bluuebunny/crossref_metadata_2025 huggingface dataset:
Laboratory and clinical data integration: Toward an evidence development framework.
Authors: Anderson Lori , Goede Patricia , Koskimaki Jacob , Kakamada Sirisha , Rubinstein Wendy S.
Published: May 2019

e18318

Background: Decision making in precision oncology relies on the timeliness of diagnostic testing. Uncertainty surrounding the clinical utility of laboratory developed molecular and next generation sequencing (NGS) tests (LDTs) has engendered a predominantly manual claims review process. Denials and delays may create hurdles for optimally treating patients, and denials may contribute to financial toxicity. ASCO’s CancerLinQ aggregates clinical data from EHRs of participating oncology practices to improve the quality of care for patients. We hypothesized that standardized clinical data could be used in the short term to appeal denials of NGS LDTs and in the long run, lead to evidence-based coverage decisions. Methods: Using National Provider Index IDs, CancerLinQ participating physicians were cross-walked to ordering physicians of tests offered from 100 U.S. laboratories using XIFIN for billing services in 2018 to evaluate the feasibility of using CancerLinQ clinical data for claims adjudication. We determined the proportion of molecular and NGS tests (based on CPT coding) initially denied and the proportion of successful appeals through a manual submission process for clinical documentation (not including CancerLinQ data). CancerLinQ clinical data were evaluated for key elements necessary for successful appeals. Results: Sixty-five percent of CancerLinQ participating physicians ordered tests from the laboratories identified. Approximately 80% of NGS and 40% of molecular services were initially denied. After appealing with clinical information through the manual process, 55% of denials were successfully overturned. Key clinical data provided manually could be automatically extracted from CancerLinQ at high rates, such as ICD-9/ICD-10 cancer diagnosis (100% of 1,082,606 patients), Stage Group (47.6 %), and treatment plan (35.9%). Metastatic disease status is available through M1-stage (23.2% of total M-Stage), AJCC Stage IV (29.0% of total AJCC Stage) and Metastatic diagnosis codes (17.2%). Conclusions: CancerLinQ contains key data elements necessary for successful appeals and can streamline the claims adjudication process, ultimately helping to build the evidence base for coverage decisions.
Association of patient characteristics with real-world ROS1 NSCLC testing patterns among community practices in the United States.
Authors: Wong William Bruce , Wu Ning , Gupta Ravindra , Mansfield Aaron Scott
Published: May 2019

e18321

Background: Despite the availability of targeted therapy for ROS1 NSCLC since 2016, there is limited information on real-world ROS1 testing practices to identify patients potentially eligible for targeted treatment among community practices. The objective of this study was to characterize ROS1 testing rates and identify potential barriers to ROS1 testing. Methods: The Flatiron Health EHR-derived database was used to identify patients diagnosed with advanced NSCLC between 7/1/2016 - 7/30/2018 and received systemic treatment in a community practice setting. Descriptive statistics were used to summarize the population, biomarker testing rates and timing of testing. Logistic and multinomial regressions including patient demographics and clinical characteristics were used to identify factors associated with the following outcomes: ROS1 testing, testing for biomarkers other than ROS1 (PDL1, ALK, EGFR) , longer times from advanced diagnosis (adv. dx) to ROS1 test results and initiation of therapy prior to ROS1 testing. Results: Of 9,275 eligible patients, ROS1 testing rates in squamous (SQ) and non-squamous histologies increased over the study period (30% to 52%, 62% to 75% respectively). Older age, males, poorer performance status, SQ histology, history of smoking and recurrent disease (RD) patients were significantly less likely to be tested. Among patients not tested for ROS1, 62% were tested for other biomarkers including > 50% of non-squamous patients tested for PDL1, EGFR or ALK and 51% of squamous patients tested for PDL1. The median time from adv. dx to test result was 24 days, with patient characteristics (i.e. Hispanic ethnicity, history of smoking) as well as test type predicting longer times to test results ( > 41 days vs. < 24 days after adv. dx). Patients who had a delay in test results were more likely to receive other therapy prior to availability of their ROS1 test results (25+ days vs. < 24 days OR [95% CI]: 9.18 [7.87, 10.70]). Conclusions: In real-world practice, patient characteristics were associated with ROS1 testing and testing delays which may result in some patient subgroups being less likely to be identified for potential targeted therapy.
The practical ethics of medication shortages: Understanding patient preferences for allocation, decision making, and disclosure through narrative inquiry.
Authors: Hantel Andrew , Hlubocky Fay J. , Quinn Michael , Lee Sang Mee , Siegler Mark , Daugherty Christopher
Published: May 2019

e18323

Background: Hospital medication shortages (HMS) are pervasive throughout the U.S. healthcare system. Current management mechanisms are heterogeneous but routinely include the use of alternatives and the rationing of medications between patients. Little is known about oncology patient preferences for decision-makers, ethical allocation systems, or thresholds for disclosure during HMS. Methods: Oncology patients previously hospitalized for inpatient care within the last 24 months underwent qualitative interviews supplemented with validated instruments measuring: trust (Trust in Oncologist Scale), therapeutic alliance (Human Connection Scale), and shared decision-making (Shared Decision-Making Questionnaire). Qualitative data underwent Framework Analysis for thematic identification. Results: To date, 16 patients have been interviewed: median age 61y (31-77); 44% female; 56% married; 56% > college education; median number of treatment regimens 2 (1-6), days in hospital 18 (3-66), number of hospitalizations 2(1-8). All patients (100%) reported extremely high levels of trust, therapeutic alliance, and shared decision-making with their oncologist. Two patients (13%) reported personal experiences with HMS, 43% reported knowledge of HMS within the U.S., and no patients reported knowledge of local hospital HMS. Framework Analysis revealed that virtually all patients preferred that their oncologist act as the primary decision-maker during allocation/rationing and favored pharmacist and ethicist involvement. Most patients preferred allocation systems that prioritized efficacy, age, and degree of illness. No patients desired the use of a lottery or reciprocity-based decisions. Virtually all patients favored disclosure of shortages if alternatives were used, independent of the level of difference in efficacy/toxicity, and in the case of both chemotherapeutics and supportive medications. Conclusions: Despite ubiquitous HMS in oncology, patients are generally unaware of local HMS and prefer: multi-disciplinary decision-makers during HMS allocation, prioritized allocation schemes, and more frequent HMS disclosure than presently occurs. Study recruitment is ongoing.
Development and feasibility of virtual molecular tumor board.
Authors: Verma Amit , Kaur Jatinder , Gupta Amit , Aggarwal Aakriti , Kushwaha Arpana , Julka Pramod Kumar , Mehta Prashant , Singh Randeep , Lal Vandana
Published: May 2019

e18334

Background: Practicing precision oncology is challenging due to the complex molecular interpretation and its implications in deciding pertinent treatment options. This is addressed by institutional Molecular Tumor Board (MTB) which is presided by all oncology sub-specialists including molecular biologist and bioinformatician, doing a meticulous job in untwining the intricacies but fail to obtain experiences across institutes. Further, meeting of all MTB members is neither always feasible nor accessible for the community oncologists. We hereby offer a virtual formation of MTB that is easily accessible and remotely attended by various experts across institutes, giving their opinion objectively at their ease that can be documented and archived. Methods: Virtual MTB (vMTB), a mobile cloud-based application was developed for both android and iOS platforms. The vMTB process involves submission and review of cases, whereby assigned members can opine blindly and rate different treatment options. Followed by averaging of rating score and then a final recommendation generated by the vMTB case-convener within 7 days, based on clinical context. A pilot study (2 months duration) was carried out where clinical cases bearing molecular information were invited from various oncology centers across India. Results: 21 cases were submitted (19 relapsed refractory, 3 treatment naïve) that included Breast (6), Lung (5), Leukemia/Lymphoma (3), Gall bladder (2), Uterine (2), Urinary bladder (1), GBM (1) and Sarcoma (1) cancers. The molecular query was based on 18 somatic (8 FoundationOne & 10 Others) and 3 germline testing. Cases assigned to vMTB members (~7 members/case) had ~ 6 treatment options/case with a response turn-around time ~4 days. Therapeutic final recommendation(s) were given for all cases with 95% concordance among the members; 6 cases where multiple options were advised, discordance rate was 14%. Additional molecular diagnostic workup was advised in 3 cases. vMTB recommendations including 10 off label treatment options were accepted by majority of the submitting physicians (82%). Clinical benefit was observed in 5 (24%) cases within the stipulated analysis duration. Conclusions: vMTB is a user-friendly, feasible, acceptable mobile solution alternate to MTB for objectively generating clinically meaningful consensus document for complex molecular clinical case scenarios, where guidelines are limited. To best of our knowledge, this is a first smart mobile solution connecting various oncology experts and have an immediate utility for the practicing community oncologists globally.
Crowdfunding for lung cancer costs.
Authors: Nguyen Ryan , Hanna Nasser H. , Vater Laura
Published: May 2019

e18340

Background: Online crowdfunding, where individuals create campaigns to solicit donations, has grown as an avenue to combat the financial toxicities of cancer. The online platform GoFundMe hosts more than 80% of the global market for crowdfunding and has raised over US $5 billion from more than 50 million donors. While medical expenses are the leading cause of crowdfunding campaigns, limited research is available on the use of crowdfunding for cancer costs. Further, no studies have evaluated the use of crowdfunding for patients with lung cancer. Methods: In January 2019, we reviewed the first 200 consecutive campaigns that resulted for “lung cancer” on GoFundMe. Campaigns were included for analysis if their description stated funds were to be used for medical costs for a patient with lung cancer in the United States. Standardized data was collected from each campaign. Descriptive statistics were used to aggregate results. Multivariable linear regression analysis were performed to examine predictors of funds raised, adjusting for campaign duration. Results: The 157 included campaigns raised a total of US $1.2 million (mean $8,364) from 11,919 donors (median 53). Compared to a similar 2018 study, our study showed lung cancer campaigns raised less than breast cancer (mean $16,026) but more than prostate cancer (mean $1,449) campaigns. Nine campaigns that were seeking funds for alternative treatment raised a total of $119,660 (mean $13,296). Narratives of financial need that were significantly associated with greater funds raised were family financial need (+$7,416), medical costs not covered by insurance (+$7,369), and the campaign stating the patient was a never-smoker (+$8,162) (all P values < 0.05). Conclusions: Lung cancer has received less research funding relative to other cancer types and our study suggests a similar disparity with crowdfunding for medical costs. The “blame-the-victim” attitude that contributes to this funding disparity also exists within lung cancer crowdfunding as evidenced by the significantly greater amount of funds raised for campaigns that explicitly stated the patient was a non-smoker. Efforts to study crowdfunding for cancer costs should address the ethical implications of exacerbating funding disparities and funding for alternative treatments.
Understanding differences in total cancer care cost by service site.
Authors: Fields Karen K. , Burkett Jason M , Terrano Cindy , Dukes Floyd , Gorantla Bharat , Salganicoff Marcos , Rao Bharat
Published: May 2019

e18345

Background: Oncology providers are under mounting pressure to deliver high quality and increasingly complex cancer treatment while simultaneously managing the cost pressures coming from payers and patients alike. Developing an effective strategy to compare costs can be an important tool for assessing and improving performance and cost effectiveness from both a clinical and market competitive standpoint. This comparison can be difficult to achieve in practice, especially between different sites of care and across heterogeneous patient populations. Methods: A large commercial claims dataset with reimbursement data for claims incurred between 2014 and 2017 was used to identify lung cancer patients by site of care. We calculated average annual total cost of care (TCC) for a one year period for patients with a new cancer diagnosis following a one year period of no claims for lung cancer. For study purposes, Moffitt Cancer Center (MCC) was compared to two other peer groups: Large Hospital Systems (LHS) and small hospitals and community-based oncology practices (CBOP). Patients were assigned to each peer group when a majority of claims ( > 70%) were attributed to one of the peer groups. We analyzed overall average annual TCC for all patients and then created a sub-cohort of patients who received surgery within the study period to define early stage patients based on known standard patterns of care for newly diagnosed lung cancer. Results: There were 1249 new lung cancer patients in the study across all three peer groups with an average annual TCC of $134K per patient (range: $110K to $149K). When considering the sub-cohort of early stage patients (n = 396), MCC’s average annual TCC was $124K per patient which was significantly lower than LHS ($152K; p < 0.0499) and CBOP ($167K; p < 0.01). Conclusions: Although claims data generally contain only limited clinical information such as procedures, supplies and diagnosis, this limitation can be address by incorporating known standard of care patterns for cancer treatment to create comparable groups. Using this approach, national claims sets can be leveraged as the basis of a powerful analysis tool for understanding the Total Cost of Cancer care across institutional boundaries while still achieving meaningful comparability of the analyzed patient population.
Real-world demographic and clinical characteristics of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in the United States (US).
Authors: Yang Xiaoqin , Laliberté François , Germain Guillaume , Raut Monika Kumar , Duh Mei Sheng , Sen Shuvayu , Lejeune Dominique , Cavanaugh Cristi , Desai Kaushal , Armand Phillippe
Published: May 2019

e18347

Background: DLBCL, the most common type of non-Hodgkin lymphoma in the US, is associated with significant morbidity and mortality. In October 2015, DLBCL was differentiated from other related lymphoma entities with the advent of ICD-10-CM DLBCL-specific codes. With limited real-world data on patients (pts) with DLBCL in the modern treatment era, this study was conducted to characterize these pts. Methods: A retrospective study was conducted using the Optum Clinformatics Data Mart database (01/2013–03/2018). Pts ≥ 18 years of age with ≥ 1 hospitalization or ≥ 2 outpatient visits with an ICD-10-CM diagnosis code for DLBCL (or an antecedent diagnosis of other lymphoma, which may have been assigned before confirmation of DLBCL) after October 1st, 2015 (index date) and no prior ICD-9-CM code for unspecified DLBCL were identified as incident. Pts with an ICD-9-CM code for unspecified DLBCL before October 2015 (index date) were classified as prevalent. At least 12 months of continuous enrollment pre-index date (baseline period) was required. Pts with ICD-10-CM code for primary mediastinal B-cell lymphoma (PMBCL), baseline diagnoses of other malignancies such as Hodgkin lymphoma and multiple myeloma were excluded. Characteristics, including baseline comorbidities, healthcare resource utilization, and costs were assessed. Results: Among 4,074 DLBCL pts (3,201 incident; 873 prevalent), mean age ± standard deviation (SD) was 71 ± 12 years; 46% were female. Incident and prevalent pts had mean Charlson comorbidity index scores of 2.7 and 2.3, respectively. Most common baseline Elixhauser comorbidities were hypertension (68.4%), diabetes (31.1%), and cardiac arrhythmia (25.3%) in incident pts and hypertension (62.5%), diabetes (28.3%), and chronic pulmonary disease (20.6%) in prevalent pts. Mean ± SD number of baseline hospitalizations was 0.32 ± 0.83 and 0.21 ± 0.49 in incident and prevalent pts, respectively. Total mean ± SD baseline healthcare costs (before diagnosis) were $24,621 ± 45,628 for incident pts and $19,137 ± 29,307 for prevalent pts. Conclusions: This study documents substantial co-morbid and economic burden of incident as well as prevalent pts with DLBCL.
Projecting overall survival data for health-economic models in oncology: Do maturity levels impact uncertainty?
Authors: Roze Stéphane , Bertrand Nicolas , Eberst Lauriane , Borget Isabelle
Published: May 2019

e18350

Background: A lifetime horizon is recommended for health-economic evaluation of anticancer drugs. If overall survival (OS) data is immature, extrapolation of the Kaplan-Meier (KM) curve using distributions is done to obtain long-term data. Depending on OS maturity, the distribution chosen may impact estimation of life expectancy (LE) and of life years gained (LYG) between treatments. This study aimed to estimate the error (on LE and LYG) induced by the choice of extrapolation distributions, for 2 levels of OS maturity (30% and 50%), as compared to LE and LYG at full maturity. Methods: Fifteen phase 3 trials published between 2013 and 2017 containing OS KM curves were selected if maturity > 70% (Full). To test 2 maturity levels, each KM curve was truncated at 30% and 50%. A 3-step process was performed: 1) KM was digitalized, 2) individual patient-data was reproduced using the Guyot algorithm, and 3) 5 parametric survival distributions were fit using the R-Survival package. For each study, the process was done for each treatment arm and each of the 3 maturity levels on the same time horizon, equal to the maximum follow-up of the study. For each curve, the best distribution was chosen by a board of 2 oncologists and 2 health-economists, based on visual inspection, Akaike/Bayesian Information criteria and external validity. Results: Based on the board review of the 90 KM curves, main chosen distributions were Weibull (33%), Log-logistic (32%) and Log-normal (27%). As compared to LE at full maturity, LE was overestimated in 23% and 40% at 30% and 50% maturity, respectively. Mean absolute error was 0.88 at 30% maturity, and decreased to 2.12 at 50% maturity, i.e. estimation was 2.4 times better from 30% to 50% maturity. On average, at 30% maturity versus full, mean percentage of error in LYG was 126.4% and 62.4% at 50% maturity versus full. Conclusions: The use of immature OS data increases the risk of error when projecting long-term LE. Even marginal gains in OS maturity can be translated in more accurate estimations and guide health-economist in developing models.
Cost-effectiveness of programmed cell death protein 1/programmed death-ligand 1 inhibitors (aPD1/aPDL1) varies widely.
Authors: Geisler Benjamin P , Pridham Leesa L. , Monge B. M. Cecilia , Johnson Tali M. , Karnon Jonathan , Sharon Elad
Published: May 2019

e18351

Background: Immunotherapy with aPD1/aPDL1 has been shown to be efficacious for a range of indications. However, cost-effectiveness has only been demonstrated for some. Our goal was to compare incremental costs and effects across Food and Drug Administration (FDA) approved aPD1/aPDL1 using a standardized value framework. Methods: aPD1/aPDL1 randomized controlled trials (RCTs) were obtained from the FDA's 2014-18 approval lists. Restricted mean Overall (OS) and Progression-Free Survival (PFS) were extrapolated to 10 years via best-fitting (Akaike/Bayesian information criterion) parametric function (Kaplan-Meier survival curves digitized via Henley&Hoyle approach). Average wholesale price for experimental and comparator regimens from approval year’s Micromedex Red Book (IBM Watson Health, Cambridge, MA) were applied to either median treatment duration or mean extrapolated PFS, assuming the entire cohort was treated with no dose reductions. For multicenter RCTs with physician’s choice of the comparator, we assumed the regimen most likely used in the U.S. Incremental cost-effectiveness ratios (ICER) were discounted at 3% per annum. Results: Undiscounted OS gains with aPD1/aPDL1 after extrapolation to 10 years ranged from 0.72 to 1.89 LYs as compared to between 0.13 and 0.27 LYs at the end of the RCT. Discounted additional costs for aPD1/aPDL1 ranged from about -$1,700 to $348,312. Crude estimates of the incremental cost per LY gained vary widely, with ICERs for PACIFIC and Impower150 beyond $150,000/LY in both analyses, and additionally Keynote 024 and Checkmate 214 in the analysis that assumed treatment to the end of PFS. Conclusions: Value for money appears to vary widely across indications and comparators, from cost-saving to low-value. Common extrapolation-based analyses of aPD1/aPDL1-based regimens can help elucidate differences in value. The presented analyses are preliminary. Further assessment of extrapolation methods, downstream costs and quality of life effects are required. [Table: see text]
Cost-effectiveness of once weekly carfilzomib 70 mg/m2 plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States.
Authors: Kumar Shaji , Majer Istvan , Panjabi Sumeet , Malacan Jean , Medhekar Rohan , Campioni Marco , Dimopoulos Meletios A.
Published: May 2019

e18356

Background: Carfilzomib plus dexamethasone (Kd) dosed once weekly at 70 mg/m2 (QW Kd70) was recently approved in the US for treating patients with relapsed and refractory multiple myeloma (RRMM). To assess the cost-effectiveness (CE) of QW Kd70 vs twice weekly Kd dosed at 27 mg/m2 (BIW Kd27), data from the phase 3 ARROW trial, which directly compared these regimens in patients with 2-3 prior lines of therapy were used. Methods: A partitioned survival model was developed for the CE analysis. Time to treatment discontinuation, progression-free survival, and overall survival (OS) were estimated from the ARROW trial. Long-term OS was extrapolated using Surveillance Epidemiology and End Results registry data after matching characteristics of patients in the registry and ARROW trial. Direct costs were estimated from a US health care payer perspective. Utilities collected in the ARROW trial using the five-level version of the EuroQol questionnaire (EQ-5D-5L) were applied to estimate the quality-adjusted life years (QALYs). Uncertainty was explored using sensitivity analyses. Two subgroups of patients refractory to lenalidomide or bortezomib were assessed. Main outcomes were mean life-years (LYs), QALYs, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Results: For QW Kd70 and BIW Kd27, the model predicted mean LYs of 4.17 and 3.07 years, QALYs of 2.98 and 2.03 years, and mean total lifetime costs of $444,563 and $373,364, respectively. The incremental LYs gain, QALY gain, and incremental costs of QW Kd70 vs BIW Kd27 were estimated to be 1.10 years, 0.95 year, and $71,199, respectively, resulting in an ICER of $64,595 per LY gained and $75,204 per QALY gained. For patients refractory to lenalidomide and bortezomib, similar results were found with ICERs of $79,988 and $76,793, respectively. Conclusions: In line with ARROW trial results, this CE analysis showed that QW Kd70 is expected to provide considerable additional benefit in terms of LYs and QALYs gained compared with BIW Kd27. In the RRMM setting, QW Kd70 is cost-effective with ICERs below accepted willingness to pay thresholds in US and represents an efficient utilization of the health care budget.
Pharmacy cost in cancer.
Authors: Shah Surbhi , Rubin Nathan
Published: May 2019

e18358

Background: Health care spending in US is highest in the developed world and contributes to up to 1/5 of the GDP. The price escalation is steep and contribution from cancer care is soaring. The cost of medications is deemed to be the leading cause of increased health care spending. In this era of precision medicine, with more effective and better tolerated drugs, patients are using them for longer periods of time, adding to the ever mounting health care spending. Methods: We used a large claims based data set US database MarketScan to explore the economic burden of drug cost in cancer care. Between January 1, 2013 and September 30, 2015 we identified 195,290 enrollees with active cancer. We analyzed the economic burden of medications for overall cancer care by exploring the total cost of care and the pharmacy expenditure by various classes of drugs for these patients. The perspective was that of the health care system as the costs included payments by the insurer and the patient. Results: There were 195,290 active cancer patients in this analysis. Mean age was 61 years, 55% were females. Breast cancer was the most common diagnosis. Mean total cost of care and total drug cost per patient over the study period was $141,415 and $13,579, respectively. The total pharmacy expenditure across all study patients was ~2.5B. Antineoplastic drugs make up the largest portion of the total pharmacy expenditure at 39%. Cost contribution based on drug categories were anti-infective (6%), cardiovascular (6%), central nervous system (including opiates, anti-nausea medications and antidepressants) (7%), blood formulations (including anticoagulants) (8%), hormones (8%) and gastrointestinal drugs (4%) respectively. Conclusions: Based on the real world information from a large insurance claims database, this study quantifies the contribution of various drug classes to the cost of cancer care. Antineoplastic contribute to > 1/3rd of the total pharmacy spending. With increasing trend for immunotherapy and combination therapy drug costs are bound to go up even more steeply. Unless drug prices are regulated, we are looking towards an unsustainable level of growth in the health care spending in cancer care.
Cost effectiveness (CE) of blinatumomab (BLIN) versus inotuzumab ozogamicin (INO) in adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) with no more than one prior salvage therapy (S0/S1) from a United Kingdom health care perspective.
Authors: Delea Thomas E. , Zhang Xinke , Amdahl Jordan , Boyko Diana , Severin Franziska , Campioni Marco , Cong Ze
Published: May 2019

e18359

Background: To estimate Incremental CE Ratio (ICER) of BLIN vs INO in adults with R/R S0/S1 ALL based on matching-adjusted indirect comparison (MAIC) of TOWER and INO-VATE trials from a UK healthcare perspective. Methods: CE was estimated by a partitioned-survival model with outcomes based on published aggregate data from INO-VATE (cutoff: 01/05/2017) and individual patient data from TOWER weighted to match patients in INO-VATE using MAIC. Five analyses were conducted based on alternative approach for the MAIC (anchored through Standard of Care [SOC] vs unanchored), proportional hazard (PH) assumptions, and reference overall survival (OS) distributions. Rates of complete remission and HSCT, utilities, duration of therapy, and use of subsequent therapies also were MAIC adjusted. Due to inconsistent definitions of event-free survival (EFS) between the trials, EFS was assumed to be equal for BLIN and INO complete responders. Costs were estimated from published sources and included those of medicine and administration, key adverse events, HSCT, salvage therapy, and terminal care. Utilities were based on EORTC-8D values derived from EORTC QLQ-C30 assessments in TOWER. A 50-year time horizon was used. Results: In all analyses, BLIN was more costly and more effective than INO. The ICER for BLIN vs INO ranged from £4,014 to £13,371 per QALY. Conclusions: For various approaches for conducting MAIC of BLIN vs INO, BLIN was highly cost effective vs INO in R/R ALL adults with S0/S1 from a UK healthcare perspective. [Table: see text]
Cost effectiveness of updated laboratory monitoring schedule for immunotherapy regimes.
Authors: Ronan Karine , Che Othman Elly Hanis , McKenna Susan , Anderson Cian , Sheehan David , Griffin Margaret , McDermott Ray , Westrup Jennifer
Published: May 2019

e18363

Background: Patients being treated with immunotherapy undergo frequent laboratory testing to monitor for immune-related adverse events (IRAEs) as per National Cancer Control Programme (NCCP) guidelines in Ireland. Current NCCP guidelines advise pre-treatment testing of thyroid function, glucose and cortisol and follow-up TFTs and glucose levels with each cycle of therapy.1,2,3,4. Endocrinopathies occur in approximately 10% of patients on immunotherapy,5 with most occurring in the first three months of treatment.6 Hypophysitis is a relatively common adverse event associated with ipilimumab and with combination treatments, with incidence rates reported at 10-15%.7,8 Methods: On review of our own cohort and recent publications on incidence rates of IRAEs,5 we adopted updated guidelines for routine laboratory monitoring on immunotherapy. These guidelines incorporate increased monitoring intervals and enhanced surveillance for diabetes mellitus, hypophysitis and adrenal insufficiency. Results: Our proposed schedule advises pre-treatment testing of FBC, U&E, LFTs, TFTs, serum glucose, HbA1c, ACTH and serum cortisol levels. Monitoring then occurs every 3-4 weeks with FBC, LFTs, U&E, TFTs, serum glucose, and routinely testing ACTH and cortisol for Ipilimumab and combination treatments only, for six months duration. After six months, the interval increases to monitoring every 6-8 weeks with the same tests. We have compared the cost of monitoring for one year using our guidelines versus NCCP guidelines,1,2,3,4 using pricing as per a single institution laboratory. We also compared the frequency of monitoring over one year with monitoring versus NCCP guidelines. Conclusions: We conclude that our proposed algorithm for monitoring for IRAEs is cost effective, despite more frequent monitoring of ACTH and cortisol, and carries a lower burden of testing for patients, when compared with monitoring as per current NCCP guidelines. [Table: see text]
Cost-effectiveness (CE) of regorafenib dose optimization schedule in metastatic colorectal cancer.
Authors: Barzi Afsaneh , Cho Sang K , Hay Joel W , Lenz Heinz-Josef , Ou Fang-Shu , Grothey Axel , Bekaii-Saab Tanios S.
Published: May 2019

e18367

Background: Regorafenib at 160mg daily 21/28 days is a standard therapeutic option in patients with metastatic colorectal cancer. However, the cost of treatment and management of its side-effects is more than the cost-effectiveness threshold for oncology drugs in US and many countries around the world. ReDOS (Regorafenib Dose Optimization Study), is a randomized phase II trial in refractory mCRC and established that weekly dose escalation of regorafenib over the conventional dosing is superior in the composite endpoint of safety and efficacy. We explored the impact of the new dosing strategy on CE of regorafenib. Methods: A Markov model was constructed to compare costs and effectiveness of regorafenib (standard), regorafenib (ReDOS), and best supportive care (BSC). Model inputs for clinical efficacy and safety were from the CORRECT trial for regorafenib (standard) and BSC, and the ReDOS study for regorafenib (ReDOS). The incremental cost-effectiveness ratios (ICERs) were reported to compare treatments. Model robustness was checked with univariate and probabilistic sensitivity analyses. The model used a US payer’s perspective with 5% annual discount rate, and all costs were measured in 2018 US dollars. Results: Regorafenib (ReDOS) dominated regorafenib (standard), producing higher quality-adjusted life years at a lower cost. When compared to BSC, regorafenib (ReDOS) resulted in the ICER of $112,705 while regorafenib (standard) resulted in the ICER of $384,687. The most influential parameters on the ICERs were efficacy and health state utility parameters under univariate sensitivity analysis. In probabilistic sensitivity analysis using cost-effectiveness acceptability curves, regorafenib (ReDOS) was more cost-effective than regorafenib (standard) and BSC in 70% of repetition at the willingness-to-pay threshold of $120,000 per QALY (Quality-Adjusted Life Year) and 98% at a WTP threshold of $150,000. Conclusions: Based on the outcomes demonstrated in the ReDOS study, the dose optimization strategy of regorafenib results in favorable cost-effectiveness under a typical US willingness-to-pay threshold of $150,000 per QALY.
Economic burden of immunotherapy as second-line treatment of patients with advanced non-small-cell lung cancer at a Latin American oncology center.
Authors: Barron Feliciano Barron , Cabrera Luis Antonio , Cardona Zorrilla Andres Felipe , Arrieta Rodriguez Oscar Gerardo
Published: May 2019

e18376

Background: Lung cancer is the leading cause of cancer-related mortality in México and worldwide. More than 80 percent of lung cancers are classified as non-small cell lung cancer (NSCLC). Immunotherapy has become integrated into the treatment of patients with specific genetic alterations, which has led to improvements in survival and quality of life. Pembrolizumab is a new drug approved in several countries for second-line therapy in non-small cell lung cancer (NSCLC) being programmed cell death ligand (PD-L1) positive. Methods: A retrospective study of medical records of 60 patients treated with immunotherapy as second-line treatment of advanced non-small-cell lung cancer was conducted at the National Institute of Cancerology (INCAN) in Mexico during 2016-2018. PD-L1 biomarker was not mandatory for receiving immunotherapy. The costs associated with the total costs of tretament were estimated as a mean value with confidence intervals of 95% confidence by costing the elements of treatment of the disease and adverse events as well the frequency of consultations, hospital stays, and monitoring obtained in the records. Costs are presented in US dollars. Results: The total mean monthly cost during immunotherapy was $1,649 (95% confidence interval [CI] = $1,484–$1,814), of which 93.8% represented immunotherapy costs, 5.4% drug application and monitoring, 0.8% adverse events treatment. We identified 30 potential patients per year candidates to receive immunotherapy as second line. From which the expected costs of treatment will be $49,476 [CI] = $44,528–$57,392), of which $41,766 are immunotherapy costs, application and monitoring represent $2,400 and the rest for adverse events. Conclusions: The therapeutic approach for the second-line treatment of patients with advanced non-small cell lung cancer (NSCLC) without actionable mutations has been revolutionized by the approval of new more efficacious drugs like pembrolizumab. Healthcare costs during immunotherapy treatment with pembrolizumab were largely attributed to anti-cancer therapy and less for adverse events. Pembrolizumab as second-line treatment of patients with advanced non-small-cell lung cancer, prolong overall survival, leading to fewer adverse events than chemotherapy.
Cost and time savings of subcutaneous trastuzumab (SC-T) in a public health system in Mexico.
Authors: Villarreal-Garza Cynthia , De la O-Maldonado Cristel , Díaz-Pérez Héctor , Mesa-Chavez Fernanda , García-García Marisol , Cardona-Huerta Servando , Peña-Curiel Omar
Published: May 2019

e18387

Background: The subcutaneous presentation of trastuzumab has been recently incorporated into the treatment regimen of HER2-positive breast cancer (BC). Its use has been associated with cost savings and reduced chair time, being especially suitable for public health systems. Aim: To estimate the cost savings of the use of SC-T compared to intravenous trastuzumab (IV-T) according to patient weight, and calculate the infusion time of SC-T in a tertiary healthcare facility at TecSalud from Feb 2018 - Jan 2019. Methods: From a total of 2068 oncological treatments, 756 corresponded to SC-T, either alone or concomitantly with chemotherapy (CT). For cost estimation, we considered $1,103 USD per SC-T vial, $1,162 USD per IV-T vial and $2.6 USD per mg of IV-T, as per governmental rates. We compared the actual treatment cost of 600 mg fixed SC-T dose with the hypothetical cost of administering IV-T at a dose of 6 mg/kg, considering its price per vial and per mg. The total time of SC-T infusion was reported. Results: Median patient weight for the 756 reported SC-T treatments was 72 kg (45 - 127 kg). Of these, 561 consisted of SC-T alone; and 56% had adjuvant, 34% neoadjuvant and 10% palliative intent. The estimated cost of the 756 doses of SC-T was $833,500 USD. Considering patients’ weight, 46% of the infusion treatments would have required 2 IV-T vials, with a total of 1105 vials and an absolute cost of $1,282,374 USD. Likewise, if cost per mg of IV-T is examined, we would have used 338,744 mg of IV-T, with an estimated cost of $894,284 USD. Approximate savings of SC-T use would reach $448,874 USD per vial payment and $60,784 USD per mg payment. The median time of SC-T only infusion was of 3 minutes (1 - 20 minutes); and no adverse effects were documented during its administration. Conclusions: The SC-T fixed dose (irrespectively of patients’ weight) results in significant practical and financial advantages as weight-adjusted dosing is not required. This is specially relevant in countries like Mexico, where > 70% of BC patients are overweight/obese, requiring higher doses of IV-T and resulting in greater expenses. Thus, the use of SC-T not only offers greater convenience to patients, but also reduces overall healthcare costs compared to standard IV infusion.
Phase II trial of pembrolizumab (MK-3475) in metastatic cutaneous squamous cell carcinoma: An updated analysis.
Authors: Yushak Melinda Lynne , Lawson David H. , Goings Monica , Mckellar Marjorie , Maynard Necia , Woodruff Kristin Sieja , Gorgoglione Caroline , McBrien Stephanie , Delman Keith A. , Lowe Michael C. , Kudchadkar Ragini Reiney
Published: May 2019

e21015

Background: Cutaneous squamous cell carcinomas (cSCC) are generally curable with surgery and/or radiation. Unfortunately, some patients develop locally advanced or metastatic disease, with an estimated 3900 to 8700 patients dying of cSCC in 2012. Aggressive disease is often associated with immunosuppression, and no treatment has shown an improvement in overall survival (OS). Recently the FDA has approved cemiplimab-rwlc which targets PD-1. This abstract provides an updated analysis and additional followup for patients treated with pembrolizumab which also targets PD-1. Methods: Clinical activity of pembrolizumab in cSCC patients was evaluated in patients who were not curable by surgery and/or radiation. Patients were treated with pembrolizumab 200mg IV every 3 weeks for up to 2 years. Tumor response was measured every 12 weeks using RECIST version 1.1. Response rate (RR) of pembrolizumab in metastatic cSCC was the primary objective. 6-month progression-free survival (PFS) and 1 year OS were secondary objectives. Results: 11 subjects have been enrolled thus far with a median age of 70.3 years. Two were female and all were Caucasian. ORR per RECIST criteria was 64% with 18% (2) having a complete response, 36% (4) a partial response, 36% (4) progressive disease (PD), and 9% (1) stable disease. The patient with stable disease had a clinical response and was eventually able to undergo surgery that rendered him without any evidence of disease. 6 month PFS for evaluable patients was 72%. Of those patients with a response, 50% had a durable response of 18 months or greater at the time of data cut-off. No subject deaths have occurred on study. Three grade 3 related-adverse events were noted (hepatitis and pneumonitis). Conclusions: Pembrolizumab is active in advanced cSCC. Responses appear durable and comparable to what has been seen in previous studies with the FDA-approved agent, cemiplimab. No new safety concerns were noted. Additional follow up is needed in order to establish an OS benefit. Clinical trial information: NCT02964559.
Clinical characteristics and treatments outcomes of patients with metastatic uveal melanoma (UM) in a Brazilian population: A retrospective unicentric study.
Authors: Campiolo Giovanna , De Barros E. Silva Milton Jose , Petaccia de Macedo Mariana , Rinck Jose Augusto
Published: May 2019

e21018

Background: Uveal melanoma is the most common primary ocular tumor in adults and accounts for 5% of all melanoma diagnoses in the United States. Approximately fifty percent of patients with uveal melanoma develop metastatic disease. The most frequent site of metastasis from UM is the liver (89 to 95% of the cases) and liver failure is the leading cause of death. To date, no systemic therapy has shown benefits in terms of overall survival (OS) in UM. Methods: We retrospectively analyzed clinical characteristics and aspects of response to systemic and local therapy of a cohort of 58 patients with UM who were treated in our institution from January of 2000 to December of 2017. Survival curves were calculated by Kaplan-Meier method and log-rank test. Results: Median age was 55y. 64% of the patients were female and 48,3% of them were caucasian. With a median follow-up time of 23 months, the median OS was 28,4 months. The median time between primary treatment and systemic relapse was 3.7 years. In 90% of the cases the liver was the unique site of progression. 12% patients had liver metastasectomy as local treatment, with OS of 102,3 months vs. 24,5 months ( p= 0,04) for no local treatment. 12% of the patients with liver methastasis perfomed regional treatment with intra-arterial chemotherapy (IAC) and 17% with chemoembolization (CE). The progression free survival (PFS) for regional treatment was 2.9 months (0,9-27 m); 4,25 months (0,9-27 m) for IAC and 2,9 months (0,9-27 m) for CE. There was no significant benefit in OS for locorregional treatment. As first line treatment, 29% of patients had chemotherapy, 10% had ipilimumab and 3,4% had anti-PD1. The median PFS for first line treatment was 2,49 months; 2 months for chemotherapy, 3,8 months for ipilimumab and 14 months for anti-PD1. The median PFS for second line treatment was 2,8 months and for third line was 2,3 months. There was no consistent clinical impact in OS for systemic treatment. Conclusions: The current systemic treatments available for cutaneous melanoma have limited efficacy in UM, so far none have yet proven a survival benefit. Locorregional therapies are relevant for patients with unresectable hepatic metastases. Resection of liver lesions in highly selected cases has the potential to improve patient outcomes, but the survival advantage may partially reflect patient selection.
A real-world study of recombinant human endostatin continuous intravenous infusion combined with chemotherapy in the treatment of advanced mucosal melanoma.
Authors: Liu Xin , Cao Jun , Meng Yanchun , Zhang Xiaowei , Xu Yu , Wang Chunmeng , Chen Yong , Yang Huijuan , Kong Yunyi , Luo Zhiguo
Published: May 2019

e21019

Background: There is no standard treatment for patients with advanced mucosal melanoma (AMM). Recombinant human endostatin (Endostar) combined with chemotherapy had been showed to improve the efficacy of advanced melanoma. This real world study was aimed to observe the efficacy and safety of endostar continuous intravenous infusion (Civ) combined with chemotherapy in patients with AMM. Methods: 23 patients with AMM treated with endostar plus dacarbazine or temozolomide plus cisplatin between April 2017 and December 2018 were collected. Endostar was given 105mg/m2 Civ168h (unlike the usual use of 7.5mg/m2/d d1-14) . 5 patients with local advanced disease received concurrent radiotherapy. Results: There were 11 males (48%) and 12 females (52%), with a median age of 58 years (30-72 years). Primary lesions were located in the nasal cavity and paranasal sinuses in 9 cases (39%), anorectum in 9 cases (39%), vagina in 3 cases (13%), esophagus in 1 case (4%), and choroid in 1 case (4%). There were 7 patients with local advanced disease and 16 patients with metastatic disease. 1 patient received prior anti-PD1 therapy, 1 patient received prior chemotherapy, the other 19 patients received no prior systemic therapy. A total of 21 patients underwent gene detection, there were 2 patients (10%) with BRAF mutation (one with V600E mutation, one with G606E mutation), 7 patients (33%) with NRAS mutation (3 with exon 2 mutation, 4 with exon 3 mutation), and 1 patient (5%) with KIT exon 11 mutation. Overall, 4 patients (13%) had CR, 4 patients (22%) had PR, 10 patients had SD (43%), and 5 patients (22%) had PD, resulting in a RR of 35% and a DCR of 78%. The 4 patients with CR were with localized disease and received concurrent radiotherapy. The RR were 44%, 33%, 33%, 0% and 0%, and the DCR were 100%, 67%, 67%, 0%, and 100% in patients with melanoma of the nasal cavity, anorectum, vagina, esophagus and choroid respectively. The median PFS was 7.5 months (95% CI: 1.0-14.0months). The median OS was 14.7 months (95% CI: 5.0-24.4months). Grade III/IV adverse events were leucopenia (13%), thrombocytopenia (13%), anemia (4%), nausea and vomiting (4%), elevated transaminase (4%), nasal hemorrhage (4%) and intestinal obstruction (4%). Conclusions: Endostar combined with chemotherapy is effective and safe in the treatment of AMM, especially for patients with melanoma of the nasal cavity and paranasal sinuses. For mucosal melanoma patients with local advanced disease, concurrent chemoradiotherapy may be a good choice. It deserves further study.