bluuebunny/crossref_metadata_2025 huggingface dataset:
Profile of cancer patients admitted in a emergency room of a charity hospital in Southeast Brazil.
Authors: Aleixo Sabina B. , Meneguelli Daiana , Molina Nicolly Del Carmen Parra , Pulido Jose Zago
Published: May 2020

e19307

Background: Given the increase in cancer cases worlwide, there has been a high demand for urgent and emergency care by oncologic patients. Despite the high demand there is still a lack of studies on the oncological population in the context of urgency and emergency especially in the developing countries like Brazil. Methods: Retrospective longitudinal study. Sample consisted of the medical records of cancer patients who were admitted to the service, selected according to the inclusion and exclusion criteria, covering a period of one year. The variables evaluated were: age, gender, comorbidities, primary site, metastasis, intrahospital transfer, discharge type, days of hospitalization, hospitalizations within one year. Results: Identified 388 patients with a total of 1235 consults among them.; 237 (60.9%) were male, with mean age of 66.5 years old; 151 (39.1%) were female with a mean age of 59.77 years old. The most frequent primary site of cancer was intestine/colon/rectum (14.9%), followed up by hematological cancer (13.8%), and breast cancer (11.5%). Metastasis was identified in 93 patients, with liver as the most commom site of metastasis. The most commom complaints were pain(37.3%), dyspnoea (9.7%), weakness (7.6%), and nausea/vomiting (7.6%). Most patients were not transfered for other hospital units, 20.6% of the consults resulted in transfer to the Oncology Nursery, and 2.7% of the consults resulted in transfer to the Intensive Care Unit. Regarding to type of discharge, 85% of the admissions resulted in discharge, 10% resulted in death, 0.89% resulted on evasion, and the rest of the patients were still hospitalized at the end of this research. The minimum of consults in one year was 1, while one patient visited the ER 35 times. Conclusions: We found that the oncology population seek frequently for ER consults, with pain as the most common complaint.The most common cancer on our service was intestine, followed up by hematological cancer and breast cancer. The majority of the consults resulted in discharge. We suggest more research approaching different ways to assess, classify and to treat oncologic pain, considering that most patients have follow up with their attending physician and yet they seek ER to treat this symptom. Also,we suggest that the population must be clarified and educated about the real role of the ER service to avoid excessive consults.
Utilization of next-generation sequencing and associated systemic therapy initiation in metastatic prostate cancer.
Authors: Yang Daniel X. , Leapman Michael , Gross Cary Philip , Yu James B.
Published: May 2020

e19308

Background: There is emerging evidence for using clinical genomic classifiers for prognostication and to guide treatment choice in metastatic prostate cancer (mPC). While clinical-grade next generation sequencing (NGS) tests are increasingly available, how NGS has impacted systemic therapy selection for mPC is unclear. Methods: We performed retrospective observational study using the nationwide US Flatiron Health EHR-derived de-identified database. We identified patients with mPC diagnosed between January 1, 2013 and September 31, 2019. Receipt of NGS testing was chart-confirmed. “Short-interval” systemic therapy initiation in association with NGS testing was defined as line of therapy start within 30 days of documented NGS test result date. Results: A total 11548 mPC patients were included in our cohort, of which 1034 patients (8.9%) had documented NGS after metastatic diagnosis. There were 1210 documented NGS tests total, with 146 (14.1%) patients documented as undergoing NGS testing on more than one occasion. Median time from metastatic diagnosis to initial NGS test results was 560 days (IQR 194 to 1016 days). NGS test documentation increased from 7.1% of cases diagnosed in 2013 to 12.1% of cases diagnosed in 2017 (p < 0.001). A new line of systemic therapy was initiated within 30 days for 207 NGS test results (17.1%). Although the percent of NGS tests associated with short-interval initiation of a new line of therapy increased from 11.1% in 2013-2014 to 16.5% in 2018-2019, the difference was not statistically significant (p = 0.540). The most common systemic therapies initiated within 30 days after NGS testing were docetaxel (18.8%), cabazitaxel (16.8%), and abiraterone (15.4%). Conclusions: While there has been an increase in documented NGS tests in mPC, rates of short-interval systemic therapy initiation after NGS did not change significantly from 2013-2019. Further study is needed as to whether this will increase in years to come, as well as potential improvements in clinical outcomes due to therapy change.
Use of prophylactic cranial irradiation in patients with extensive-stage small cell lung cancer receiving immunotherapy.
Authors: Yang Daniel X. , Jairam Vikram , Park Henry S. , Decker Roy H. , Chiang Anne C. , Gross Cary Philip , Yu James B.
Published: May 2020

e19309

Background: Prophylactic cranial irradiation (PCI) use is controversial in extensive-stage small cell lung cancer (ES-SCLC). In addition to lack of survival benefit of PCI compared to close MRI surveillance in a 2017 published trial, the role of PCI is being further challenged in the modern immune-oncology (IO) era. The IMpower133 trial reporting a survival benefit to atezolizumab for ES-SCLC published in 2018 did not require PCI use. Contemporary practice patterns of PCI in relation to immunotherapy are unknown. Methods: We performed a retrospective cohort analysis of patients with ES-SCLC diagnosed between January 1, 2013 to September 31, 2019 from the nationwide Flatiron Health electronic health record-derived de-identified database. First-line chemotherapy (Chemo) was defined as Chemo given alone, while first-line IO therapy was IO alone or combined with chemotherapy as initial systemic therapy. Results: The cohort included 3047 ES-SCLC patients who received first-line Chemo, and 324 patients who received first-line IO. For first-line IO patients, 268 (82.7%) received first-line atezolizumab. The use of first-line IO increased from 1.2% of patients diagnosed in 2013 to 11.3% of patients diagnosed in 2018 (p < 0.001), and 54.5% of patients diagnosed in 2019 (p < 0.001). Overall documented PCI for patients receiving either first-line IO or first-line Chemo decreased from 14.7% in 2013 to 7.0% in 2018-2019 (p < 0.001). For first-line IO patients, 23 (7.1%) had documented PCI over our study period, with 5.3% of patients diagnosed in 2018-2019 having received PCI. In contrast, for first-line Chemo patients, 428 (14.0%) received PCI over our study period, and PCI use significantly decreased from 14.8% in 2013 to 7.9% in 2018-2019 (p = 0.001). In 2018-2019, use of PCI was not significantly different between patients receiving first-line IO compared to first-line Chemo (5.3% vs 7.9%, p = 0.163). Conclusions: The use of first-line IO has significantly increased in ES-SCLC. Overall PCI rates for ES-SCLC patients decreased significantly over the study period, although documented PCI use rates do not differ between patients receiving upfront IO or Chemo in 2018-2019. Further investigation is warranted regarding effectiveness of PCI in the modern IO era.
Trends in immunotherapy use in patients with advanced non-small cell lung cancer (aNSCLC) patients: Analysis of real-world data.
Authors: Kushi Lawrence H. , Lasiter Laura , Belli Andrew J. , Boyd Marley , Bruinooge Suanna S. , Christian Jennifer , Garrett-Mayer Elizabeth , Hansen Eric , Honnold Rebecca , Pe Benito Ruth , Natanzon Yanina , Sakoda Lori , Rivera Donna R. R , Rhodes Whitney , Robert Nicholas J. , Sharon Elad , Sweetnam Connor , Wagner Joseph , Walker Mark S. , Allen Jeff
Published: May 2020

e19311

Background: Leveraging data from a collaboration with 9 data partners, Friends of Cancer Research convened the Real-world Evidence Pilot 2.0, to examine trends and real world (rw) data endpoints in immunotherapy (IO) use for the front line treatment of aNSCLC. Methods: This study leveraged parallel analyses of rw data elements across heterogenous data sources (EHR, administrative claims, and registry) to: a) describe trends in uptake and use of novel IO frontline therapy after advanced diagnosis in NSCLC patients treated in usual care settings and b) examine associations between treatment and rw outcomes at one-year follow-up. The proportion of patients treated on each regimen (IO single agent, chemo, or IO + chemo) from 2011 through 2017 were calculated. Analysis included proportion of patients across treatment regimens stratified by year to describe post approval uptake of IO. Kaplan-Meier survival estimates were reported to adjust for follow-up time and stratified by PD-L1 status and stage. Results: Seven datasets identified a range of 999 to 4617 patients per dataset for this analysis. Across datasets, 2508, 3446, and 4176 patients initiated treatment in 2015, 2016, and 2017, respectively. No patients received IO or IO + chemo regimens prior to 2015. Initial approvals for IO use in aNSCLC occurred in October 2015 and for first line in metastatic NSCLC in October 2016. When examining survival at 1 year, overall, OS in PD-(L)1 + patients appeared longer than those with a PD-(L)1 - status. Conclusions: RWE analyses may reveal important trends in clinical cancer patient care including patterns of off-label use. The heterogeneity in the timing of IO uptake across datasets ranged from immediately after approval to ~12 months post-approval. [Table: see text]
Uptake of first-line immune checkpoint inhibitors among medically frail patients with advanced solid malignancies.
Authors: Parikh Ravi Bharat , Cohen Roger B. , Min Eun Jeong , Wileyto E. Paul , Riaz Fauzia , Gross Cary Philip , Long Qi , Mamtani Ronac
Published: May 2020

e19316

Background: There are concerns about use of immune checkpoint inhibitor (ICI) therapy in medically frail patients, for whom ICIs do not have a proven survival or quality-of-life benefit. We compared uptake of first-line ICI treatment in routine practice between frail and non-frail patients with advanced solid malignancies. Methods: This retrospective cohort study used data from the Flatiron Health electronic health record-derived database. We included patients who started first-line systemic therapy from 2014 through 2018 for stage IV non-small cell lung cancer (NSCLC) without a targetable mutation, urothelial cell carcinoma (UCC), renal cell carcinoma (RCC), or hepatocellular carcinoma (HCC). We identified medically frail patients using literature-based criteria: Eastern Cooperative Oncology Group performance status (ECOG) ≥ 2, Elixhauser comorbidity index ≥ 3, or grade ≥3 liver or renal dysfunction as defined by NCI CTCAE v5. We used multivariable logistic regressions to examine associations between frailty and the probability of first-line use of an ICI-containing regimen (monotherapy or combination therapy), adjusted for age, insurance type, academic vs. community practice setting, type of cancer, and year of treatment. Results: Of 23,972 patients in the cohort, 17,122 (71.4%) were white, 10,237 (42.7%) were female, 9,666 (40.3%) were commercially-insured, and 13,144 (54.8%) met criteria for frailty. ICI use steadily increased over time in frail patients: among frail patients diagnosed in the last quarter of 2018, ICI-containing regimens represented 55% of first-line therapy starts in NSCLC; 35% in UCC; 55% in RCC; and 23% in HCC. Frail patients had a slightly higher likelihood of ICI use compared to non-frail patients (adjusted odds ratio [aOR] 1.12, 95% CI 1.04-1.20, p=0.002). This was primarily driven by greater use in patients with high comorbidity (aOR 1.15, 95% CI 1.08-1.23, p<0.001) (Table). Associations were consistent when examining first-line ICI monotherapy use only. Conclusions: First-line ICI use is common and increasing among frail patients with advanced solid malignancies. Prospective evidence is needed to assess the benefit (or lack thereof) of ICI use in medically frail patients. [Table: see text]
MET status and treatment outcomes in papillary renal cell carcinoma (PRCC): Pooled analysis of historical data.
Authors: Albiges Laurence , Heng Daniel Yick Chin , Lee Jae-Lyun , Walker Stephen , Mellemgaard Anders , Ottesen Lone , Frigault Melanie M. , L'Hernault Anne , Wessen Jonathan , Choueiri Toni K. , Cancel Mathilde , Signoretti Sabina
Published: May 2020

e19321

Background: PRCC accounts for 10–15% of RCCs, but there are limited biomarker-based data to inform targeted treatment. Treatments for patients (pts) with advanced/metastatic PRCC include those approved for clear cell RCC such as sunitinib or everolimus, however their activity in PRCC can be limited. A subset of PRCCs are MET-driven, and it has been suggested that this may be a negative prognostic factor, although the role of MET activation in advanced/metastatic disease is unclear. We explored the prevalance of MET status in pts with advanced/metastatic PRCC treated with targeted therapies and impact on clinical outcomes. Methods: This large, international, retrospective, observational study included pts with previously treated, locally advanced/metastatic PRCC. MET status was determined retrospectively by NGS of archival tissue. MET-driven disease was defined as MET and/or HGF amplification, chromosome 7 gain (requiring > 30% tumor content) and/or MET kinase domain mutations. Study objectives included progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS) by MET status. Results: 305/308 pts (International Metastatic RCC Database Consortium, n = 72; The Asan Genito-Urinary Cancer Center, n = 40; Groupe Français d’Etude des Tumeurs Uro-Génitales, n = 196) received first-line (1L) treatment; sunitinib was most common (68%). 214 (69%) pts received 2L therapy; everolimus was most common (20%). Of 179 pts with valid NGS results, 38%, 49% and 13% had MET-driven, MET-independent (ind) tumors and chromosome 7 ploidy unevaluable, respectively. Baseline demographics were mostly balanced among groups. In sunitinib-treated pts, PFS and TTF were numerically longer in pts with MET-driven tumors vs pts with MET-ind tumors, but OS was similar (Table). In everolimus-treated pts, PFS and TTF were similar for both MET groups; however the sample size was small. Conclusions: MET alterations are frequent in advanced/metastatic PRCC and have potential to impact PFS and TTF, although our results show limited effect on OS. These data show that MET-driven tumours may not predict for poorer outcome vs MET-ind tumours and there is a need for suitable therapies for MET-driven PRCC. [Table: see text]
Use and outcomes in men with metastatic castration-sensitive prostate cancer (mCSPC) treated with docetaxel in addition to androgen deprivation therapy (ADT): Analysis of real-world data in the United States (US).
Authors: Agarwal Neeraj , Mundle Suneel , Dearden Lindsay , Potluri Ravi C. , Nair Sandhya , Mehra Maneesha
Published: May 2020

e19322

Background: mCSPC patients treated with docetaxel + androgen deprivation therapy (D+ADT) demonstrate increased overall survival (OS)1,2. However, limited real-world outcome data is available for such patients. This study assesses the real-world use and outcomes with D+ADT in mCSPC in the US. Methods: Adult (≥18 years old) men with mCSPC (defined as men with metastasis at index diagnosis of prostate cancer [de novo] or those who progressed to mCSPC after prior diagnosis of localized disease) were retrospectively identified from the Optum (2007–2018) and SEER Medicare (2007–2016) databases. Men diagnosed with mCSPC in or after 2014 with exposure to docetaxel and no brain metastasis were included for analysis. Patients were characterized based on age; baseline prostate specific antigen (PSA) level; administration of ADT; prior radiotherapy (RT); prior radical prostatectomy (RP); presence of visceral disease, bone or bone + visceral metastases; and treatment duration of docetaxel. OS and time to metastatic castration-resistant prostate cancer (mCRPC) were measured. Results: Among 4959 men identified with mCSPC during or after 2014, 192 (3.8%) received D+ADT ± Bicalutamide as first line systemic therapy. Baseline characteristics are presented in the Table below. Mean ± SD duration of docetaxel exposure was 115 ± 84.2 days (median 118 days). Median OS among these men was 30.5 (28.1, 36.7) months and median time to mCRPC was 18.3 (14.5, 24.6) months. Only 9% of men received docetaxel for ≥6 cycles (180 days); median OS in these men was NR (19.1- NR) with 74% surviving at 2 years compared to 65% surviving at 2 years in those with docetaxel duration <6 cycles. Conclusions: Use of docetaxel in the real-world mCSPC patient population in the US is limited. Majority of men received less than the recommended dose of 6 cycles. OS with D+ADT in real-world patients with mCSPC appears to be lower than the OS reported in published trials. References:1) Sweeney CJ, et al. N Engl J Med. 2015;373:737–46. 2) James ND, et al. Lancet. 2016;387:1163–77. Funding: Janssen Research & Development, LLC. [Table: see text]
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.
Resource utilization and cost efficacy analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (DD-MVAC) versus gemcitabine-cisplatin (GC) as neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC).
Authors: Montazeri Kamaneh , Dranitsaris George , Curran Catherine , Thomas Jonathan David , Ingham Matthew D. , Preston Mark A. , Steele Graeme S. , Kilbridge Kerry L. , Wei Xiao X. , McGregor Bradley Alexander , Mossanen Matthew , Sonpavde Guru
Published: May 2020

e19390

Background: DD-MVAC and GC are commonly used NAC regimens for MIBC. While efficacy across studies appears similar, resource utilization (RU) burden and cost efficacy have not been compared. Methods: We assessed RU and cost effectiveness of NAC with GC vs DD-MVAC among MIBC patients (pts) treated at Dana-Farber. Data on chemotherapy administered, supportive medications, relevant procedures, hospitalizations, clinic, infusion, and emergency room (ER) visits were collected retrospectively. Unit costs for each RU component were sought from the Centers for Medicare and Medicaid Website as well as relevant published sources. Utilization was compared between MVAC and GC using multivariate quantile regression (QR) analysis. Results: 147 pts were included; 51 received DD-MVAC and 86 GC. Baseline characteristics were similar, except lower mean age (59 vs 67 years, p < 0.001) and higher proportion of ECOG-PS = 0 (96.1% vs 60.5%, p < 0.001) for DD-MVAC. The mean cumulative cisplatin dosage was similar (DD-MVAC = 284 mg/m2, GC = 257 mg/m3). More DD-MVAC pts required G-CSF analogues (100% vs 32.6%, p < 0.001), central line placement (28.6% vs 11.8%, p = 0.017), and ER visits (35% vs 18%, p = 0.048). Infusion visits (12 vs 8/pt) and cardiac imaging (0.98 vs 0.58/pt, p < 0.001) were higher for DD-MVAC, whereas GC pts required more frequent clinic visits (mean of 9 vs 5/pt), chemotherapy cycle delays (30.2% vs 9.8%, p = 0.008) and hospitalization days (mean of 0.88 vs 0.49/pt). After adjusting for PS, the mean total cost/pt was higher for DD-MVAC ($17360 vs $12112, p < 0.001). Age was not statistically significant in the QR model (p = 0.628). Conclusions: DD-MVAC and GC exhibit different RU characteristics as NAC for MIBC. Although excess RU did not clearly favor one regimen, adjustment for PS indicated significant decrease in healthcare costs by approximately 30% using GC compared to DD-MVAC. Given that similar overall delivery of cumulative cisplatin dosage was feasible with both regimens, the values and costs affixed to different resources may impact the selection of DD-MVAC vs GC. Limitations were retrospective design and costs being specific to the US.
Predictors of increased episode expenditure and exceeding target price under the oncology care model.
Authors: Park Seojin , Waters Dexter , Thomas Ryan , Song Andrew Jehyun , Walsh Karen , Csik Valerie Pracilio , Leader Amy , Maio Vittorio
Published: May 2020

e19403

Background: The Oncology Care Model (OCM) incentivizes participants to keep episode expenditure below target price; however, little is known about the adequacy of adjustments in target price calculation. This study investigates predictors of increased expenditures and explores how these predictors are associated with exceeding target price for hematologic and solid malignancies. Methods: Non-decedent OCM episodes, categorized as hematologic malignancies (HMs) or solid malignancies (SMs), from 7/1/2016 - 7/1/2018 attributed to our institute were analyzed. Multiple linear regression was used to identify factors associated with increased episode expenditure. Multiple logistic regression was used to evaluate whether such factors increased likelihood of expenditure exceeding target price. Results: Of 1,975 episodes, 499 (25.3%) were HMs and 1,476 (74.7%) were SMs. 54.3% of HMs and 35.2% of SMs had episode expenditure exceeding target price. In HMs, novel therapy use (NT), inpatient admission (INPT), Part B drug use (PB), Part D use (PD), and radiation therapy (XRT) were associated with increased episode expenditure. Of those, INPT and PD increased the likelihood of expenditure exceeding target price. XRT decreased the likelihood of expenditure exceeding target price (Table). In SMs, NT, INPT, emergency department visit, home health aides, durable medical equipment use, PB, PD, XRT, and surgery were associated with increased episode expenditure. Of those, NT, INPT, PB and PD increased the likelihood of expenditure exceeding target price. XRT and receipt of surgery decreased the likelihood of expenditure exceeding target price (Table). Conclusions: INPT and PD significantly increased episode expenditures in both HMs and SMs, leading to expenditures exceeding target prices determined by the OCM benchmark risk-adjustments in both cancer types. NT and PB were significant predictors of increased expenditure and the likelihood of exceeding target price in SMs, but not in HMs. Our findings suggest that there may be opportunities to improve the current model by refining the adjustment for these factors to better reflect real world expenditures. [Table: see text]
Role of epigenetic regulators in single-base substitution patterns in AML.
Authors: Paul Madhuri , Scarpa Frank J , Wolfson Wendy A , Weiss Lawrence , Funari Vincent Anthony , Blocker Forrest
Published: May 2020

e19500

Background: Incidence of Acute Myeloid Leukemia (AML) increases with age, as does Clonal Hematopoiesis of indeterminate Potential (CHiP), wherein specific genes are mutated in healthy individuals. Single Base pair Substitutions (SBS) are associated with aging and AML, most commonly C>T. G>A transitions are found in a similar prevalence in all age groups, although the number of mutations are higher in older age groups and associated with therapy. Determining a pattern of SBS in leukemia that is distinct from aging has been a challenge. Methods: We performed mutational signature analysis on 10,152 mutations in 3,575 unique suspected AML patient bone marrow, peripheral blood, or FFPE tissue samples. Samples were evaluated using an all exon amplicon based 27 gene next generation sequencing panel. The cohort was divided into 5 groups based on age (0-14, 15-39, 40-54, 55-65, and >65 years), as well as into three gene mutation groups 1) TET2 WT (n=7,479 mutations), 2) TET2/DNMT3A WT (n=6,701) and 3) TET2/DNMT3A WT with chromatin regulators WT (ASXL1, ATRX, BCOR, BCORL1, EZH2, PHF6, RAD21, SMC1A, SMC3, STAG2; n=3627 mutations). Results: Predominant SBS were C>T (42.7%) and G>A (59.0%) transitions across all age groups. The percentage of C>T SBS increased with age: 0-14 years cohort (18.0% of cases; 1.5% of mutations) to >65 years cohort (58.8% of cases; 39.6% of mutations). There was no significant change in the prevalence of G>A mutations with age, however, the total number of mutations did increase with age (0-14 0.2% vs >65 39.6%). In each of the gene mutation groups, the number of C>T and G>A total mutations decreases as TET2 MT (42.7% and 59.0%), TET2 WT (27.0% and 45.1%), TET2/DNMT3A WT (20.8% and 34.3%), and TET2/DNMT3A WT with WT chromatin regulators (10.1% and 25.5%). Conclusions: In this study, both the prevalence and number of mutations in AML patients increases with age for C>T transitions, but for G>A transitions only the number of mutations increases with age, consistent with previously reported studies. In this data set, by removing mutations in TET2, TET2 and DNMT3A, TET2 and DNMT3A with genes that regulate chromatin accessibility, the number of C>T and G>A transitions decreases in order of effect, with the chromatin modifiers having the largest effect. The effect of removing these mutations suggests a mechanism driving leukemogenesis whereby DNMT3A methylates cytosine, TET2 deaminates this methylated cytosine, and finally chromatin modifiers regulate accessibility to these methylation sites, thereby modulating downstream oncologic pathways.