19349 Background: HHIs are oral targeted therapies approved for the treatment of advanced BCC but treatment-related adverse events may result in treatment interruptions or discontinuation. The objective of this study was to describe HHI treatment patterns among patients with BCC in real-world clinical practice. Methods: We conducted an observational cohort study using MarketScan Commercial/Medicare databases (01/01/2013–09/30/2018). We identified new users of HHIs (index date = date of the first dispensation), ≥18 years of age who were continuously enrolled for ≥6 months prior to the index date (i.e. baseline) with ≥1 baseline BCC diagnosis. Treatment interruptions (TI) were defined as a lack of dispensation following the exhaustion of days’ supply and allotted grace period (GP). Re-initiation (RI) was defined as ≥1 HHI dispensation after TI. The Kaplan–Meier method was used to estimate risk and time to TI and, among patients with a TI, incidence of RI. HHIs are generally dispensed in 30-days’ supply and indicated as long as a patient derives a clinical benefit; however, since TIs are commonly employed during HHI therapy, sensitivity analyses were conducted using GPs of 14, 30, 60, 90, and 120 days. Results: We identified 469 patients with a BCC diagnosis initiating HHIs. The mean (SD) age was 67.6 (15.8) years, 64.2% were men, 51.2% were covered by commercial insurance, and 99.2% initiated vismodegib. Using a GP of 14, 30, 60, 90, and 120 days, the risk of TI was 79.2%, 68.8%, 60.0%, 55.4%, and 51.4% at 6 months and 94.8%, 91.3%, 88.2%, 83.2%, and 80.2% at 1 year, respectively. Median HHI treatment duration ranged from 94 days (95% CI: 90–109) using a GP of 14 days to 173 days (95% CI: 156–194) using a GP of 120 days. At 6 months following TI, incidence of RI was 35.8%, 19.8%, 11.3%, 6.9%, and 4.9% using a GP of 14, 30, 60, 90, and 120 days, respectively. The incidence of HHI RI at 1-year following TI ranged from 40.8% using a 14-day GP to 13.4% using a 120-day GP. Conclusions: Median HHI treatment duration was approximately 6 months, even after allowing for a 120-day GP. Median treatment duration was considerably shorter than what has been reported in clinical trials. Our results suggest that long-term HHI therapy may be difficult in a real-world setting.
Safety and outcomes of immunotherapy re-challenge in lung cancer.
Authors: Nan Xinyu , Gabbai-Saldate Paulette , Patel Sandip Pravin , Bazhenova Lyudmila , Mitchell William M. , Gold Kathryn A. 
Published: May 2020

e19355 Background: Immune checkpoint inhibitors (CIs) have been shown to improve overall survival in lung cancer and are FDA approved in multiple settings, both as single agents and in combination with chemotherapy. Immune related adverse events (irAEs) are common and frequently manifest as dermatitis, pneumonitis, colitis, and hepatitis, among others. Managing grade 2 or higher irAEs often requires multiple outpatient visits and sometimes inpatient admissions, which can significantly increase patient morbidity and healthcare cost. There is limited evidence on the safety of restarting CIs after moderate to severe irAE. Identifying high-risk factors for developing severe irAEs again after re-challenge can improve patient care and cost efficiency. Methods: We searched our electronic medical records to identify patients with NSCLC and SCLC treated with one or more PD-1, PD-L1, or CTLA-4 CIs at our institution between 2013 and 2019. We reviewed 452 patients and identified 44 patients who developed irAE requiring treatment discontinuation. Of these 44 patients, 19 were re-challenged with same or different CIs. The primary end point of this study is to assess the rate of grade 2 or higher irAE after CI re-challenge. Secondary endpoints are mortality rate, overall survival, and disease status. Results: Median follow up for the 19 patients who were re-challenged with CI was 15 months. Median duration of CI treatment after re-challenge was 6 months (range 0.5 to 25 months). 7 patients (37%) developed irAEs (grade 2 or above) again (5 pts with same irAE as prior). Multivariate logistic regression analysis revealed that age≥70 and requirement of steroid for initial irAEs were associated with a higher risk of recurrent irAEs. Median overall survival has not yet been reached; 32% of patients have died. No deaths were related to irAE. After re-challenge with CIs, 42% of the patients had partial response or stable disease, and 58% had progression of disease. Conclusions: Our study demonstrated that re-challenge with immunotherapy is feasible in some patients who had treatment held due to irAEs, though recurrent irAEs were common. Caution should be taken when restarting CIs after moderate to severe toxicities, especially in older adults.
Phyllodes tumor of breast, real-world data from a referral center in Mexico.
Authors: Contreras-Salcido María Inés , Salazar-Mejía Carlos Eduardo , González-Gutiérrez Adriana , Martinez Rolando Jacob , Lara-Campos Jackeline Grace , Gonzalez Vela Jose Luis , Llerena Edio , Vidal-Gutiérrez Oscar , Hernández-Barajas David , González-Guerrero Juan Francisco 
Published: May 2020

e19356 Background: Phyllodes tumors of breast (PTB) comprise a wide range of rare fibroepithelial neoplasms representing less than 1% of all breast tumors. Studies that describe the clinical characteristics of Mexican women with PTB are scarce. Methods: We performed a retrospective analysis of all patients with newly diagnosed PTB treated at an oncology referral center in Northeast Mexico from 2013 to 2018. Results: Twenty-three women were included in the analysis. Median age at diagnosis was 51 years. Diagnosis was made by self-detection in all cases, with a median tumor size of 12.8 cm. Approximately 26% of patients had a history of benign breast disease. Regarding treatment received 39% underwent radical mastectomy whereas simple mastectomy and breast-conserving surgery were performed in 39 and 22%, respectively. PTB were classified as benign, borderline, and malignant in 17, 13, and 70% of cases, respectively. Patients with malignant PTB showed a heterologous component in 22% of cases (60% with mixed histology, 20% fibromyxosarcoma, and 20% osteosarcoma). Metastatic disease at diagnosis was documented in 3 patients. Relapse of disease was confirmed in eight patients, two of them corresponded with borderline histology and six to malignant subtype. Recurrence sites by frequency were locoregional only 38%; distant disease to the lungs only 12%; and combined metastases to lung, liver and central nervous system 50%. Regarding management of recurrence, four patients received chemotherapy, two received only radiotherapy, one was treated with radiotherapy and chemotherapy and one woman received surgical treatment with adjuvant radiotherapy. Among all patients analyzed, the median overall survival was 23.6 months. Conclusions: To our knowledge, this is one of the first studies analyzing the clinical-pathological characteristics of phyllodes tumors in the Mexican population.
Preventable patient acute mortality after EMR-generated QTc alerts.
Authors: Bleiberg Benjamin Aaron , Yan Jingsheng , Xie Donglu , Lightfoot Tammy , Zhu Hong , Reisch Joan , Sher David , Chandra Alvin , Terauchi Stephanie , Gerber David E. , Khan Saad A. 
Published: May 2020

e19359 Background: EMR generated QTc prolongation alerts are ubiquitous in cancer patients. Their significance and impact on mortality is unknown. Methods: From 2006-2018, 19,223 adult cancer patients at UT-Southwestern hospitals had EMR generated QTc prolongation drug alerts. We collected information on cancer site, demographics and alert details. Deaths ≤10 days from a first QTc alert (acute mortality) were considered more attributable to QTc prolongation. We analyzed overall patient survival through multivariable Kaplan-Meier analysis and Cox regression with the two-outcomes (dead/alive) using a ≤10 days cutoff and followed patients for 365 days from their 1st alert. Results: Analysis of mortality from 1st QTc alert demonstrated statistically significant (p = < 0.05) higher risk of ≤10-day mortality in: patients age > 70 yrs, hazard ratio (HR) = 2.32; black, HR = 1.26 or other/unknown race, HR = 1.29; and increasing number of QTc alerts, particularly patients with 6-10, HR = 1.67 or > 11 HR = 1.88 alerts. Females had lower mortality compared to males, HR = 0.83. Compared to a head and neck cancer patient baseline, significantly increased ≤10-day mortality was seen in: GI, HR = 2.16; lung, HR = 1.94; blood, HR = 1.46; soft tissue, HR = 2.26; and female genital, HR = 1.55 cancers. Male genital, HR = 0.39; breast, HR = 0.57; and endocrine, HR = 0.48 cancers had significantly decreased ≤10-day mortality. In patients with EKG’s recorded: 34 males who died ≤10-days of their 1st alert had significantly longer QTc intervals compared the 5465 who survived to day 11 (469 vs 450 msec, p = < 0.0001). There was no QTc prolongation in the 24 females who died ≤10-days compared to the 4392 who survived to Day 11. Deaths ≤10 days after a QTc alert were rare (total 149/19,223; range 0.01 for male genital to 2.5% for GI), while the majority of deaths within 1 year of a patient’s 1st alert occurred between 11-180 days (range 1.03% for endocrine to 11.05% for lung). Most patients were alive > 1 year after their 1st alert: 63.77% (lung)-95.9% (endocrine). Conclusions: Patients with EKG-proven prolongation of QTc intervals after QTc alerts likely represent a segment of the population where intervention may reduce acute mortality. It is unclear whether the QTc interval prolongation is the actual cause of death or if the EMR alerts identify patients with co-morbidities associated with high risk of acute mortality.
Comparison of treatment costs of pembrolizumab versus nivolumab in head and neck squamous cell carcinoma.
Authors: Yeh Justin , Guddati Achuta Kumar 
Published: May 2020

e19368 Background: Pembrolizumab and Nivolumab are PD-1 inhibiting immunotherapy agents approved for the treatment of metastatic or recurrent head and neck squamous cell carcinoma in patients previously treated with platinum-based chemotherapy. Both therapies have demonstrated similar survival benefits and adverse event profiles, but there is no published comparison of treatment cost and survival between the two agents. This study aims to analyze the cost-effectiveness of pembrolizumab compared to nivolumab through network meta-analysis techniques. Methods: Data published from the KEYNOTE-040 (pembrolizumab) and CheckMate 141 (nivolumab) studies were used to generate a model incorporating the cost of each drug in both the arms. The cost of treatment of side effects was extracted from previously published data and used for cost estimation in the model. Data from the standard of care arms (cetuximab, methotrexate, or docetaxel) in each study were adjusted to provide a common reference between the two studies. The number of years added in terms of overall survival was calculated for the entire experimental arm and the cost of each such year was calculated. All costs were adjusted for inflation. Results: Using published data from the KENOTE-040 trial, the average cost per patient adjusted for inflation over time, over 24 months in the pembrolizumab arm was $159,302, and similarly using data from the Checkmate 141 trial, the average cost per patient over 18 months in the nivolumab arm was $118,790. The cost of management of adverse effects was $18,728 vs $16,685 (pembrolizumab vs. nivolumab) during these time periods. Our model suggests that the adjusted total cost per month for patients on these drugs is very similar: $7417.91 vs. $7526.38. Assuming that the quality of life was similar in both groups and using an average OS for the standard of care arms, our model predicts that ICER for pembrolizumab is higher than nivolumab ($203,085 vs. 132,644). Conclusions: Both pembrolizumab and nivolumab improve survival benefit compared to their respective standard of care arms. However, the ICER for both medications is higher than the threshold set by many payers and health provider organizations. The model makes several assumptions which may render it less accurate to compare between trials but the cost of treatment for both drugs is not in the cost-effective range. To utilize these drugs in a cost-conscious practice, further research is needed to investigate lower doses at a slower frequency along with reduction of the price for each medication.
Simulation modeling of budget-neutral expanded access to antineoplastic therapy from cost-savings derived from conversion to biosimilar pegfilgrastim-cbqv for the prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) in early-stage breast cancer.
Authors: McBride Ali , MacDonald Karen , Abraham Ivo 
Published: May 2020

e19371 Background: Biosimilars not only have the potential to reduce the cost of prophylaxis of CIN/FN but such savings could be reallocated to provide access to anti-neoplastic treatment. To demonstrate this, we simulated in a 20,000-patient panel: 1) the savings that could be realized from CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv over reference pegfilgrastim with or without on-body injector (PEG/PEG-OBI), 2) a model of expanded access to adjuvant chemotherapy with doxorubicin/cyclophosphamide for localized breast cancer from cost-savings achieved from conversion from PEG/PEG-OBI, and 3) the number-needed-to-convert (NNC) to biosimilar pegfilgrastim-cbqv from PEG/PEG-OBI to purchase one additional treatment of doxorubicin/cyclophosphamide chemotherapy. Methods: Simulation modeling from the US payer perspective utilizing:average selling price (ASP) derived from CMS Q1 2020 reimbursement limits for PEG/PEG-OBI, pegfilgrastim-cbqv, doxorubicin and cyclophosphamide;between one and six cycles of prophylaxis in a panel of 20,000 cancer patients at risk for CIN/FN; and conversion rates from PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv ranging from 10% to 100%. Results: Using current ASP, cost-savings of biosimilar pegfilgrastim-cbqv over PEG/PEG-OBI in a panel of 20,000 breast cancer patients range from $445,163 (for one cycle of prophylaxis at 10% conversion) to $26,709,788 (6 cycles at 100% conversion). In a single cycle of chemotherapy, these savings translate into expanded access to doxorubicin/cyclophosphamide ranging from 1,286 cycles at 10% conversion from PEG/PEG-OBI to 12,861 cycles at 100% conversion. The savings over six cycles could provide between 7,717 additional cycles of doxorubicin/cyclophosphamide (at 10% conversion) to 77,166 cycles (at 100% conversion). The NNC from PEG/PEG-OBI to purchase one additional cycle of doxorubicin/cyclophosphamide is 2. Conclusions: These models demonstrate that CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv can generate significant cost savings for supportive cancer care. Further, these savings could be reallocated to provide access to curative anti-neoplastic treatment on a budget-neutral basis, thus enhancing the value of cancer care to both payers and patients.
Cost and efficacy of low-dose pembrolizumab in the treatment of non-small cell lung cancer patients in Asia.
Authors: Low Jia Li , Sooi Kenneth , Huang Yiqing , Chan Gloria HJ , Ang Yvonne , Chong Wan Qin , Tan Hon Lyn , Ngoi Natalie , Choo Joan , Lee Matilda , Muthu Vaishnavi , Asokumaran Yugarajah , Walsh Robert John , Wong Rachel Su Jen , Chan Zhi Yao , Soo Ross A. , Sundar Raghav , Yong Wei-Peng 
Published: May 2020

e19385 Background: Pembrolizumab has dramatically improved the survival of patients with non-small cell lung cancer (NSCLC) and is considered the standard of care for first line treatment of NSCLC who do not harbour oncogenic drivers. The fixed dose of 200mg was approved by the US Food and Drug Administration. The dose of 200mg was based on pharmacokinetic analysis. Studies have demonstrated equivalent efficacy with weight-based dosing 2mg/kg. An average Asian weighs 50-60kg. We aimed to look at the efficacy of pembrolizumab at a low fixed dose compared to the standard dosing. Methods: A review of all consecutive patients receiving pembrolizumab for advanced NSCLC from January 2016 to December 2019 in a large, high-volume academic medical centre, the National University Hospital, Singapore was conducted. Data fields collected include patient’s demographics, treatment doses and clinical characteristics. Time on treatment and overall survival were analysed using the Kaplan Meier method. Results: In total, 92 ECOG 0-2 patients with advanced NSCLC were treated with pembrolizumab. Median age was 69 years (Range, 29-92). Most were males (76%) and Chinese race (68%). Of the 92 patients, 46 (50%) and 46 (50%) received 100mg (Pem100) and 200mg (Pem200) of pembrolizumab respectively. Pembrolizumab was prescribed as first line in 73 (79%) and second line in 19 patients (21%). The average dose of pembrolizumab received in the low dose group was 1.87mg/kg (Range, 1.24mg/kg – 2.70mg/kg). 88 patients were included in the survival analysis. 4 were excluded due to the presence of an oncogenic driver. Patients were followed up for a median of 13.2 months. There was no difference in progression free survival between Pem100 and Pem200 for first-line single agent and when combined with chemotherapy (PFS: NR versus 5.3months, HR 2.17, 95% CI 0.76-6.16, p = 0.15 and NR vs 16.9 months, HR 2.89, 95% CI 0.35-25.16, p = 0.33 respectively). For patients who received pembrolizumab in the first line setting, the response rate was 56% vs 20% (p = 0.07), 67% vs 52% (p = 0.69) for Pem100 and Pem200 as a single agent and when combined with chemotherapy respectively. The median number of cycles received was 8.9 (Range, 1-60 cycles), translating to estimated cost savings of SGD 45 395 (~ USD 32 664) per patient who received Pem100. Conclusions: A lower fixed dose of pembrolizumab at 100mg showed no difference in progression free survival and response rate in an Asian cohort with significant cost savings. A further randomised controlled trial in an Asian population should be carried out.