bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships among skeletal muscle, symptom burden, health care use, and survival in hospitalized patients with advanced cancer.
Authors: Azoba Chinenye C. , Van Seventer Emily E. , Marquardt Jan Peter , Troschel Amelie S. , Best Till D. , Horick Nora K. , Newcomb Richard , Roeland Eric , Rosenthal Michael Hayden , Bridge Cristopher P. , Greer Joseph A. , El-Jawahri Areej , Temel Jennifer S. , Fintelmann Florian J. , Nipp Ryan David
Published: May 2020

7006

Background: Loss of skeletal muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle density (quality). Hospitalized patients with advanced cancer are a highly symptomatic population at risk for the adverse effects of muscle loss. Thus, we sought to describe associations between muscle mass and density, symptom burden, health care use, and survival in these patients. Methods: We prospectively enrolled hospitalized patients with advanced cancer from 9/2014-4/2017. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire 4 [PHQ4]) symptoms. We used computed tomography (CT) scans performed per routine care ≤45 days prior to enrollment to evaluate muscle mass and density at the level of the third lumbar vertebral body. We categorized patients as sarcopenic using validated sex specific cutoffs. We used regression models to examine associations between muscle mass and density and patients’ symptom burden, health care use, and survival. Results: Of 1,121 patients enrolled, 677 had evaluable CT scan data (mean age = 62.86±12.95 years; 51.1% female). The most common cancer types were gastrointestinal (36.8%) and lung (16.7%) cancer. Most met criteria for sarcopenia (64.0%). Older age and female sex were associated with lower muscle mass (age: B = -0.16, p < .01; female: B = -6.89, p < .01) and density (age: B = -0.33, p < 0.01; female: B = -1.66, p = .01), while higher BMI was associated with higher muscle mass (B = 0.58, p < .01) and lower muscle density (B = -0.61, p < .01). Higher muscle mass was significantly associated with improved survival (HR = 0.97, p < .01), but not with symptom burden or health care use. Higher muscle density was significantly associated with lower ESAS physical (B = -0.17, p = .02), ESAS total (B = -0.29, p < .01), PHQ4 depression (B = -0.03, p < .01) and PHQ4 anxiety (B = -0.03, p < .01) symptoms. Higher muscle density was also associated with decreased hospital length of stay (B = -0.07, p < .01), risk of readmission or death in 90 days (OR = 0.97, p < .01), and improved survival (HR = 0.97, p < .01). Conclusions: Most hospitalized patients with advanced cancer have muscle loss consistent with sarcopenia. We found that muscle mass (quantity) correlated with survival, whereas muscle density (quality) was associated with patients’ symptoms, health care use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address the adverse effects of muscle loss in oncology.
Survival outcomes among older adults (OA) receiving second-line therapy for metastatic CRC (mCRC): 5,289 patients (pts) from the ARCAD Clinical Trials Program.
Authors: McCleary Nadine Jackson , Harmsen William S. , VanCutsem Eric , Sobrero Alberto F. , Goldberg Richard M. , Tabernero Josep , Seymour Matt , Saltz Leonard B. , Giantonio Bruce J. , Dirk Arnold , Rothenberg Mace L. , Koopman Miriam , Schmoll Hans-Joachim , Pitot Henry C. , Hoff Paulo Marcelo , Falcone Alfredo , De Gramont Aimery , Shi Qian
Published: May 2020

7009

Background: Survival outcomes of 2nd line mCRC therapy for OA are poorly understood. We evaluated the rates and survival outcomes of 2nd line therapy among OA age 70+ compared to younger adults (YA) age < 70 following progression on 1st line clinical trials. Methods: Associations between clinical characteristics of pts with available treatment data after progression on 10 of 23 1st line ARCAD trials, time to initial progression (TTiP) and 2nd line therapy were evaluated. Time to progression (TTP) and overall survival (OS) were compared between OA and YA enrolled on 2nd line trials by Cox regression, adjusting for age, sex, ECOG PS, number of metastatic sites, presence of metastasis in lung/liver/peritoneum. Results: Sixteen percent of 1st line ARCAD trial participants were age 70+ (n = 870). Data for 2nd line therapy was available for 60.6% pts (3206/5289). Each additional decade of life was associated with 11% lower odds of receiving 2nd line therapy in multivariate analysis (p = 0.0117). OA participating in 2nd line trials (7.9% age 75+ of 7921) experience similar TTP and OS to YA (mTTP: 5.1 vs. 5.2mos; mOS 11.6 vs 12.4mos, respectively). Conclusions: We did not observe a statistical difference in survival outcomes by age following 2nd line mCRC therapy. Further study is needed to examine unmeasured comorbidity and use of geriatric assessment to select OA likely to benefit from 2nd line therapy. [Table: see text]
Saving the best to the last: Can we wait for second-line?
Authors: Barak Renana , Wolf Ido
Published: May 2020

7013

Background: A common perception of some oncologists is that the vast majority of their patients with metastatic disease will receive 2nd line treatment upon progression. Therefore, “saving” good treatment options for the future may be acceptable. We aimed to examine whether this perception correlates with real-life. Methods: Using an oncology electronic database, consisting of >27,000 patients treated at our institution, we selected consecutive patients with metastatic or locally advanced lung, colon, pancreatic, bile duct and gastric cancers who started standard 1st line, consisting of at least doublet therapy. We then assessed the correlation between proceeding to 2nd line therapy and demographic and clinical variables, including age, gender, initial BMI, hemoglobin, WBC, creatinine, glucose, calcium, as well as survival. Results: A total of 553 patients met the inclusion criteria. Their median age was 66 and 317 were men. Their diagnoses were colon (197), lung (129), pancreas (101), bile duct (71) and gastric (55) cancers. Only 59% received at least one course of 2nd line treatment (61.9% colon, 65.1% lung, 66.3% pancreas, 35.2% bile duct and 54.5% gastric). Probability of reaching 2nd line treatment was associated with disease site (P=0.0002) as well as with age, with patients who received 2nd line being 2.5 years younger compared to those who did not (65 vs. 67.5 years, P=0.008). No other factor, including gender, BMI or standard laboratory values at presentation could predict chances of proceeding to 2nd line, for either the whole group or by primary cancer origin. Survival of patients not starting 2nd line was also significantly shorter across all tumor types. Conclusions: These real-life data indicate that only 60% of patients starting standard doublet or triplet treatment for advanced cancers will commence 2nd line therapy; and this cannot be reliably predicted in advance using standard clinical and laboratory characteristics. Our data challenge the practice of saving good treatment options for subsequent lines, and call for the development of tools enabling prediction of response and tolerance to treatment, pursuing for better patient selection and patient-tailored therapy.
The potential cost-effectiveness of a risk-based pancreatic cancer screening strategy in new-onset diabetes.
Authors: Schwartz Naomi RM , Matrisian Lynn McCormick , Shrader Eva , Feng Ziding , Chari Suresh , Roth Joshua A.
Published: May 2020

7017

Background: There are no established methods for pancreatic cancer (PC) screening, but the National Cancer Institute and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in new-onset diabetes (NOD)—a group with elevated PC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) risk model validation study, we assessed the potential value of CT screening for PC in those determined to be at elevated PC risk, as is being done in a planned PanCAN Early Detection Initiative (EDI) trial. Methods: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of screening those age ≥50 and with NOD for PC using CT imaging vs. no screening. PC prevalence, sensitivity, and specificity were derived from the ENDPAC validation study. PC stage distribution in the no screening strategy and PC survival were derived from SEER. Background mortality for diabetics, screening and cancer care expenditure, and health state utilities were derived from the literature. The base case assumed 40% of screen-detected PC cases were resectable, and a threshold analysis explored the fraction required for screening to be <$100,000 per QALY gained. Life years (LYs), quality-adjusted life years (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2019 USD, and we took a U.S. payer perspective. Results: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $305 in additional expenditure for a cost per QALY gained of $68,059 (Table). Among PC cases, screening resulted in 0.67 more LYs, 0.55 more QALYs, and $22,691 in additional expenditure. In probabilistic analyses, screening resulted in a cost per QALY gained of <$50,000 and <$100,000 in 34% and 99% of simulations, respectively. In the threshold analysis, >25% of screen-detected cases needed to be resectable for the cost per QALY gained with screening to be <$100,000. Conclusions: We found that risk-based pancreatic cancer screening in NOD is likely to be cost-effective in the U.S. if even a modest fraction (>25%) of screen-detected cases are resectable. Future studies should reassess the value of this intervention once PanCAN EDI data become available. [Table: see text]
Project facilitate: A review of the FDA oncology center of excellence expanded access pilot program.
Authors: Kormanik Natasha L , Chan Mitchell , Boehmer Jessica , Kim Tamy , Blumenthal Gideon Michael , Pazdur Richard
Published: May 2020

7023

Background: Expanded Access (EA), also known as “compassionate use,” is a regulatory pathway in which a patient with an immediate life-threatening condition or disease can gain access to an investigational product for treatment when no satisfactory therapy is available. Oncology practices may lack the regulatory experience or administrative support to use EA. In response, FDA OCE launched Project Facilitate (PF), a call center to assist oncology healthcare providers requesting EA. An analysis of single-patient investigational new drugs (IND) was performed to assess the first 10 months of PF compared to the period prior to its launch. Methods: Preliminary data was extracted from the FDA’s central database that yielded 719 single-patient INDs between May 31-November 30, 2018 & 2019 in the Office of Oncologic Diseases (OOD). Data collected included IND receipt date, acknowledgment date, application status, drug name, underlying malignancy of patient, address of requesting physician, withdrawal date, and patient demographics. A manual review of INDs was performed to assess for actual processing dates and to capture demographics not captured by the database. A total of 28 INDs were excluded due to duplications, cancellation by Sponsor prior to issuance of FDA decision, or coding errors in the database. Industry denial explanations were reported by the provider by emails. Results: Data from 692 INDs were analyzed and 692 (100%) were granted safe to proceed. The median processing time was 1 day (mean=2) in 2018 and 1 day (mean= 1.5) in 2019. Our findings indicate that the volume of oncology EA requests increased by 76 (19%) in 2019 vs 2018. A total of 207 unique drugs were requested. Malignancies most frequently involved included: Acute myeloid leukemia (n = 84, 8.3%), soft tissue sarcoma (n = 77, 7.6%), and non-small cell lung cancer (n = 60, 5.9%). States with the highest requests included: California (n = 82, 11.8%), New York (n = 81, 11.7%), and Massachusetts (n = 42, 6.1%). A majority of requests were from major academic centers (77%). All denied requests (N = 9) by industry were due to company’s decision to not provide products outside of a clinical trial. Conclusions: The positive trends in decreased processing times and increased number of requests are consistent with OCE’s mission to improve efficiency of the EA program and ensure equitable access to all oncology patients. [Table: see text]
Breast and cervical cancer screening disparities among transgender patients.
Authors: Oladeru Oluwadamilola Temilade , Ma Sung Jun , Miccio Joseph , Wang Katy , Attwood Kristopher , Singh Anurag K , Haas-Kogan Daphne A. , Neira Paula M
Published: May 2020

7024

Background: Over a million Americans identify themselves as transgender and this population is growing. Transgender status was a pre-existing condition prior to the Affordable Care Act (ACA), and transgender individuals faced unique disparities in gender-specific cancer screening in part due to discrimination in health insurance coverage. Modern literature for transgender adults’ adherence to cancer screening is limited. To fill this knowledge gap, we conducted a cross sectional study to investigate transgender individuals’ self-reported adherence to cancer screening and access to primary care compared to cisgender individuals. Methods: The Behavioral Risk Factor Surveillance System database was queried for transgender (either male-to-female [MTF] or female-to-male [FTM]) and cisgender adults from 2014-2016 and 2018. Primary endpoints were adherence to breast and cervical cancer screening guidelines and access to primary health care. Those with prior hysterectomy, breast and cervical cancer were excluded. Multivariable logistic regression was performed to evaluate the association of transgender status with cancer screening and healthcare access, after adjusting for demographic characteristics and survey weights. Results: A total of 219,665 and 206,446 participants were eligible for breast and cervical cancer screening, respectively. Of those, 614 (0.28%) and 587 (0.29%) transgender participants were eligible for each cancer screening type, respectively, representing a weighted estimate of nearly 200,000 transgender participants total. When compared to cisgender counterparts, transgender participants were less likely to adhere to breast cancer screening (FTM: OR 0.47, p < 0.001; MTF: OR 0.04, p < 0.001) and to have received any breast cancer screening (FTM: OR 0.32, p < 0.001; MTF: OR 0.02, p < 0.001). Similarly, FTM participants were less likely to adhere to cervical cancer screening (OR 0.42, p < 0.001) and to have received any cervical cancer screening (OR 0.26, p < 0.001). In addition, transgender participants were more likely to have no primary care physician (FTM: OR 0.79, p < 0.001; MTF: OR 0.58, p < 0.001) and to be unable to see a physician when needed within the past year due to medical cost (FTM: OR 1.44, p < 0.001; MTF: OR 1.36, p < 0.001). Conclusions: Despite the implementation of the ACA, limited primary care access and poor adherence to breast and cervical cancer screening are evident for transgender populations. Further research efforts to improve the utilization of preventive cancer services are needed for this underserved population.
Global oncology authorship and access patterns.
Authors: Bourlon Maria Teresa , Jimenez Brenda , Matar Charbel Fadi , Gunn Emilie M. , Ginsburg Ophira M. , Lopes Gilberto , Segelov Eva
Published: May 2020

7061

Background: Global Oncology is a movement to improve equitable access to cancer control and care, recognizing challenges due to economic and social factors between high, middle, and low-income countries (HIC, MIC, LIC). Access to local, regional, and global cancer data and analysis is a major driver for building a global oncology community. The JCO Global Oncology (JCO GO) online open access journal was established in 2015 with the mission to be the voice of research relevant to populations with limited resources. To assess its goals of encouraging global interaction and increasing MIC and LIC engagement, we analyzed authorship and accessing data. Methods: Logged views of articles published in 2018 were identified by DOI, using Google Analytics during the period 01/01/2018 to 06/30/2019. The country of origin of all authors and the location of downloads were classified according to the 218 economies listed in The World Bank Data (WBC) of 2019. Results: 132 articles were published in JCO GO in 2018 with 88152 views, from which the accessing nation was identified for 99%. Views originated from 180 countries: 35% HIC, 51% MIC, and 14% LIC. The most common accessing countries were: USA (37%), India (14%), United Kingdom (3%), Brazil (3%), and Ethiopia (3%). Corresponding authors came from 34 nations: 60% HIC, 32% MIC, and 8% LIC. The most common economies involved in any authorship were: USA (47%), India (10%), Brazil (5%), Mexico (4%), and Nigeria (3%). Reader origin did not differ according to corresponding author WBC. Article authorship was exclusively from one economic category in 49%: 23% HIC 16% MIC, 2% LIC. For 59% of articles, authorship came from mixed economies: 42% HIC + MIC, 11% HIC + LIC, 0% MIC + LIC, 6% HIC + MIC + LIC. Conclusions: JCO GO ’s reach extends to over 80% of the world´s economies. The majority of articles have authors from mixed WBC countries. Areas identified to address are: low level of LIC corresponding authorship; few papers from authors across all economies; no papers from only LMICs authors; low percentage of views by LIC. This information provides focus for global oncology authorities to target interventions to reduce the academic segregation of LICs, such as global oncology funding opportunities, mentorship and policies to encourage interactions and develop MIC and LIC leaders.
Vital status ascertainment in cancerlinq discovery (CLQD): Improvement in mortality capture with a supplemental data source.
Authors: Potter Danielle , Kaltenbaugh Melinda , Kabadi Shaum , Taylor Aliki , Pascual Esther , Koskimaki Jacob , Brothers Raven , Stoeber Philip , Mena Jose , Garrett-Mayer Elizabeth
Published: May 2020

7064

Background: Overall survival (OS) is the gold standard outcome in clinical cancer research but many clinical trials cannot assess long-term OS. Real-world data sources can be used to calculate long-term OS, but only if vital status is accurately captured. Methods: The primary goal was to assess concordance of death dates from CLQD and an external source, and the effect of incorporation of external death data on estimates of OS. CLQD obtains electronic medical record (EMR) data from participating US oncology sites. Under-reporting of vital status is a common problem with EMR data; we investigated the value of including death data from a commercially available database, obituarydata.com (OBD) into CLQD. OBD pulls death data from published obituaries across the US. A matching algorithm is used to match patients in CLQD and OBD. OBD death data from breast, lung, ovarian, and pancreatic cancer patients diagnosed between 2010–2018 supplemented the CLQD in this study. OS was calculated using Kaplan-Meier estimation; Pearson correlation was used for comparing time to death. Results: The addition of OBD modestly changes OS estimates (see Table). Among a subset of patients with death dates in both CQLD and OBD, dates were highly correlated for breast (r = 0.98), lung (r = 0.93), ovarian (r = 0.99), and pancreatic (r = 0.88) cancers. When date differences existed, they were ≤10 days for > 95% of the patients. These results suggest death dates are reliable in CLQD EMRs. OS curves were as expected, with OS decreasing by stage and age at diagnosis. Conclusions: Incorporating OBD modestly improves OS estimates and shows that when death data is present in CLQD, it is reliable. Future enhancements will focus on improving sensitivity of mortality ascertainment with external data linkages, without compromising specificity. [Table: see text]
Three versus six months of adjuvant chemotherapy for colorectal cancer: A multi-country cost-effectiveness and budget impact analysis.
Authors: Hanna Catherine , Robles-Zurita Jose Antonio , Jones Robert J. , Boyd Kathleen
Published: May 2020

7076

Background: The international Short Course Oncology Treatment (SCOT) trial demonstrated non-inferiority and significantly less toxicity of 3 versus 6 months of adjuvant chemotherapy for patients with colorectal cancer (CRC). This study assesses the value of shorter treatment and the economic implications of implementing the findings from the perspective of the countries that participated in the SCOT trial. Methods: Individual patient level data (n=6055) from the SCOT trial was used in a fully-pooled, cost utility analysis for the six participating countries. The incremental net monetary benefit (INMB) per patient was calculated using a willingness to pay threshold of one Gross Domestic Product per capita for each country. Responses to a clinician questionnaire (n=265 across 21 countries collected in April 2019) were used to estimate extent of practice change. The budget impact over 5 years of using shorter treatment was calculated, using 2019 and US dollars (USD) as the base year and currency, respectively. Results: Cost drivers for differences between the SCOT trial arms were reduced chemotherapy costs and fewer hospitalisations in the first treatment year. The INMB per patient of using shorter treatment and subsequent monetary impact on healthcare provider budgets resulting from implementation are shown in Table. This is a cost saving treatment strategy in all countries. The budget impact over 5 years amounts to savings of nearly half a billion USD. Conclusions: The economic burden of CRC treatment globally exceeds $39 billion per annum. Understanding the costs and consequences of widespread clinical practice change is important for optimal budget planning. This study has widened the transferability of results from a phase III cancer trial, showing shorter treatment is cost-effective from a multi-country perspective. The vast savings could provide benefit elsewhere within a limited healthcare budget, and justify the investment in conducting the SCOT trial. [Table: see text]
Total cost of lung cancer care associated with broad panel versus narrow panel sequencing.
Authors: Brito Rogelio Alberto , Cullum Bob , Hastings Kevin , Avalos-Reyes Elisea , Karos Rebecca , Johnson Kjel Andrew
Published: May 2020

7077

Background: Many lung cancer patients are diagnosed late with advanced or metastatic disease. Targeted therapies can improve quality of life and increase the chances of progression-free survival versus conventional treatments. An understanding that there may be more than one driver mutation associated with a specific lung tumor is crucial for the timing and delivery of the most effective line of therapy. Broad panel sequencing (BPS) minimizes tissue use and enables personalized treatment that decreases the use of ineffective agents and unwarranted side effects, in addition to opening pathways to early clinical trials. However, many payors do not reimburse for BPS. The objective of this study was to determine if BPS leads to lower total cost of care versus narrow panel sequencing (NPS). Methods: We identified new lung cancer patients who completed BPS (Current Procedural Terminology (CPT) code 81455, 51+ genomic test) or NPS (CPT code 81445, 5-50 genomic test) using medical claims from January 1, 2018, to March 31, 2019. We defined total cost of care as allowed costs paid for medical and pharmacy claims across a six-month time period from the first gene sequencing panel. We also compared the allowed costs of BPS and NPS. A Student’s t-test was used to compare differences and results are presented as mean +/- standard deviation. Results: From January 2018 to March 2019, we identified 45 patients who underwent BPS sequencing and 399 patients who underwent NPS. The average BPS cost was $1,977 +/- $2,713 versus the average NPS lab cost $719 +/- $1,087, p < 0.0001. The average 6-month per member per month (PMPM) total cost was $11,535 +/- $9,168 among those who underwent BPS compared to $20,039 +/-19,642 in those who underwent NPS. This difference of $8,504 was statistically significant, p = 0.0022. Conclusions: BPS has been shown to optimize treatments in patients with lung cancer. These initial results of claims suggest that while lung cancer patients undergoing BPS have higher total sequencing costs than those undergoing NPS, BPS significantly reduces overall total cost of lung cancer care. Identifying the broader genomic landscape of a patient’s tumor earlier will empower oncology providers and lung cancer patients with information to make timely, precise treatment decisions that are ultimately more cost effective.
Patient-reported benefit from proposed interventions to reduce financial hardship during cancer treatment.
Authors: Aviki Emeline , Chino Fumiko , Ramirez Julia , Blinder Victoria Susana , Mueller Jennifer Jean , Leitao Mario M. , Abu-Rustum Nadeem , Gany Francesca
Published: May 2020

7080

Background: Awareness of cancer patients’ financial toxicity (FT) has increased substantially over the past decade; however, interventions to minimize financial burden remain underdeveloped and understudied. This survey-based study explores patient beliefs on which potential mitigating strategies could improve their financial hardship during cancer treatment. Methods: Interviewer-administered surveys were conducted with consecutive patients in an outpatient, urban, private academic Gynecologic Cancer clinic waiting room for 2 weeks in August 2019. The survey items included patient demographics, disease characteristics, the Comprehensive Score for Financial Toxicity (COST) tool (validated measure of FT with score 0-44; lower scores indicate worse FT), assessment of cost-coping strategies, and patient-reported anticipated benefit from described potential interventions (items that were feasible and relevant to implement in clinic). Results: Of 101 patients who initiated the survey, 87 (86%) completed it and were included in this analysis. The median age was 66 (range, 32-87). Thirty-eight patients (44%) had ovarian, 29 (33%) uterine, 5 (6%) cervical, and 15 (17%) an “other” gynecologic cancer. The median COST score was 32 (range, 6-44). Twenty-nine patients (33%) had COST scores ≤25 and 16 (18%) had COST scores ≤18. The most frequent cost-coping strategy reported was reducing leisure activities (n = 36, 41%) and using savings to pay for medical bills (n = 34, 39%). Six patients (7%) reported not taking a prescribed medication in the past 12 months due to the inability to pay and 0 reported skipping a recommended imaging study. When it came to interventions patients anticipated would improve their current financial hardships, 34 (39%) indicated access to transportation assistance to and from appointments, 31 (36%) said “knowing up front how much I’m going to have to pay for my healthcare”, 29 (33%) indicated “minimizing wait time associated with appointments, which keeps me away from work”, and 22 (25%) indicated “access to free food during/around appointments and treatments”. Only 26 (30%) noted they were not experiencing financial hardship. Conclusions: For an outpatient population of gynecologic cancer patients, several focused, feasible interventions could be implemented to potentially decrease patient FT. Our study can help health care providers in the design of interventions to create meaningful improvements in patient financial burden. Next steps should assess the impact of targeted interventions on patient outcomes.
Financial burden of discarded weight-based cancer drugs to payers and patients in private insurance market.
Authors: Shih Ya-Chen T. , Xu Ying , Zhao Hui , Yao James C.
Published: May 2020

7083

Background: Studies assessing wastage of discarded weight (WT)-based cancer drugs (can-RX) derived their estimates from Medicare Average Sales Prices + 6% mark-up. With higher mark-ups, financial impact of discarded can-RX can be much higher in private insurance market. In addition, no study has examined the financial burden for patients(pts) even though they are subject to out-of-pocket payment (OOP) of the discarded RX. This study fills in these important knowledge gaps. Methods: We obtained the list of WT-based can-RX from the 2017 Centers for Medicare and Medicaid Services Part B Discarded Drug Units Report and gathered information on package size and recommended dose from IBM Micromedex. We identified pts who received WT-based can-RX from 2017 MarketScan data and linked to MarketScan Health Risk Assessment to obtain WT and height for a subset of pts. For each claim, we derived the recommended dose based on pt’s RX and his/her WT or body surface area (calculated from WT and height) and estimated the % of discarded dose. We quantified OOP as the sum of deductible, copayment, and coinsurance, and classified pts’ insurance by their enrollment to high-deductible (HD) plans. For claim-level analysis, we applied beta regression (for fractional outcomes) to determine factors associated with % discarded while accounting for within pts correlations. Covariates were age group (grp) ( < 50, 50-59, > = 60), WT grp ( < 150, 150-199, > = 200lb), HD plan (yes/no), region, cancer type, and can-RX. For pt-level analysis, we calculated the amount payers and pts spent on all and discarded can-RX in 2017 and compared OOP b/t pts in HD and non-HD plans. Results: Of 27,883 claims of WT-based can-RX, the median discarded % was 0.10 (mean 0.19, SD = 0.21). In addition to can-RX and cancer type, significantly higher discarded % was found in the lowest WT grp (0.03, P < 0.001, vs. WT > = 200lb) and significantly lower % was found in the middle age grp (-0.01, P = 0.02 vs. age < 50). Of 1963 pts, 778 (40%) had HD plans. Payments by payers (NETPAY) and pts (OOP) for total and discarded can-RX and the comparison b/t HD and non-HD plans are shown in Table. Conclusions: Payers incurred substantial financial burden from discarded can-RX. While OOP costs were modest for most privately insured pts, 5.3% of pts (~8% in HD plans) paid > $400 for discarded RX. [Table: see text]
Cost implications of clinical trial (CT) participation in metastatic non-small cell lung cancer (NSCLC).
Authors: Merkhofer Cristina , Chennupati Shasank , Sun Qin , Eaton Keith D. , Martins Renato G. , Ramsey Scott David , Goulart Bernardo H. L.
Published: May 2020

7084

Background: To assess the value of CTs in advanced NSCLC from the payer perspective, we compared insurance-related total direct medical costs for NSCLC patients who enrolled in CTs vs. those who did not. Methods: After linking electronic health records with tumor registry and claims data, we identified 101 patients with metastatic NSCLC diagnosed between 1/1/2007 and 12/31/2015 and treated at the Seattle Cancer Care Alliance. Eligibility criteria included 60-day minimum survival, claims for ≥ 1 anti-cancer drug within 180 days of diagnosis and insurance enrollment for the first 12 months after diagnosis. We abstracted patient sociodemographic, disease and treatment data, and obtained death dates from the Washington State Cancer Registry, censoring patients alive on 3/7/2019.We used the Kaplan-Meier sample-average (KMSA) estimator with bootstrapped 95% confidence intervals to describe direct medical costs and compared costs in CT enrollees vs. non-enrollees by applying a generalized linear model (Gamma distribution, log link) adjusted for confounding covariates. Results: Of 101 patients, 39 (39%) enrolled in CTs. Compared with non-enrollees, CT enrollees were younger (mean age 61.6 vs. 66.5 years), female (67% vs. 47%), Asian (18% vs. 11%), never smokers (41% vs.32%), had commercial insurance (44% vs. 35%), resided in metropolitan areas (90% vs. 79%) and had a higher median income ($81,149 vs. $76,844). Table shows KMSA estimates of total direct medical costs and adjusted mean lifetime total direct medical costs by CT participation. After adjusting for sex, smoking status, residence, income, insurance payer, ECOG and mutation status, CT enrollment was associated with an increase in lifetime total direct medical costs compared with no enrollment (adjusted cost ratio=1.39; 95% CI: 1.01, 1.90; p=0.043). Conclusions: CT participation is associated with increased total direct medical costs in patients with metastatic NSCLC. Our results may inform partnerships between trial sponsors, oncology centers and payers to sustain treatment innovation through CTs. [Table: see text]
Phase II study of pevonedistat (P) + azacitidine (A) versus A in patients (pts) with higher-risk myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML), or low-blast acute myelogenous leukemia (LB AML) (NCT02610777).
Authors: Ades Lionel , Watts Justin M. , Radinoff Atanas , Arnan Montserrat , Cerrano Marco , Font Lopez Patricia , Zeidner Joshua F. , Diez-Campelo Maria , Graux Carlos , Liesveld Jane , Selleslag Dominik , Tzvetkov Nikolay , Fram Robert J. , Zhao Dan , Faller Douglas V. , Sekeres Mikkael A.
Published: May 2020

7506

Background: P, the first and only small-molecule inhibitor of the NEDD8-activating enzyme, disrupts proteasomal degradation of select proteins and has shown promising clinical activity and good tolerability in combination with A in AML. Methods: 120 pts with higher-risk (Revised International Prognostic Scoring System risk > 3) MDS/CMML or LB AML naïve to hypomethylating agents were randomized 1:1 to receive P 20 mg/m2 intravenously (IV) on days (d) 1, 3, 5 + A 75 mg/m2 (IV/subcutaneously) on d 1–5, 8, 9 (n = 58), or A alone (n = 62), in 28-d cycles until unacceptable toxicity, relapse, transformation to AML, or progression. The primary endpoint was overall survival (OS), although the study was underpowered for OS. Results: Baseline characteristics were generally balanced between arms. Pts received a median of 13.0 vs 8.5 cycles of P+A vs A. Median OS in the intent-to-treat (ITT) population with P+A vs A (n = 120) was 21.8 vs 19.0 mos (hazard ratio [HR] 0.80; 95% CI 0.51–1.26; P = .334; median follow-up 21.4 vs 19.0 mos). Subanalyses showed median OS with P+A vs A in higher-risk MDS (n = 67) of 23.9 vs 19.1 mos (HR 0.70; 95% CI 0.39–1.27; P = .240) and in LB AML (n = 36) of 23.6 vs 16.0 mos; HR 0.49; 95% CI 0.22–1.11; P = .081). Event-free survival (EFS – time from randomization to death/transformation to AML) with P+A vs A trended longer in the ITT population (median 21.0 vs 16.6 mos; HR 0.65; 95% CI 0.41–1.02; P = .060) and was significantly longer in higher-risk MDS (median 20.2 vs 14.8 mos; HR 0.54; 95% CI 0.29–1.00; P = .045). In response-evaluable pts, overall response rate was 71% (n = 39/55; 46% complete remission [CR] + CR with incomplete blood count recovery [CRi], 5% partial response [PR], 20% hematologic improvement [HI]) with P+A vs 60% (n = 32/53; 38% CR+CRi, 8% PR, 15% HI) with A. In higher-risk MDS, CR rate was 52% vs 27% ( P = .050) with P+A vs A. Median A dose intensity was 97% vs 98% with P+A vs A. Rates of grade ≥3 adverse events were 90% vs 87% with P+A vs A; the most common were 31% vs 27% neutropenia, 26% vs 29% febrile neutropenia, 19% vs 27% anemia, and 19% vs 23% thrombocytopenia. On-study deaths occurred in 9% of P+A pts and 16% of A pts. Conclusions: P+A had a comparable safety profile to A alone, did not increase myelosuppression, and maintained A dose intensity. Although not statistically significant, P+A increased OS, EFS, and response rates vs A, particularly in pts with higher-risk MDS. Further evaluation of P+A vs A is ongoing in a randomized phase. Clinical trial information: NCT02610777 .
Inotuzumab ozogamicin (INO) plus bosutinib (BOS) in R/R PH+ ALL or CML in lymphoid blast phase (CML LBP).
Authors: Jain Nitin , Maiti Abhishek , Ravandi Farhad , Konopleva Marina , Alvarado Yesid , Kadia Tapan M. , Short Nicholas James , Borthakur Gautam , Naqvi Kiran , Pemmaraju Naveen , Dinardo Courtney Denton , Daver Naval Guastad , Yilmaz Musa , Patel Keyur P. , Linderman Debra B , Garris Rebecca , Jabbour Elias , Cortes Jorge E. , Kantarjian Hagop M.
Published: May 2020

7512

Background: Pts with R/R Ph+ ALL and CML LBP have poor outcomes. INO is an anti-CD22 antibody drug conjugate approved for R/R ALL. BOS is a 2nd generation BCR-ABL TKI approved for CML. Methods: This was a phase I/II study of INO + BOS for R/R Ph+ ALL and CML LBP. Primary objective was to determine safety and the maximum tolerated dose (MTD) of the combination. Secondary objective was to assess efficacy. Pts with T315I mutation were excluded. Pts needed to have adequate organ function (Cr ≤2 gm/dL, total bilirubin ≤2 mg/dL, ALT & AST ≤3xULN). BOS was dosed once daily starting on cycle 1 day 1, and 3 dose levels were evaluated (300, 400, 500 mg) in a standard 3+3 design. INO was given IV weekly during cycle 1 (0.8 mg/m2 day 1; 0.5 mg/m2 day 8; 0.5 mg/m2 day 15). In responding pts, INO was subsequently administered at 1 mg/m2 once every 4 weeks for a total of 6 cycles. Results: Between June 2015 and December 2019 we enrolled 18 R/R pts (16 Ph+ ALL, 2 CML LBP). The median age was 62 yrs (range 19-74), median no. of prior therapies was 1 (range 1-5) and 9 pts had ABL kinase domain mutations at screening. There were no early deaths (<30 days). 3 pts were treated at BOS dose level 1; 6 pts at dose level 2; 9 pts at dose level 3. 1 pt had a DLT at dose level 2 - G3 skin rash, and 2 pts had a DLT at dose level 3 - both G3 skin rash. First 3 pts at dose level 3 did not receive ≥80% BOS doses during cycle 1 due to issues unrelated to adverse events (AE). As 2/6 DLT evaluable pts at dose level 3 had DLTs thus exceeding the MTD, the dose level 2 was identified as the MTD. Most frequent AE were diarrhea in 50%, rash in 50%, and nausea in 39%. Grade 3 AEs were rash (3), reversible ALT elevation (1) and hyponatremia (1). No pts had veno-occlusive disease. Pts have received a median of 3 cycles (range 1-8) with a median of 1 cycle to response (range 1-2). Responses are shown in Table. Median time to response was 1 months (mo, range 0.8-2.1), median time to negative MRD by flow cytometry (FCM) was 6.9 mo (range 3.4-18) and median time to complete molecular response (CMR) was 9.1 mo (range 3.4-18). After a median follow-up of 32 mo, the median overall survival was 15.4 mo and median event-free survival censored at stem-cell transplantation (SCT) was 6.1 mo. 6 pts underwent SCT, 8 pts relapsed, 10 pts are alive and 2 pts continue therapy. Conclusions: INO + BOS was well tolerated and showed promising activity in R/R Ph+ ALL and CML LBP. Clinical trial information: NCT02311998 . [Table: see text]
Long-term survivors and gilteritinib safety beyond one year in FLT3-mutated R/R AML: ADMIRAL trial follow-up.
Authors: Perl Alexander E. , Martinelli Giovanni , Neubauer Andreas , Berman Ellin , Baer Maria R. , Larson Richard A. , Fathi Amir Tahmasb , Yokoyama Hisayuki , Hosono Naoko , Hasabou Nahla , Lu Qiaoyang , Bahceci Erkut
Published: May 2020

7514

Background: The phase 3 ADMIRAL trial showed that gilteritinib was superior to salvage chemotherapy (SC; median overall survival [OS]: 9.3 vs 5.6 mo, respectively) in FLT3mut+ R/R AML patients (pts; Perl, et al. N Engl J Med. 2019). This follow up (FU) of the ADMIRAL trial assessed long-term (LT) survivors and gilteritinib safety beyond 1 year. Methods: A data cut was performed 1 year after the primary analysis. Response outcomes in LT survivors (OS ≥18 mo) in the gilteritinib arm, and safety during and after 12 mo of gilteritinib therapy were assessed. Results: At 1 year after the primary analysis, median FU for OS was 29.2 mo. Median OS remained longer with gilteritinib (9.3 mo) than with SC (5.6 mo; HR=0.679 [95% CI: 0.527, 0.875], nominal P=0.0026); 18-mo OS rates were 27% and 15%, respectively (Table). Of 49 censored pts in the gilteritinib arm, 20 continued treatment; 13 of these 20 pts underwent transplantation (HSCT) and received gilteritinib post-HSCT. Median gilteritinib exposure was 4.1 mo (IQR, 2.1-8.2) and median average dose was 120 mg/day (range, 43.8-192.3); 12% (n=30/246) of pts had ≥18 mo and 7% (n=17/246) had ≥24 mo of drug exposure. A total of 63 gilteritinib-treated pts had OS ≥18 mo (median exposure, 17.6 mo [IQR, 3.1-25.7 mo]). A high proportion of these LT survivors achieved remission pre-HSCT (Table); median durations of complete remission (CR) or CR with partial hematologic recovery (CRh) have not been reached. After a median of 3.5 mo, 35 of 63 (56%) LT survivors underwent HSCT; 25 of these 35 pts (71%) received post-HSCT gilteritinib therapy. Of 28 pts who did not undergo HSCT, 15 (54%) received gilteritinib for ≥18 mo. Most common grade ≥3 adverse events (AEs) during the first 12 mo of gilteritinib therapy were febrile neutropenia (45%), anemia (40%), and thrombocytopenia (23%); rates of these grade ≥3 AEs decreased to 8%, 10%, and 0, respectively, after 12 mo of treatment. Most common fatal AEs during the first 12 mo of gilteritinib therapy were AML (11%), infections (11%), and cardiac disorders (3%); after 12 mo of treatment, rates of these fatal AEs were 6%, 8%, and 2%, respectively. Conclusions: Results from this ADMIRAL trial FU suggest LT survival in pts receiving gilteritinib is related to ongoing remission, subsequent HSCT, or post-HSCT gilteritinib therapy. The safety profile of gilteritinib beyond 1 year was stable. Clinical trial information: NCT02421939 . [Table: see text]
Clonal hematopoiesis in the bone marrow and blood of healthy volunteers.
Authors: Hirsch Pierre , Ravalet Noémie , Guermouche Helene , Gallay Nathalie , Gyan Emmanuel , Delhommeau François , Herault Olivier
Published: May 2020

7517

Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been described in blood samples from large series of patients. Its prevalence and consequences remain questioned because sequencing methods vary and because most studies were performed in cohorts of individuals suffering from non-hematological diseases (solid cancers, diabetes, cardiovascular or psychiatric diseases). CHIP has been described as a risk factor for blood cancer. However, the diagnosis of most blood cancers relies on morphologic and genetic examination of the bone marrow, and clonal hematopoiesis has never been evaluated in bone marrow samples from healthy individuals. Hence, it is not clear whether the current definition of CHIP is clinically relevant. To address this issue, we studied clonal hematopoiesis in paired peripheral blood and bone marrow samples from an unprecedented cohort of rigorously selected healthy volunteers. Methods: Here, we investigated the frequency of clonal hematopoiesis in 82 paired bone marrow and blood samples from carefully selected healthy adult volunteers (HEALTHOX clinical trial, ClinicalTrials.gov Identifier: NCT02789839). This study was approved by the ethics committees (CPP Tours and AFSSAPS identifier ID-RCB: 2011-A00262-39; CPP Ile-de-France III: 2753). Forty-one genes known to be mutated in myeloid malignancies were sequenced with a 1% threshold of detection. All variants were checked using IGV software v2.3. Statistical analyses were performed using Mann-Whitney, chi-squared, Fisher’s exact, Wilcoxon matched-pairs tests or Spearman correlation using GraphPad Prism 6. Results: In bone marrow samples, clones were found in almost 40 % of healthy volunteers over 50 years-old (yo). The most frequent mutations were found in DNMT3A (48%) and TET2 (28%) and the other mutations were found in ASXL1 (8%), JAK2 (8%), RAD21 (4%) and SRSF2 (4%) with one individual carrying three variants. Blood parameters and bone marrow smears were normal with the exception of two individuals with mild macrocytosis or thrombocytosis. Clonal hematopoiesis cases differed from others by age (62.8 vs. 38.6 years, P < .0001) and platelet count (294 vs. 241 G/L, P < .0208). Conclusions: These results confirm that clonal hematopoiesis is a very common condition in healthy adults over 50 years old. Consequently, the detection of driver myeloid mutations should be interpreted with caution in the absence of cytologic abnormalities in the blood and/or in the bone marrow.
A fork in the road: A mixed methods study exploring why older adults with acute myeloid leukemia choose different treatment paths.
Authors: LeBlanc Thomas William , Walter Roland B. , Hernandez Loriana , Morgan Lucy , Bell Timothy , Panter Charlotte , Peloquin Francois , Healy Jasmine , Gater Adam , Welch Verna , Amer Karim , O'Hara Louise , Hohman Ryan , Brown Andrew , Russell Nigel , Merino Diana M. , Horikoshi Neil , Maze Dawn
Published: May 2020

7520

Background: Current treatment options for acute myeloid leukemia (AML) are diverse, including intensive chemotherapy (IC), low intensity therapy, best supportive care (BSC), and hospice care. Despite continued development of new therapies, recent data suggest that approximately 60% of older US patients remain untreated, but reasons for this are not well understood. By gathering insights from physicians, patients, and their family members, this study aims to better understand the factors that influence treatment decisions for adults with AML. Methods: Physicians in the US (n=4), UK (n=3) and Canada (n=3), and 15 US AML patient-family member dyads took part in one-on-one, 60-minute semi-structured interviews. Each participant rated a series of factors on a scale from 0 (not at all important) to 3 (very important) to determine their importance in treatment decision-making. Among the 15 adults with AML (>65 years, not taking IC) interviewed thus far, 13 had not received any treatment. Additional interviews are scheduled in the UK and Canada with patients having varied treatment experiences (data will be available for presentation). Results: To date, findings highlight the key role perceptions of side effects and patient health play in treatment decision making. A fear of treatment side effects was the primary reason patients (n=9/13) opted not to receive treatment. For the 2/15 study patients who had received treatment, side effects were considered the worst part of their treatment experience. Physicians also stated patients on BSC would be more willing to take low intensity treatments if risks (e.g., side effects) were minimized. Patients (n=11/15), their family members (n=11/15), and physicians (n=10/10) agreed that patients’ health (including age and comorbidities) influenced if treatment was pursued. Additionally, US physicians suggested that some patients have little desire to pursue treatment, with patients’ perception of low intensity therapy having poor efficacy and proximity of care influencing their choice for BSC or hospice care. Further analysis will explore other factors influencing patients’ treatment decisions and differences among patients who receive treatment versus those who do not. Conclusions: The treatment decision-making process for older adults with AML is complex and multifactorial. Understanding factors that influence treatment decisions is important if drug developers and prescribers are to ensure the availability of therapies that better align with individual patients’ needs.