bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune related adverse effects (IRAEs) in patients with cancer who received immune checkpoint inhibitors (ICIs): A single center experience from rural Maine.
Authors: Patwari Anannya , Bhatlapenumarthi Vineel , Harb Antoine Joseph , Curtis Adam
Published: May 2020

e19265

Background: ICIs are used for a variety of malignancies and have shown to improve survival, but they are associated with IRAEs. We aim to identify the frequency and severity of new IRAEs and flares of preexisting autoimmune (AI) disorders excluding thyroid disorders in cancer patients treated with ICIs at our institution. Methods: We conducted a retrospective chart review analysis of all cancer patients who received ICIs: nivolumab, pembrolizumab, atezolizumab and durvalumab at the Northern Light Cancer Institute from June 2015 to March 2019. We excluded patients who received ipilimumab. We then studied those who developed IRAEs. Results: Out of 465 who received ICIs, 115(24.7%) developed IRAEs. 83 out of 298 (27.9%) nivolumab recipients, 20/121 (15.7%) pembrolizumab recipients, 5/26 (19.2%) atezolizumab and 7/20 (35%) durvalumab recipients developed IRAEs. Some patients had multiple toxicities. Median age at cancer diagnosis was 66 years, evenly split among males and females. Majority (63%) were treated for Lung cancer, followed by melanoma (20%) and genitourinary cancers (12%). Summary of new IRAEs are as noted in the table below. In patients with new IRAEs treatment was held in 29(6%) for a median duration of 7.2 wks. Upon rechallenge with the same ICI in 27 patients, 20(74%) tolerated and 7 did not leading to permanent discontinuation. Majority were treated with steroids and some required immunomodulators. Interestingly 39(8%) patients with underlying AI condition received ICIs. Of these 11(28.2%) developed flares, resulting in permanent discontinuation of drug in 4. The majority tolerated the treatment well. Treatment was permanently discontinued in 70(15%), 26(6%) required hospital admission for IRAEs. Pneumonitis was the most common toxicity necessitating treatment discontinuation and hospital stay. Conclusions: In real world setting the frequency and severity of IRAEs was more than the reported literature data, leading to higher rates of permanent discontinuation of treatment. [Table: see text]
Trends in lung cancer mortality between 2001 and 2017: An observational study in USA and EU.
Authors: Jani Chinmay , Marshall Dominic C , Singh Harpreet , Shalhoub Joseph , Salciccioli Justin
Published: May 2020

e19277

Background: The lung is the commonest site of cancer and has the highest worldwide cancer-related mortality. Past two decades has seen advancements in screening technologies and guidelines, as well as new modalities for treatment. Few studies have reported on lung cancer trends in the 21st century. Our study reports and compares trends in lung cancer mortality in the USA and European Union (EU). Methods: We utilized the World Health Organization (WHO) Mortality Database and Center for Disease Control (CDC) Wonder database. We extracted Lung Cancer mortality data from 2001 to 2017 based on ICD 10 system. Crude mortality rates were dichotomized by sex and reported by year. We computed Age Standardized Death Rates (ASDRs) per 100,000 population using the World Standard Population and USA Standard Population. Lung cancer mortality trends were compared using Joinpoint regression analysis. Results: We analyzed a data from a total of 26 EU countries and USA, of which 6 countries had data till 2017, 12 till 2016, 7 till 2015 and 2 till 2014. We observed that mortality in men was down-trending in all countries except Cyprus and Portugal. In females, there was an increase in mortality in 22 countries. Amongst EU nations, most recently (2017) Hungary had the highest ASDRs for both males and females (64.5/100,000 and 31.0/100,000), whereas the lowest mortality was in Sweden for males (17.3/100,000) and Lithuania for the females (7.58/100,000). Latvia had the highest Estimated Annual Percentage Change (EAPC) in male mortality (-9.6%). Based on recent most data, we saw that there was a significantly lower mortality in males amongst European nations that joined the EU pre-2004 as compared to those that joined the EU post-2004 (p = 0.006). In USA, ASDRs in males and females were 44.3/100,000 and 30.6/100,000, respectively, with EAPC of -5.1% and -4.2% in males and females, respectively. Conclusions: For the study period, we observed expected decrease in lung cancer mortality in males. In contrast, there was a gradual rising trend in lung cancer mortality amongst females. In addition, there was substantial variation between nations. USA has shown consistent downtrend since 2001 where as there have been fluctuations in trends in other EU nations.
Establishing the common oncology data model for the national biobank consortium of Taiwan.
Authors: Yi-Hsin Yang , Chen Li-Tzong , Huang Shiu-Feng
Published: May 2020

e19283

Background: Taiwan has 32 biobanks under Government’ governance. The Ministry of Health and Welfare have established a National Biobank Consortium of Taiwan to unify the specimen quality and the medical record database. The total recruited participants exceed 350,000. The National Health Research Institutes in Taiwan hold the responsibility of establish a common data model for aggregating data elements from electronic health records (EHRs) of institutes through direct feeds. The goals are to assemble a set of common oncology data elements and to facilitate cancer data interoperability for patient care and research across institutes of Biobank Consortium. Methods: We first conduct a thorough review of available EHR data elements for patient characteristics, diagnosis/staging, treatments, laboratory results, vital signs and outcomes. The data dictionary was organized based on HL7 FHIR and also included data elements from Taiwan Cancer Registry (TCR) and National Health Insurance (NHI) Program, which the common definition has already been established and implemented for years. Data elements suggested by ASCO CancerLinQ and minimal Common Oncology Data Elements (mCODE) are also referenced during planning. The final common model was then reviewed by a panel of experts consisting oncologists as well as data science specialists. Results: There are finally 9 data tables with 281 data elements, in which 248 of them are from the routinely uploaded data elements to government agencies (TCR & NHI) and 33 elements are collected with partial common definition among institutes. There are 164 data elements which are to be collected one observation per case, while 117 elements will be accumulated periodically. Conclusions: A comprehensive understanding of genetics, phenotypes, disease variation as well as treatment responses is crucial to fulfill the needs of real-world studies, which potentially would lead to personalized treatment and drug development. At the first stage of this project, we aim to accumulate available EHR structured data elements and to maintain sufficient cancer data quality. Consequently, the database can provide real-world evidence to promote evidence-based & data-driven cancer care.
Real-world (RW) systemic treatment patterns and clinical outcomes in locally advanced (LA) and recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC) patients (pts).
Authors: Vo Thao , Boyd Marley , Espirito Janet L. , Gumuscu Burak , Chirovsky Diana Romana , Robert Nicholas J. , Swaby Ramona F. , Zhou Wei , Cowey Charles Lance
Published: May 2020

e19284

Background: Data is limited on RW systemic treatments, objective response rate (ORR), response duration (DOR), overall survival (OS), and time-to-treatment discontinuation (TTD) for cSCC. Clinical trials (CTs) use RECIST criteria for response assessment; however, frequency of follow-up imaging and availability/precision of tumor lesion measures outside of trials can vary across pts. Understanding the types of image-informed responses and outcomes available in clinical practice may inform RW study design and interpretation. Methods: Adults with LA and R/M cSCC receiving first-line (1L) systemic treatment from 09/04/2014 to 06/30/2017 in US Oncology community practices, with follow-up to 06/30/2018, were included. Baseline radiologic scan was required; pts in CTs or who had concurrent cancers or immunosuppressive disorders/treatments were excluded. The primary endpoint was RW ORR using RECIST 1.1, based on tumor lesion sizes (if available) in imaging reports from the iKnowMed electronic health record. If RECIST could not be applied, physician-assessed responses were used. Pts not evaluable for response were classified as non-responders. DOR, OS, and TTD were assessed using Kaplan-Meier methods. Results: 51 (11 LA + 40 R/M) cSCC pts were eligible. Median age was 76 yrs, 80% male, 86% Caucasian, 65% ECOG PS of 0/1. The primary location was head/neck in 67%. The most common 1L regimens were cetuximab (51%), carboplatin + paclitaxel (22%), and cisplatin (6%). Conclusions: Cetuximab was the most common treatment. OS and TTD in advanced cSCC were short. RW ORR was lower using RECIST than with physician assessment; however, few pts were evaluable by RECIST due to differences in available data in prospective vs. retrospective settings. [Table: see text]
Real-world burden of chemotherapy-induced myelosuppression: Results of a U.S. online survey of patients with cancer.
Authors: Epstein Robert S. , Aapro Matti S. , Basu Roy Upal K. , Salimi Tehseen , Krenitsky JoAnn , Leone-Perkins Megan L. , Crawford Jeffrey
Published: May 2020

e19299

Background: Research into the real-world impact of chemotherapy (CT)-induced myelosuppression on patients’ lives is limited. This study aimed to investigate the impact of CT-induced myelosuppression on patients with lung, breast, or colorectal cancer (CRC). Methods: Following Institutional Review Board approval to proceed with exception, a survey of participants identified from an online U.S. patient panel was conducted in Nov/Dec 2019. Participants who had been treated with CT in the past year and experienced ≥1 episode of myelosuppression (‘a decrease in bone marrow activity resulting in the reduced production of blood cells’) were eligible for participation. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection. Descriptive statistics were used to summarize key findings. P values were calculated using the Chi-square test. Results: 301 participants completed the online survey (breast cancer, n = 153 [51%]; lung cancer, n = 100 [33%]; CRC, n = 48 [16%]). Most participants were aged > 40 years, 60% were female, 60% were currently employed, and 75% had been diagnosed with cancer within the last 3 years. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Fatigue was the most commonly noted side-effect of CT (reported by 72% of participants), with 55% of participants rating it as highly bothersome (9 or 10 on a 1–10 scale of ‘bothersomeness’). Most participants (89%) considered myelosuppression to have a moderate or major impact on life (major life impact, 40%; moderate life impact, 49%; minor life impact, 12%). Patient-reported impact of myelosuppression was significantly higher among participants aged < 50 years vs those aged ≥50 years (p = 0.01); however, no significant differences were observed when participants were stratified by sex, employment status, comorbidities (depression, diabetes, hypertension), or type of cancer. Significantly more participants with fatigue, considering themselves to have a weakened immune system, or noticing easy bruising/bleeding reported a major life impact vs those without these side effects (44% vs 27%, 52% vs 26%, and 50% vs 34%, respectively; all p < 0.01). Conclusions: These data provide further insights into the substantial real-world patient burden of symptoms arising from CT and associated with myelosuppression. Preventing or proactively managing CT-induced myelosuppression could have a major impact on patients’ quality of life.
The master observational trial–a novel method to unify precision oncology data collection.
Authors: Dickson Dane J. , Johnson Jennifer Maria , Bergan Raymond C. , Owens Rebecca , Subbiah Vivek , Kurzrock Razelle
Published: May 2020

e19313

Background: The Master Observational Trial (MOT) was recently created as a new master protocol that hybridizes the power of master interventional trials with the richness of real-world data (Cell, 2020). The MOT can be described as a series of prospective observational studies that are tied together through a common protocol, infrastructure, and organization. The MOT has broad application in many disease states but is particularly powerful in oncology. We herein expand our prior work to describe key details regarding how the MOT concept can fill multiple unmet needs in oncology. Methods: Through published information, white papers, and expert opinions we identified key unmet needs of oncology stakeholders. We reviewed the publicly available information of structure, organization, and data availability of the five largest genomic-outcome real-world data efforts. Common concerns included variability and reliability of biomarkers, the scientific rigor in real-world data, data silos, patient consent, and duplicated or disparate activities. We then determined how a specific application of the MOT in oncology could answer stakeholder concerns, integrate with current efforts, and also how to provide a model that would be equally valuable to academic and community clinics. Results: We identified significant scientific challenges with many of the current oncology real-world datasets in answering key concerns of stakeholders. We developed the Master Registry of Oncology Outcomes Associated with Testing and Treatment (ROOT) as the first national implementation of an oncology-centric MOT. We modeled how ROOT could fill scientific gaps in current data efforts and integrate with interventional and real-world efforts and help answer key concerns of stakeholders. We also identified solutions that would allow community and academic groups to participate in the same effort. Conclusions: An oncology-centric MOT has the potential to improve the quality of RWD in oncology and advance precision oncology in ways that are not fully addressed by current retrospective efforts. Reference Dickson DJ, Johnson J, Owens R, Bergan R, Subbiah V, Kurzrock R. (2020). The Master Observational Trial: A New Class of Master Protocol to Advance Precision Medicine. Cell 180, 9-14. Clinical trial information: NCT04028479 .
MSI/MMR test usage and checkpoint inhibitor practices in Europe.
Authors: Smith Bradley , Hodge Jeffrey , Anger Caroline , Manuguid Fil , Jindal Kriti
Published: May 2020

e19327

Background: Micro-Satellite Instability (MSI) or DNA Mismatch Repair (MMR) is an established prognostic test associated with response to chemotherapies in Lynch Syndrome, colorectal cancer and other indications. Recently, MSI/MMR status has been shown to predict response to immune checkpoint inhibitors (CPI). Pembrolizumab has been approved in the USA for MSI-high or mismatch repair deficient patients for all indications. A similar approval has not been obtained in the EU. This data research project examined MSI/MMR testing in Europe and its possible association with use of CPI therapies. Methods: This study was conducted using Oncology Dynamics, an IQVIA oncology cross-sectional survey, collecting anonymized real-world patient-level data. 97,807 and 96,111 drug treated patients for solid tumors in 2018 & 2019, respectively, were collected across 5 European countries (France, Germany, Great Britain, Italy and Spain). Data included number of patients tested for MSI/MMR, results of the test, site and funding type, and the drug(s) prescribed. Results: European MSI/MMR test rates ranged from 3% in Italy in 2018 to 12% in France in 2019. Testing rates increased modestly in all countries over the period. Testing rates were determined in 25 specific indications plus all other indications. As expected, rates were highest in colorectal and stomach cancer. Testing was observed in other indications including Esophageal, Brain and Melanoma all with rates of 10% or higher. The percentage of MSI-High patients ranged from a low of 13% in Italy in 2019 to 26% in France in 2019. Finally, 17% of MSI-High patients are treated with CPIs compared to 5% of MSI-Low patients across all countries in 2019. Conclusions: The results over two years and almost 200,000 patients present insights into the use of MSI testing in 5 European countries. MSI testing is performed in many indications in addition to those typically associated with the biomarker. The increase in CPI use in MSI-High patients suggest that test results may impact use of checkpoint inhibitors although causation may not be inferred from the current analysis. However, the correlation suggests that further analysis is warranted.
Time from diagnosis to 1st line immunotherapy (IOT) and its challenges, in a retrospective, multicenter study of Israeli patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Shimony Udi , Hasid Lior , Deutsch Irad , Malki Eliran , Vorobiof Daniel A.
Published: May 2020

e19346

Background: The importance of timely treatment of advanced NSCLC and timeline measurements have been the subject of reported studies. Real world evidence data (RWED) via EHR and cutting-edge technology paired with Belong.life pts engagement platform, was evaluated in Israeli pts with NSCLC, members of Belong.life community. Timelines from diagnosis to start of IOT were analyzed by data scientists using AI and machine learning engines. Methods: 30 Israeli pts with advanced NSCLC, members of Belong.life, the largest global social media platform for cancer pts and caregivers, were screened during 2016-8. Demographics, time of diagnosis, time of starting IOT and reasons for treatment delays were documented. Results: 18 pts (60%) were males and 88% had Stage 4. Most pts (87%) were diagnosed during 2017-8. 46 % were < 60 yrs and 54% > 61 yrs. 18 (60%) pts received only pembrolizumab while 11 (37%) pts had it in combination with various chemotherapy drugs. 1 pt received single agent nivolumab. According to the dates reported by 22 (76%) pts, the median time from diagnosis to IOT initiation was 37 days( < 20-96) with 13(59%) starting the treatment in < 40 days. Most common delay causes were due to waiting for genetic tests to define targeted therapy (38%), protracted diagnostic phase (38%) and bureaucratic issues in 27%. Study limitations included its retrospective nature, a convenience sampling, and partial reliance on pts recall of dates. Conclusions: Healthcare systems are seeing an increase in the incidence of most cancers. We report marked variability in time to initiation of 1st LOT therapy of Israeli pts with advanced NSCLC. The common reasons for the delays were obtaining the molecular tests results in order to define targeted drugs and as more targets and their therapies become available this period might increase. Treatment delays are likely to have a negative impact on pts well-being, quality of life and long-term prognosis. Speeding up diagnosis and treatment planning process could decrease pts waiting time, improve their quality of life and expectancy, therefore consideration to the development of a time to treatment protocol should be prioritized.
Blockchain-authenticated sharing of cancer patient genomic and clinical outcomes data.
Authors: Burns Shohei , Collisson Eric Andrew
Published: May 2020

e19358

Background: Efficiently sharing health data produced during standard care could dramatically accelerate progress in cancer treatments but various barriers make this difficult. Not sharing these data to ensure patient privacy is at the cost of little to no learning from real-world data produced during cancer care. Furthermore, recent research has demonstrated a willingness of cancer patients to share their treatment experiences to fuel research, despite potential risks to privacy. The objective of this study was to design, pilot, and release a decentralized, scalable, efficient, economical, and secure strategy for dissemination of de-identified clinical and genomic data with a focus on late stage cancer. Methods: We created and piloted a blockchain-authenticated system to enable securely sharing de-identified patient data derived from standard of care imaging, genomic testing, and electronic health records (EHR), called the Cancer Gene Trust (CGT). We prospectively consented and collected data for a pilot cohort (n = 18), which we uploaded to CGT. EHR data were extracted from both a hospital cancer registry and a common data model format to identify optimal data extraction and dissemination practices. Specifically, we scored and compared the level of completeness between two EHR data extraction formats against the gold-standard source documentation for patients with available data (n = 17). Results: While the total completeness scores were greater for the registry reports than the common data model, this difference was not statistically significant. We did find that some specific data fields, such as histology site, were better captured using the registry reports, which can be used to improve the continually adapting common data model. In terms of the overall pilot study, we found that CGT enables rapid integration of real-world cancer patient data in a more clinically useful timeframe. We also developed an open-source web application to allow users to seamlessly search, browse, explore, and download CGT data. Conclusions: Our pilot demonstrates the willingness of cancer patients to participate in data sharing and how blockchain-enabled structures can maintain relationships between individual data elements while preserving patient privacy, empowering findings by third party researchers and clinicians. We demonstrate the feasibility of CGT as a framework to share health data trapped in silos to further cancer research. Further studies to optimize data representation, stream, and integrity are required.
Examining the relationship between the clinical benefit of oncology drug indications and the time from pan-Canadian Oncology Drug Review (pCODR) recommendation to public reimbursement.
Authors: Thomson Sasha , Everest Louis , Witzke Noah , Delos Santos Seanthel , Cheung Matthew C. , Chan Kelvin K.
Published: May 2020

e19360

Background: We examined if publicly reimbursed oncology drug indications with evidence of high clinical benefit, as measured by the American Society of Clinical Oncology Value Framework v2 (ASCO-VF), and European Society for Medical Oncology Magnitude of Clinical Benefit Scale v1.1 (ESMO-MCBS), received reimbursement status faster than those with lower clinical benefit from the time of pCODR recommendation. Methods: Oncology drug indications that received pCODR recommendations between Jan 2012 and July 2018 were identified. Indications that did not receive provincial reimbursement, without notice of compliance, or received a negative pCODR recommendation were excluded. The relationship between clinical benefit, as measured by ASCO-VF and ESMO-MCBS, and the time to reimbursement was evaluated using Spearman correlation coefficient, univariable, and multivariable linear regression analyses. Results: Overall, 84 indications met inclusion criteria yielding 80 ASCO-VF and 66 ESMO-MCBS scores. The mean ASCO-VF and ESMO-MCBS scores were 38.8 (SD = 23.8) and 3.0 (SD = 1.1) respectively. Higher ASCO-VF and ESMO-MCBS scores had low correlation with shorter time to provincial funding, (rho = -0.15, 95%CI -0.24, -0.06) and (rho = -0.25, 95%CI -0.34, -0.16) respectively. Univariable analyses showed that manufacturer reported incremental cost effectiveness ratio (ICER) values, year of pCODR recommendation, province and cancer type were associated with time to public reimbursement (all p < 0.0001). After adjusting for potential confounders in the respective multivariable analysis, ASCO-VF (p = 0.29) and ESMO-MCBS (p = 0.15) scores were not significantly associated with time to public reimbursement. Year of pCODR recommendation remained associated with time to public reimbursement (p < 0.001). Earlier years (2012-2014) had a shorter time to reimbursement (mean = 10.4 months) than later years (2015-2018) (mean = 14.5 months). Other factors that were associated with time to reimbursement in multivariable analysis were province (p < 0.001) and cancer type (p < 0.001). Conclusions: Currently, oncology drug indication with evidence of high clinical benefit do not appear to be funded faster than those with low clinical benefit. This suggests the need to prioritize cancer drug indications based on clinical benefit in order to allow for timely public reimbursement of cancer drugs with higher clinical benefit to patients.
Cost savings of biosimilar pegfilgrastim in a Medicare OCM population.
Authors: Webster Jennifer , Smith Robert E. , Wieland Danielle , Verniero John , Scott Jeffrey A.
Published: May 2020

e19362

Background: Pegfilgrastim is a key supportive care agent in oncology patients, providing significant febrile neutropenia prophylaxis for patients on chemotherapy. However, pegfilgrastim also accounts for 5.3% of the total cost of cancer care for all patients in the Oncology Care Model (OCM). Fluctuations in the cost or quantity of pegfilgrastim can have significant impact on a practice’s performance under OCM. One such cost fluctuation is the introduction of biosimilars to the marketplace. This study seeks to understand how CMS reimbursement for pegfilgrastim has been impacted by the introduction of two pegfilgrastim biosimilars into the market. Methods: We tracked average CMS reimbursement for pegfilgrastim (Neulasta, Udenyca and Fulphila) from 7/1/2016 through 6/30/2019. We compared the average reimbursement and the average change in reimbursement before and after the introduction of biosimilars. Results: Prior to the introduction of biosimilars, the Medicare Part B reimbursement (80% of ASP +6%) of pegfilgrastim increased at a steady rate of $292 per year through the first 30 months of the OCM program, resulting in an average reimbursement of $3636 per administration in Q3 2018. However, since the introduction of biosimilars, average pegfilgrastim reimbursement has held steady, averaging $3543 for the time period from 7/1/2018 through 6/30/2019. The change in reimbursement has decreased from $292/year to -$93/year. Conclusions: In 2018, 88,847 Medicare patients received pegfilgrastim, resulting in $1.39 billion in Medicare reimbursement. Assuming that the patterns we’ve detected in our OCM data sample can be applied to the general Medicare population, we have estimated that the introduction of biosimilars resulted in a $4.8 million in savings (1.39%) compared with what the total reimbursement would have been without biosimilars in the market in Q4 2018. This bending of the cost curve is projected to result in savings of $79.1M (5.7%) in 2019 and $157.9M (11.5%) in 2020. Importantly, most of this cost containment is not due to patients utilizing biosimilars. 90.6% of patients in Q2 2019 are still receiving branded pegfilgrastim. However, the introduction of biosimilars has caused even the branded agent to stabilize and possibly even drop net acquisition cost prices. Introduction of biosimilars has created enough pressure on the market to result in significant cost savings, increasing the overall value proposition of pegfilgrastim. This results in significant cost saving to CMS, and also makes it easier for practices participating in OCM to have successful financial outcomes.
Financial toxicity in patients with multiple myeloma participating in clinical trials: A U.S. Food and Drug Administration pooled analysis.
Authors: King-Kallimanis Bellinda , Chen Ting-Yu , Kanapuru Bindu , Bhatnagar Vishal , Kluetz Paul Gustav
Published: May 2020

e19370

Background: Financial toxicity (FT) is a major concern for patients receiving standard cancer treatment, and FT can lead to worse cancer outcomes. However, little is known about the FT of patients enrolled in clinical trials (CT). While investigational treatment may be provided by sponsors free of charge, patients are subject to increased clinic visits (ie, missed workdays, travel costs) and still bear the cost of usual care. This analysis evaluates patient-reported FT in multiple myeloma (MM) trials submitted to US FDA and explores the relationship between baseline FT and overall response rate (ORR). Methods: We pooled data from 9 MM registration CTs submitted to the FDA that included the EORTC Quality of Life questionnaire (QLQ-C30). The QLQ-C30 includes an item asking patients “Has your physical condition or medical treatment caused you financial difficulties?”. We looked at proportion of patients at baseline reporting any FT and their ORR. We also report prevalence, incidence and change from baseline FT at 3 and 6 months. Results: 5,667 patients answered the FT item. Mean age of patients was 65 years, 55% were male, 85% were white and 6% were enrolled in the US. Approximately a third of patients reported experiencing any FT at baseline, 3 and 6 months. When compared to their baseline, 69% of patients had unchanged FT and 14% had worse FT at both 3 and 6 months. The incidence of new cases of FT at 3 months was 17% and at 6 months 7%. The ORR in patients who reported any FT at baseline was 69% compared to 72% in patients with no baseline FT, and was similar regardless of the degree of FT. Conclusions: Few studies have investigated FT in a large sample of CT participants. In this pooled analysis of patients enrolled in MM CTs, approximately a third of patients reported FT associated with their physical condition or medical treatment at baseline and throughout the trial. A small percentage of patients experienced worsening FT during the trial and a small percentage went from no FT to reporting any FT. The impact of baseline FT on ORR was small. Limitations of this preliminary analysis include missing patient level or group level insurance status, socio-economic status and other important determinants of health.
Do we consider to apply the value framework of cancer drugs to clinical practice and health insurance coverage in Korea?
Authors: Kim Do Yeun , Ha Hyerim , Lee Hee Yeon , Koo Dong-Hoe , Han Hye Sook , KIM Hee JUN , Oh Sung Yong , Bae SeungJin , Bae Green , Cho Jae-Young , Kang Jin-Hyoung
Published: May 2020

e19391

Background: Emerging oncology drugs such as targeted agents and immune checkpoint inhibitors (ICIs) have brought dramatic advances in cancer treatment, while rapid rise in the drug cost. In Korea, the policy of expansion of health insurance coverage has improved accessibility to high-priced oncology drugs through their registrations in reimbursement list. However, this made a considerable impact on the financial burden of national health insurance. The objective of this study was to assess the awareness and perceptions of medical oncologists about the value frameworks of cancer drugs in Korea. Methods: We collected the data from survey for 102 medical oncologists at cancer conference. They were asked about prioritization among multiple considerations when they prescribe cancer drugs, The second question was awareness of value frameworks such as American Society of Clinical Oncology (ASCO) value framework and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Additionally, potential application of value framework to the decision on reimbursement coverage was included. Results: The majority of respondents (90%) chose clinical efficacy as the most important factor when they selected oncology drug for cancer patients. Safety/tolerability and drug cost were followed as 5.9% and 1%, respectively. Meanwhile, the order of priority of considerations for ICIs treatment was as follows: clinical efficacy (74.5%), drug costs (13.7%), and safety/tolerability (9%). More than half of those questioned (53.9%) were already aware of ASCO value framework and ESMO-MCBS, while 26.5% did not recognize them at all. Over 90% of respondents agreed with the need for development of new value framework tool which can be complementary to current valuation system for oncology drugs. Oncologists responded positively to the necessity of the assessment tool as a criterion for reimbursement registration (84.3%) as well as post-reimbursement re-evaluation (89.2%). Conclusions: Our results suggest that value assessment tool of oncology drug be necessary for providing medical evidences for clinical decision and for determination to health insurance reimbursement in Korea.
Assessing the value of cemiplimab for adults with advanced cutaneous squamous cell carcinoma (CSCC): A cost-effectiveness analysis.
Authors: Paul Eleanor , Kuznik Andreas , Keeping Sam , Chen Chieh-I , Sasane Medha , Xu Yingxin , Konidaris Gerasimos , Atsou Kokuvi , Ayers Dieter , Ruiz Emily S , Khushalani Nikhil I. , Cope Shannon
Published: May 2020

e19397

Background: Cemiplimab is a high-affinity, human, hinge-stabilized, monoclonal antibody that potently blocks the interactions of programmed cell death-1 (PD-1) with programmed cell death ligand-1 (PD-L1) and PD-L2. In September 2018, cemiplimab-rwlc became the first systemic therapy approved by the US Food and Drug Administration for the treatment of patients with advanced CSCC ineligible for curative surgery or radiotherapy. In a single-arm Phase II study (NCT02760498), cemiplimab demonstrated substantial antitumor activity, durable responses, and acceptable safety profile in patients with advanced CSCC. The aim of this analysis was to evaluate the cost-effectiveness of cemiplimab in patients with advanced CSCC from a US payer perspective. Methods: A partitioned survival model was developed to assess the cost-effectiveness of cemiplimab versus historical standard of care (SOC). All inputs were identified based on a systematic literature review (SLR), which was supplemented by expert opinion where necessary. The clinical inputs for cemiplimab were based on the individual patient data from the cemiplimab Phase II trial, whereas for SOC, the analysis was based on a pooled analysis of single-arm clinical trials and retrospective studies evaluating chemotherapy and epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and gefitinib) identified via the SLR (6 of the 27 included studies). Overall survival and progression-free survival were extrapolated over a lifetime horizon using parametric functions consistent with guidance from the National Institute for Health and Care Excellence Decision Support Unit. Costs were included for drug acquisition, drug administration, management of adverse events, subsequent therapy, disease management, and terminal care. Unit costs were based on published 2019 US list prices. Results: In the base case, cemiplimab versus SOC resulted in an incremental cost-effectiveness ratio (ICER) of $99,024 per quality adjusted-life year (QALY), where incremental costs and QALYs were $372,425 and 3.76, respectively. At a willingness-to-pay threshold of USD $150,000 per QALY, the probabilistic sensitivity analysis suggests a 91% probability that cemiplimab is cost-effective when compared to SOC. Scenario analyses resulted in ICERs ranging from $90,326 to $147,944. Conclusions: Compared with historical SOC, cemiplimab is a cost-effective use of US payer resources for the treatment of advanced CSCC and is expected to provide value for money.
Affording Immune Checkpoint Inhibitors (ICI) in the treatment of advanced non-small cell lung cancer (NSCLC): Argentinean National Cancer Institute (ANCI) perspective.
Authors: Gabay Carolina , Pesci Santiago , Caldano Johana , Diaz Maria Celeste
Published: May 2020

e19404

Background: ICI agents proved clinical effectiveness in metastatic NSCLC; irrespectively PDL1 expression, but they increase costs considerably. Thus its cost-effectiveness (CE) needs to be established in low and middle-income countries. We aimed to assess CE of Pembrolizumab plus carboplatin and pemetrexed (PCP) vs. carboplatin and pemetrexed (CP) in the first-line setting for non-squamous NSCLC, according to PDL1expresion, in Argentinian public healthcare system (APHS). Methods: Clinical outcomes, utilities, and transition probabilities were collected from the available literature (Keynote 189/024) after a systematic review. The certainty of evidence according to GRADE methodology was qualified as high. A Markov model was developed. Model outcomes were measured in quality adjusted-life-years (QALY) and CE was estimated as the incremental cost-effectiveness ratio (ICER) over a 20 years time horizon. Only direct costs were considered from a public price database of the drugs accounted in the model. The WHO ICER threshold, defined as 1-3 GDP per capita, was selected to established CE. Sensitivity analyses were performed to assess the robustness of results. Results: In PDL1≥ 50 % subgroup, PCP increased life expectancy of patients by 1.06 QALY for an incremental cost of USD 71.551 vs. CP with an ICER of 67.352 per QALY. An indirect comparison of PCP vs. Pembolizumab monotherapy found no differences in QALY estimates, however, it was associated with an incremental cost of USD 5.516. QALY estimate for PDL1 1-49% was 0.73 with an ICER of USD 85.984/ QALY gained. PDL1 < 1% obtained a QALY of 0.42 related to the largest ICER (USD 97.095) for the same comparison. The sensitivity analyses using a threshold between 1- 3 Argentinian GDP per capita in 2018 (USD 11.8602) found that PCP has no chance of being considered CE in untreated NSCLC patients. If a 6 GDP threshold is adopted in PDL1≥ 50 %, PCP would have a 50% possibility of being CE. Conclusions: This model was part of the decision-making process in the development of treatment guidelines for metastatic NSCLC in the ANCI. PCP cannot be considered acceptable for the APHS. Strategies to reduce costs are mandatory to improve affordability in our region.
Reducing time to treatment and patient costs with breast cancer: The impact of patient visits.
Authors: Sittenfeld Sarah , Greenberg Zachary , Alhilli Zahraa , Abraham Jame , Moore Halle C. F. , Grobmyer Stephen R. , Monteleone Emily Elizabeth , Tullio Katherine , Shah Chirag
Published: May 2020

e19407

Background: The purpose of this study was to evaluate the impact of a continuous improvement process aimed at reducing time to treatment on minimizing the number of days spent to complete pre-treatment visits and the associated costs for patients with non-metastatic breast cancer. Methods: System-wide initiatives were implemented in 2015 to minimize time to treatment initiation (TTI), by incorporating lean process strategies and enhanced coordination. Patient and treatment information was obtained through an IRB-approved registry for the years 2015 and 2018. Average number of days spent to complete visits, TTI, and associated patient costs including driving expenses, parking, food, childcare, and lost wages were calculated and compared between the years 2015 and 2018. Results: In 2015, the median TTI was 43.5 days and the average number of separate days spent to attend multidisciplinary visits prior to first treatment was 1.86. These were reduced to 29 days and 1.52 visits, respectively, in 2018 (p < 0.0001 for both). When evaluating treatment visits by surgical procedure, the average number of visits was reduced regardless of surgical procedure. The average number of visits was highest for patients undergoing mastectomy with reconstruction (2.34 in 2015, reduced to 1.65 in 2018, p < 0.0001). A single visit to complete treatment planning was associated with patient costs of $249 as compared with multiple trips costing $491 for 2 visits and up to $1,226 for 5 visits. Conclusions: In breast cancer patients, implementing a continuous improvement process to reduce time to treatment was associated with fewer visits required prior to treatment initiation, resulting in lower patient costs.
Measurements of Mcl-1 protein dependencies using dimerization-specific antibodies as predictive biomarkers for BH-3 mimetic class therapies in AML.
Authors: Cardone Michael H. , Kinloch Andrew , Canakci Mine , Ge Jingping
Published: May 2020

e19505

Background: The anti-apoptotic Bcl-2 family proteins facilitate pro-survival and resistance to anti-cancer therapies. Measuring the function of these proteins has shown utility in predicting response to treatment. A biomarker platform that assesses the functionality of these proteins by measuring BH3 mediated signaling potential in individual patients’ cancers, could provide a potential guiding platform for treating AML. In AML venetoclax is becoming widely prescribed and highly effective in combination with other drugs. Recent data indicate that Mcl-1 dependence is a resistance factor to venetoclax and that methods for identifying this could provide guidance for combination treatments. We are developing a technology to directly measure the occurrence of heterodimers of Mcl-1, or Bcl-xL, bound to pro-apoptotic BH3-only protein Bim. These measurements are combined in algorithms developed to indicate the cancer cell apoptotic priming state and offer great potential for identifying best AML treatment options. Methods: Monoclonal antibodies against conformation-specific epitopes induced in Mcl-1/Bim and Bcl-xL/Bim protein complexes were made. Selective bonding of Heterodimer Specific Mcl-1 Bim (HSMCB) and Heterodimer Specific Bcl-xL Bim (HSBXB) mabs were confirmed using ELISA, fluorescence polarization, immunofluorescence microscopy and flow, and by immunohistochemistry in genetically defined cell lines and in AML patient biopsied samples. Results: We show that HSMCB signal depends on both Mcl-1 and Bim protein levels while HSBXB requires Bc-xL and Bim levels. The relative signals of HSMCB to unbound Mcl-1 signal ([HsMcB]/[Mcl-1]) provide a biomarker for Mcl-1 dependence. We carefully established binding metrics that correlate to drug response in cell lines. The pharmacological disruption of these complexes is monitored by the ratiometric readouts that serve as predictive biomarkers for BH-3 mimetic drugs in AML cells. Conclusions: Mcl-1 dependence is a predictive biomarker for venetoclax resistance and for response to Mcl-1 targeted therapies. Flow cytometric and IHC based measurements of a heterodimer complex offer a direct and simpler approach that harbors potential for use in clinical settings. Additional antibodies targeting Mcl-1/Bak and Bcl-2/Bim complexes are being tested.
Outcomes of myeloablative, T cell deplete unrelated donor hematopoietic stem cell transplantation at a single center.
Authors: Gaballa Mahmoud , Jang Albert , Hamad Hussein , Bulsara Shaun , Wu Meng-Fen , Carrum George , Ramos Carlos Almeida , Kamble Rammurti , Hill LaQuisa , Pingali Sai Ravi , Vu Ngoc , Scholoff Audrey , Obi Gloria , Heslop Helen E. , Lulla Premal D.
Published: May 2020

e19525

Background: Myeloablative conditioning (MAC) and unrelated donor (UD) hematopoietic cell transplantation (HCT) are associated with increased non-relapse mortality (NRM) compared with matched related donor (MRD) HCT [18%, 21%, and 32% for MRD, Matched UD (MUD), and mismatched MUD (MMUD), respectively, p < 0.001] (Saber et al, 2012). Our center uses alemtuzumab as means of T cell depletion to mitigate NRM risk in UD HCT. Here, we report outcomes utilizing this strategy. Methods: We retrospectively analyzed adult patients (pts) who received alemtuzumab-based T cell deplete MAC UD HCT from August 2012 to December 2017. Outcomes were estimated via Kaplan Meier and cumulative incidence methods. Results: Sixty-eight pts underwent T cell deplete MAC UD HCT for AML/MDS (n = 32), ALL (n = 18), lymphoma (n = 5), and other diseases (n = 13). Thirty-nine (57.4%) underwent a MUD HCT, while 29 (42.4%) underwent a MMUD (≤ 9/10 match) HCT. Median follow up was 35.5 months (m) (range 1.5 – 71.1). Median age was 46 years (range 21 - 68), 58.8% were male. Nineteen AML pts (67.9% of all AML) were considered high risk defined as secondary AML (n = 3), CR2 or more (n = 9), primary induction failure (n = 6) or having gross residual disease at time of HCT (n = 1). At 24 m, overall survival (OS) for the entire cohort was 65.3% (95%CI (CI) 53.5%- 77.2%), GVHD relapse-free survival (GRFS) was 54.8% (CI 42.8%- 66.9%), NRM was 10.4% (CI 4.5%- 19.2%), and relapse incidence (RI) was 27.3% (CI 17.1%- 38.5%). None of the 68 pts had graft failure or rejection. In the AML/MDS cohort, at 24 m OS was 52.3% (CI 33.9%- 70.7%), GRFS was 41.4% (CI 23.9%- 59%), NRM was 9.7% (CI 2.4%- 23.2%), and RI was 39.1% (CI 21.8%- 56.2%). Non-AML/MDS pts at 24 m had OS, GRFS, NRM and RI of 76.8% (CI 62.6%- 90.9%), 66.7% (CI 51.3%- 82.08%), 11.1% (CI 3.4%- 23.9%), and 16.7% (CI 6.6%- 30.6%), respectively. The table summarizes our outcomes. Conclusions: We show that alemtuzumab-based MAC conditioning for UD HCT has the benefit of being well tolerated with low NRM and high GRFS, while having comparable RI and OS compared to published outcomes of T cell replete MAC UD HCT (Saber et al, 2012). However, the retrospective nature without a comparator is a major limitation which necessitates a future prospective study to validate these findings. [Table: see text]
Intensive chemotherapy in patients with high grade myelodysplastic syndromes (MDS): A systematic review and meta-analysis.
Authors: Benkhadra Raed , Nayfeh Tarek , Bakalov Veli , Hilton Christie , Khan Cyrus , Prokop Larry , Shah Mithun Vinod , Alkhateeb Hassan , Litzow Mark Robert , Murad M. Hassan , Al-Kali Aref
Published: May 2020

e19530

Background: Intensive chemotherapy (IC) regimens are rarely used in patients with myelodysplastic syndromes (MDS) for many reasons including advanced age at diagnosis, the frailty of these patients, the presence of several comorbidities and potentially increased mortality when such regimens are used. Additionally, very little literature exists on its safety and long-term benefit in this population. Aim: To evaluate the safety and effectiveness of IC regimens in patients with MDS. Methods: We searched MEDLINE, Embase, Scopus and Cochrane databases from each database's inception from 1990 to January 27th, 2020. Keywords include: “MDS”, “induction chemotherapy” and “remission induction”. Studies evaluating different IC regimens with MDS were included. IC studies for patients with relapsed/ refractory MDS were excluded. Studies that combined acute myeloid leukemia (AML) and MDS outcomes were excluded. The random-effects model was used to pool relative risks and incidence rates. Main endpoints were overall remission rates (ORR), 30- and 60-days mortality, 1-year, 2-year and 5-year overall survival (OS). Results: Characteristics: From 2001 records, we included 13 studies [1,164 patients, median age 60.1 years (range, 17-88), males 58.9%, 58.4% patients had abnormal cytogenetics, median bone marrow blasts 17.8% (range 4 -29%), 4 studies were randomized]. Induction outcome: IC regimes included “7+3, FLAG, s-HAM, and few other regimens. Response: ORR was 55%, including 52% CR rate. Safety: 30- and 60-days mortality were 7%, 15%, respectively. Survival outcome: median survival was 11.6 months, 1-year, 2-year and 5-year OS were 48%, 21% and 5%, respectively. Randomized studies comparison: adding growth factors to IC did not show statistically significant effects on outcomes regarding induction mortality, ORR and OS (p-value > .05). Conclusions: IC is rarely used in MDS patients and its use is associated with high mortality rates and low long-term survival. Limitations to our studies include the long span of this review over 3 decades and the difficulty of using published studies that combines MDS and AML patients’ outcome. More studies are needed in this population of interest in the future.