bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of insurance status on treatment for stage 0-IV breast cancer.
Authors: Greenup Rachel Adams , Thomas Samantha Marie , Fayanju Oluwadamilola Motunrayo , Hyslop Terry , Hwang Eun-Sil Shelley
Published: September 2018

6532

Background: Health insurance can influence utilization of cancer care. We sought to determine whether insurance status impacts treatment patterns and survival in women with stage 0-IV breast cancer. Methods: Women ages 18-69 years old, diagnosed with unilateral stage 0-IV breast cancer between 2004 and 2014 were selected from the National Cancer Data Base. Insurance status was categorized as Private, Medicare (65+ yo), Medicare (18-64 yo), Medicaid, or Uninsured. After adjustment for known covariates, generalized and binary logistic regression were used to estimate the association of insurance type with receipt of treatment. A multivariate Cox proportional hazards model was used to estimate the association of insurance status with overall survival. Results: A total of 610,450 women met inclusion criteria. Median age was 56 (48-63). Insurance status included: 72.1% Privately insured, 13.9% Medicare 65+, 4.8% Medicare 18-64, 7.1% Medicaid, and 2.1% Uninsured. Women with private insurance were more likely to present with stage 1 breast cancer, and less likely to present with stage 4 disease when compared to Medicaid or Uninsured patients (stage 1: 63.4%, 49.4%, 48.2%, p < 0.01; stage IV: 0.8%, 1.8%, 2.1%, p < 0.01). Risk of death was higher in uninsured or Medicaid patients when compared to those with private insurance (HR 1.52, 95% CI 1.41-1.64; HR 1.6, 95% CI 1.52-1.68). Receipt of chemotherapy and radiation did not differ between Medicaid, Uninsured, or Privately insured patients, but women without private insurance were more likely to receive neoadjuvant chemotherapy (OR 1.14, 95% CI 1.09-1.19; OR 1.16, 95% CI 1.07-1.25, respectively, p < 0.01). Uninsured women were more likely to undergo mastectomy without reconstruction (OR 1.57, 95% CI 1.49-1.65), and less likely to undergo unilateral or bilateral mastectomy with reconstruction than lumpectomy and radiation (OR 0.57, 95% CI 0.53-0.61; OR 0.35, 95% CI 0.32-0.39). Conclusions: Stage at diagnosis and risk of death were higher in Medicaid and uninsured breast cancer patients when compared to those with private insurance. Insurance status did not predict differences in receipt of surgery, chemotherapy, or radiation but did affect oncologic outcomes.
Does access to cancer drugs relate to survival benefit? A European study in countries with different economic status.
Authors: Wilking Nils Erik , Jönsson Bengt , Lindgren Peter , Wilking Ulla
Published: September 2018

6535

Background: As new cancer drugs come at a high cost, it is of interest to examine if drugs with high impact on survival has a relative higher uptake compared to drugs with limited impact on survival in countries with limited resources (low Gross National Product; GDP/capita) versus countries with better resources (medium or high GDP/capita). Methods: Based on published clinical trial data, including ESMO- and ASCO value scales, we selected three drugs with high impact on survival and their main indications; imatinib/Chronic Myeloid Leukemia (CML), rituximab (some use outside oncology)/lymphoma and trastuzumab/breast cancer compared to everolimus/ renal cancer, sorafenib/renal cancer and bevacizumab/colorectal cancer as drugs with limited impact on survival. Countries in Europe were divided into three economic groups: upper-tier GDP/ capita 36,000 – 73,400 €; (Austria, Belgium, Denmark, Finland, Ireland, The Netherlands, Norway, Sweden, Switzerland); mid-tier GDP 22,800 – 35,400 €; (France, Germany, Italy, Spain, UK) low-tier GDP 5,800 – 18,100 € (Bulgaria, Croatia, Czech Republic, Greece, Hungary, Poland, Portugal, Romania, Slovakia, Slovenia). Sales data from IMS Health and epidemiological data from IARC Cancer Mondial, (WHO) were used. Access to drugs was measured as use in g/case (defined as cancer mortality in 2012) and includes total usage from introduction until end of 2014. Access in the upper-tier country group was set as 100% usage. Results: As seen in the table, access in mid-tier countries was 64-76% and low-tier countries 34-55% respectively for drugs with higher survival impact and access in mid-tier countries was 73-105% and low-tier countries 34-59% respectively, for drugs with lower survival impact. More detailed data on access in individual countries within each GDP/capita group will also be presented. Conclusions: Proven survival benefit did not affect spending on costly cancer drugs in countries with lower GDP. [Table: see text]
Comparison between Canadian and British oncology drug review recommendations and their impact on patient access.
Authors: Smith Matthew K. , Khan Omar Farooq , Yip Steven , Tang Patricia A.
Published: September 2018

6537

Background: Access and funding for oncology medications in Canada and the United Kingdom are influenced by recommendations released by the pan-Canadian Oncology Drug Review (pCODR) and the National Institute for Health and Care Excellence (NICE), respectively. This study investigated variations between these organizations’ recommendations and the clinical implications these differences had on access to medications. Methods: The pCODR Drug Review and NICE Technology Appraisal Guidance databases were reviewed to identify all oncological drug recommendations made by both agencies between 2008 and 2016. Recommendations were matched and then evaluated according to an algorithm to identify clinically relevant differences that restricted access in one jurisdiction relative to the other. Length of time from drug submission to final recommendation by NICE and pCODR were compared using Wilcoxon rank sum tests, as was the length of time between regional funding approval. Results: Between 2008 and 2016, 31 medication indications were evaluated by both pCODR and NICE. For 12 indications, funding was only supported by one agency. Eight indications were approved by both agencies, but with clinically relevant differences in wording, with each agency making a more restrictive recommendation four times. Average time from submission to recommendation was faster for pCODR than NICE (213.8 days vs. 407.9 days; p < 0.001) but the average time to funding decision (see table) was similar (410.1 days in Canada vs. 407.9 days in the United Kingdom; p = 0.71). Conclusions: Although clinically relevant differences in recommendations do exist between NICE and pCODR, neither agency was consistently more restrictive. pCODR recommendations were made more quickly than NICE, but this did not translate into faster funding approval in Canada. Jurisdictional barriers exist for cancer patients which could be mitigated through harmonization and acceleration of drug review processes. [Table: see text]
Racial disparities in treatment and outcomes of colorectal cancer in young adults.
Authors: Alese Olatunji Boladale , Jiang Renjian , Shaib Walid Labib , Wu Christina Sing-Ying , Behera Madhusmita , El-Rayes Bassel F.
Published: September 2018

6559

Background: The incidence of colorectal cancer (CRC) in young adults is increasing. Minority populations with CRC are known to have worse outcome. The objective of this study is to evaluate the impact of race on the outcome of young adults with CRC. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2013. Univariate and multivariate testing was done to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used for association between patient characteristics and survival. Results: A total of 83,449 patients between 18 and 50 years of age were identified. The mean age was 43.6 years (SD±6), with a male preponderance (53.9%). About 72% were non-Hispanic Whites (NHW) while African Americans (AA) made up 15.1%. Distribution across stages I-IV was 15.6%, 22.4%, 33.9% and 27% consecutively, similar among the races. 41.8% of NHW and 28.4% of AA had rectal cancers (p<0.001). Despite equally receiving standard of care (SOC) as per NCCN guidelines, AA had significantly lower 5year survival rates (58.8%) compared to Hispanics (64.8%) and NHW (66.9%; HR 1.42; 1.38-1.46; p<0.001). Patients with colon cancer had worse outcome compared to rectal cancer (HR 1.21; 1.18-1.24; P<0.001). In terms of survival, NHW (HR 0.85; 0.81-0.88; p<0.001) and Hispanics (HR 0.75; 0.70-0.79; p<0.001) were more likely to benefit from chemotherapy compared to AA. As expected, SOC utilization was associated with improved survival across all racial groups, especially in AA with HR of 0.64 (0.60 – 0.69; p<0.001). Conclusions: Despite comparable rates of standard of care utilization, AA young adults with CRC had worse outcomes compared to other races. Colon cancer was significantly more common in AA than rectal cancers, which may have contributed to their worse outcomes. [Table: see text]
Disparities in next generation sequencing in a population-based community cohort of patients with advanced non-small cell lung cancer.
Authors: Presley Carolyn Jean , Soulos Pamela R. , Chiang Anne C. , Longtine Janina A , Adelson Kerin B. , Herbst Roy S. , Nussbaum Nathan C , Sorg Rachael , Abernethy Amy Pickar , Agarwala Vineeta , Gross Cary Philip
Published: September 2018

6563

Background: The use of next generation sequencing (NGS) in patients with advanced non-small cell lung cancer (NSCLC) is increasing. This study explored disparities in the use of NGS testing. Methods: This retrospective observational study utilized Flatiron Health’s longitudinal, demographically and geographically diverse database containing electronic health record data from 191 oncology practices across the U.S. We identified patients diagnosed with advanced (stages IIIB/IV or recurrent) non-squamous NSCLC who received first line treatment and either NGS testing or standard biomarker testing (e.g., EGFR, ALK) alone. NGS included any multi-gene panel testing > 30 genes. Logistic regression modeled the association between patient characteristics and receipt of NGS testing, accounting for clustering of patients by oncology practice. Results: Among 5,688 adults with advanced NSCLC, 4,813 (84.6%) patients received standard biomarker testing alone and 875 (15.4%) patients received NGS testing. The median age of the sample was 67y (IQR: 41-85), the majority was white (63.6%) vs. black (7.5%) vs. unknown (13.4%), and had a history of smoking (79.9%). Among the youngest patients ( < 45y), 31.5% received NGS compared to 11.3% among the oldest (76-85y; P < .001). Approximately 16% of white patients received testing, compared to 11.4% of black patients (P < .001). Patients with Medicaid received testing less often than commercially insured patients (11.7% vs 17.0%; P = .10). Patients had significantly lower odds of receiving NGS testing if they were older (≥75 vs. < 45 years of age; adjusted OR: 0.21, 95% CI: 0.13-0.34), black vs. white race (aOR: 0.63, 95% CI: 0.44-0.90) or were Medicaid vs. commercially insured (aOR: 0.54, 95% CI: 0.30-0.97). Conclusions: Significant age, race, and insurance-related disparities exist in the receipt of NGS testing among patients with advanced lung cancer in real world clinical practice.
What are patients’ biggest concerns? A patient reported outcome case-management system.
Authors: Warsame Rahma M. , Thompson Carrie A. , Hubbard Joleen Marie , Fonder Amie L. , Hobbs Miriam A. , Hwa Lisa , Kourelis Taxiarchis , Gonsalves Wilson I. , Croghan Katrina , Fruth Briant , Dispenzieri Angela , Sloan Jeff A.
Published: September 2018

6572

Background: Cancer patients (pts) receive complex care that may cause physical, emotional, & financial sequelae. Current practice limits clinician time to address patient concerns. The Patient Reported Outcome Quality Of Life (PROQOL) system was developed as a self-reported electronic questionnaire to assess symptoms, QOL and provide data about bothersome issues. Our aim was to determine if the PROQOL system improves QOL without negatively impacting routine clinic workflow. Methods: Eligible pts had multiple myeloma, amyloidosis, head & neck or gynecologic cancer seen in Hematology/Oncology clinics at Mayo Clinic, and were stratified by stem cell transplant and active treatment status. Pts were randomized 2:1 to PROQOL system or usual care. PROQOL system was offered prior to every visit. Pts select from various categories about their single biggest concern, and receive a printed list of actionable resources based on selected concern. Clinicians also receive the PROQOL results to review with pts. Providers and pts randomized to PROQOL completed a “was it worth it survey” (WIWI). An 8 item Linear Analogue Self-Assessment was used to assess QOL. The study was powered to detect a 0.5 standard deviation difference in QOL between groups. Herein we report the planned results of first 6 months. Results: Among the first 118 pts accrued, 55% were female, median age was 63 (32-86), & 93% were on therapy. Median time from diagnosis to PROQOL was 26 months. The PROQOL system took 3.6 minutes to complete. Baseline median QOL (range) was 7 (3-10) for both groups. The most common PROQOL issue selected was “cancer & diagnosis” (36.5%) followed by “physical health” (35.3%). Specific concerns were related to treatment plan, prognosis, fatigue, sleep, and neuropathy. WIWI showed: 71% of pts thought it was worthwhile, 83% would participate again, 80% would recommend it, & 65% used resources provided. 80% of providers reported the PROQOL did not interfere with care & 75% believed the pt wellbeing may improve. Conclusions: Notably treatment plan & prognosis remain pts' greatest concern despite being over 2 year from diagnosis.The PROQOL system demonstrates integrated PRO reporting in clinic is quick & worthwhile to pts & providers.
Self-reported health and access to care among cancer caregivers: Analysis of the 2015 behavioral risk factor surveillance system (BRFSS).
Authors: Castellanos Emily , Nikpay Sayeh
Published: September 2018

6573

Background: Caregivers play a vital role in the support and treatment of cancer patients. Caregiver well-being can impact patient-perceived quality of care. The study objectives were to compare self-reported health and access to care between cancer caregivers and non-caregivers, and to determine the relationship of caregiving burden to self-reported health and access to care. Methods: We used data from the Caregiver and Core Modules of the 2015 BRFSS, an annual federal survey of health-related behavior, health conditions, and preventive service use. Caregiver burden was assessed by time (hours per week and duration of caregiving) and task (personal care and household management tasks). Measures of self-reported health and access to care between cancer caregivers and non-caregivers were compared using t-test or Chi-Square testing. Associations of caregiver burden with self-reported health and access to care were assessed with linear and logistic regressions. Results: 1,910 cancer caregivers and 84,412 non-caregivers were included. Compared to non-caregivers, cancer caregivers were more likely to report inability to see a physician due to cost (15% vs 9%; p < 0.001), depression (25.0% vs 17.9%; p < 0.001), and poor mental health (mean days per month 5.7 vs 3.1; p < 0.001). Compared to caregivers with low task burden, those with moderate or high task burden reported both more poor mental health days (moderate ß = 1.8, 95% CI 0.5 – 3.1, p = 0.008; high ß = 2.0, 95% CI 0.6 – 3.3, p = 0.004) and increased likelihood of cost barriers (moderate OR 1.6, 95% CI 1.03 – 2.5, p = .035; high OR 1.8, 95% CI 1.2 – 2.9, p = .008). Increased time burden was associated with more poor mental health days (moderate ß = 1.5, 95% CI 0.2 – 2.7, p = .02; high ß = 4.4, 95% CI 3.3 – 5.6, p < .001) but not cost barriers. No differences in insurance, personal health provider, medical check-ups, or self-reported poor physical health were identified. Conclusions: Cancer caregivers are more likely than non-caregivers to report poor mental health, depression, and difficulty seeing a physician due to cost. Caregivers with high caregiving burden are at increased risk of experiencing poor mental health and cost barriers to medical care.
Association between progression-free survival and health-related quality of life in oncology: A systematic review and regression analysis.
Authors: Kovic Bruno , Jin Xuejing , Thabane Lehana , Guyatt Gordon , Brundage Michael Donald , Xie Feng ,   PFS-HRQoL Review Team
Published: September 2018

6574

Background: The goal of cancer care is to improve not only survival duration but also health-related quality of life (HRQoL). Progression-free survival (PFS) has become an important surrogate outcome in assessing efficacy of new cancer drugs, but the relationship between improved PFS and HRQoL is not clear, particularly in the absence of an overall survival (OS) benefit. The objective of this study was to examine the relationship between PFS and HRQoL through a systematic review and analysis of published evidence. Methods: We searched MEDLINE, Embase, and Cochrane databases for randomized controlled human trials addressing oncology treatments published since 2000. We utilized the difference in median PFS time duration between treatment groups, with eligible trials being those reporting no significant OS benefit. We calculated and compared HRQoL between treatment groups using the difference in standardized mean incremental area under the curve adjusted to per month values. Weighted simple regressions were used to examine the PFS-HRQoL association, separately for physical, emotional, and global HRQoL domains. Results: 35,960 citations were identified, with 42 final articles reporting 30 clinical trials being eligible for inclusion. The 30 trials involved 10,731 patients across 12 types of cancer using 6 different instruments. 67% of all trials had improved PFS, and 56%, 54%, and 62% of trials had improved physical, global, and emotional HRQoL, respectively. The PFS with physical domain (n = 18) regression coefficient (slope) β = -0.205 (95% CI; -0.649 to 0.239), with emotional domain (n = 13) β = 0.775 (95% CI; -0.048 to 1.598), and with global domain (n = 24) β = 0.094 (95% CI; -0.271 to 0.459). Conclusions: Our systematic review and analyses revealed weak and nonsignificant association between PFS and HRQoL. In the absence of OS benefit, when longer PFS doesn’t correspond to better HRQoL, using PFS as the proxy for efficacy for oncology drugs is problematic.
Correlation of changes in disposition of geriatric (≥ 65 years) cancer patients receiving hematopoietic stem cell transplantation with an increase in healthcare costs.
Authors: Guddati Achuta Kumar , Joy Parijat Saurav , Kumar Gagan , Shapira Iuliana
Published: September 2018

6578

Background: The increasing proportion of geriatric cancer patients in the general population has contributed to rising health care costs. The disposition of hematopoietic stem cell transplant (HSCT) recipients in the geriatric population is an important factor determining the cost of their health care. A database with nationwide representation for outcomes of HSCT over a 12 year period was analyzed. Methods: Data regarding patients who underwent HSCT was extracted from the Nationwide Inpatient Sample (NIS) from 2000 to 2011 using ICD-9-CM codes. HSCT hospitalizations were classified into allogeneic transplantation, autologous transplantation, subsequent hospitalization (s/p transplant) with graft versus host disease (GVHD) and subsequent hospitalization (s/p transplant) with other complications. NIS variables were used to identify in-hospital complications and discharge disposition. Results: The proportion of elderly patients (≥ 65 years) who received any type of transplant or were admitted with GVHD or other related complications who were discharged with additional support and to specialized facilities has increased over the past decade. The exception to this trend has been noted for allogeneic transplants and may be due to a more conservative approach towards their disposition (ie, higher level of care and longer length of stay). The trends from 2000 to 2011 are summarized in the table below. Conclusions: A higher percentage of geriatric cancer patients who receive HSCT are being discharged to nursing homes. These rates have significantly changed over the past decade (p > 0.05) and represents an additional contribution to the rising health care costs. This proportion of patients are expected to rise as increasingly older patients are being allowed to receive HSCT and represents a higher future demand for health care services. [Table: see text]
Symptom burden and hospital length of stay among patients with curable cancer.
Authors: D'Arpino Sara , El-Jawahri Areej , Moran Samantha M.C. , Johnson Connor , Lage Daniel , Wong Risa , Xiao Yian , Ruddy Margaret , Temel Brandon , Pirl William F. , Traeger Lara , Lennes Inga Tolin , Cashavelly Barbara J. , Martinson Holly S , Jackson Vicki A. , Greer Joseph A. , Ryan David P. , Hochberg Ephraim P. , Temel Jennifer S. , Nipp Ryan David
Published: September 2018

6579

Background: Prolonged hospital admissions are often inconsistent with patients’ preferences and incur significant costs. While patients’ symptoms may result in hospitalizations, the relationship between patients’ symptom burden and their hospital length-of-stay (LOS) has not been fully explored in patients with curable cancers. Methods: We prospectively enrolled patients with curable cancer and unplanned hospital admissions between 8/2015 and 12/2016. Within the first 5 days of admission, we assessed patients’ physical (Edmonton Symptom Assessment System [ESAS]; scored 0-10 with higher scores indicating greater symptom burden) and psychological symptoms (Patient Health Questionnaire 4 [PHQ-4]; scored categorically and continuous with higher scores indicating greater distress). We created summated ESAS total and physical symptom variables. To assess the relationship between patients’ symptom burden and their hospital LOS, we used separate linear regression models adjusted for age, sex, marital status, education level, time since cancer diagnosis, and cancer type. Results: We enrolled 452 of 497 (91%) approached patients (mean age = 61.9 years; 188 [42%] female). Over half had hematologic cancers (n = 249, 55%). Mean hospital LOS was 8.3 days. Over one-tenth of patients screened positive for PHQ-4 depression (n = 74, 16%) and anxiety (n = 60, 13%) symptoms. Mean ESAS symptom scores were highest for fatigue (6.6), drowsiness (5.4), pain (4.9), and lack of appetite (4.8). In multivariable regression analysis, patients’ physical and psychological symptoms were associated with longer hospital LOS (table). Conclusions: Patients with curable cancer and unplanned hospital admissions experience a substantial symptom burden, which predicts for prolonged hospitalizations. Importantly, patients’ symptoms are modifiable risk factors that, if properly addressed, can improve care delivery and may have the potential to help decrease prolonged hospitalizations. [Table: see text]
Examining the relationship between cost of novel oncology drugs and their clinical benefit over time.
Authors: Saluja Ronak , McDonald Erica , Arciero Vanessa Sarah , Cheng Sierra , Cheung Matthew C. , Chan Kelvin K.
Published: September 2018

6598

Background: The average launch price of oncology drugs has increased by 10% annually from 1995 to 2013. The purpose of this study was to determine if the clinical benefit of novel oncology drugs has increased proportionally over time and is correlated with launch price. Methods: Novel oncology drugs fromrandomized controlled trials (RCTs) cited for clinical efficacy evidence in drug approvals between January 2006 and August 2015 were identified. For each drug, only the first FDA approved indication was included. To determine clinical benefit, all included RCTs were scored using the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale. The launch price for the FDA approval year of each drug was extracted from RedBook. Each drug’s 28-day cost was determined using the dosage schedule outlined in the respective RCT and was adjusted to 2015 USD using the consumer price index. The relationships between 28-day drug cost and FDA approval year, and between incremental drug cost (difference in total drug cost between experimental and control arms accounting for treatment duration) and FDA approval year were examined using generalized linear regression models (gamma distribution and log link). Ordinary least square models were used to evaluate the relationship between ASCO/ESMO scores and FDA approval year. Spearman’s correlation coefficients between 28-day/incremental drug costs and ASCO/ESMO scores were also calculated. Results: Forty RCTs were included in this analysis. The 28-day drug cost was significantly associated with FDA approval year (p = 0.04), with an average increase of 8.5% per year. Incremental drug cost was also significantly associated with FDA approval year (p < 0.001) with an increase of 28.6% per year. The mean ASCO and ESMO scores were 26 and 3, respectively. Both scores were not statistically associated with FDA approval year (p = 0.73 and p = 0.86, respectively) and were also not correlated with 28-day or incremental drug costs (all rho < = 0.2). Conclusions: Novel oncology drugs are not priced according to their clinical benefit. The rising cost of novel oncology drugs over time is not associated with an increase in their clinical benefit, suggesting a decrease in their value over time.
Total and out-of-pocket costs of different primary management strategies in ovarian cancer.
Authors: Suidan Rudy Sam , He Weiguo , Sun Charlotte C. , Zhao Hui , Lu Karen H. , Giordano Sharon Hermes , Meyer Larissa
Published: September 2018

6602

Background: Communicating healthcare costs to pts is an important component of delivering high-quality value-based care, yet cost data are lacking. This is especially relevant for epithelial ovarian cancer (OC), where no clinical consensus on optimal first-line treatment exists. Our objective was to generate cost estimates of different primary management strategies in OC. Methods: All women who underwent primary treatment for OC from 2006 – 2015 were identified from MarketScan, a claims database of commercially insured US pts (n = 12,761). Pts were classified based on: 1) whether they underwent primary debulking surgery followed by postoperative chemotherapy, or neoadjuvant chemotherapy followed by interval debulking; 2) type of chemotherapy regimen administered (intravenous [IV] every 3 weeks [Standard], IV every week [Dose-dense], or intraperitoneal [IP]/IV); and 3) if regimens included bevacizumab (Bev). Total and out-of-pocket (OOP) costs were calculated using all claims within 8 months from initial treatment and were normalized to 2015 US dollars. A generalized linear model was used to assess cost by strategy adjusting for clinical and demographic factors. Results: Mean adjusted total and OOP costs for the different treatment strategies/regimens are shown in the table. Among pts who did not receive Bev, 25% paid ≥$3964 and 10% paid ≥$5875. For pts who received Bev, 25% paid ≥$4201 and 10% paid ≥$6222. Among pts enrolled in high-deductible health plans, mean OOP costs were $4680, with 25% of pts paying ≥$6264 and 10% paying at least $9144. Conclusions: Costs vary across different treatment strategies and pts bear a significant OOP burden, especially those enrolled in high-deductible plans. As no consensus exists on optimal first-line management for OC, these data may help inform value-based discussions between providers and pts. [Table: see text]
Differences in medical care costs for recurrent versus de novo stage IV cancer by age at diagnosis.
Authors: Banegas Matthew P. , Hassett Michael J. , Fishman Paul A , Hornbrook Mark C. , Carroll Nikki M , Cronin Angel M. , O'Keeffe-Rosetti Maureen Cecelia , Uno Hajime , Ritzwoller Debra P.
Published: September 2018

6611

Background: To address the paucity of data on costs of cancer recurrence, this study estimated medical care costs of patients diagnosed with recurrent breast, colorectal or lung cancer, and compared costs to patients diagnosed with de novo stage IV disease. Methods: Data from patients enrolled in three health plans who were diagnosed with de novo stage IV or recurrent breast (nstage IV = 352; nrecurrent= 765), colorectal (nstage IV = 1072 and nrecurrent= 542) and lung (nstage IV = 4042 and nrecurrent= 339) cancers between 2000-2012 were used to estimate total medical care costs in the 12 months preceding (pre-index), month of index, and 12 months following (post-index) diagnosis/recurrence date. Cancer patients were identified using tumor registry data. Recurrent cancers were validated by medical record abstraction and the RECUR algorithms –innovative tools to detect recurrence using claims and electronic health record data. We used generalized linear repeated measures regression models controlling for demographic and comorbidity variables to estimate costs (2012 US$), stratified by age at diagnosis (ages < 65, ≥65). Results: Medical care cost differences in the pre-index period indicate higher costs for recurrent cancer patients than for stage IV breast (Age < 65:+$2550; Age ≥65: +$1254), colorectal (Age < 65:+$3295; Age ≥65: +$1653), and lung cancer patients (Age < 65:+$3232; Age ≥65: +$2340). Conversely, in the index and post-index periods, costs for stage IV cancers were higher than recurrent cancer costs. Specifically, post-index period cost differences indicate higher costs for stage IV patients than for recurrent breast (Age < 65:+$683; Age ≥65: +$1172), colorectal (Age < 65:+$3104; Age ≥65: +$1557), and lung cancer patients (Age < 65:+$1136; Age ≥65: +$1103). Conclusions: Our study provides medical care cost estimates of recurrent and de novo stage IV cancers. Cost differences between recurrent and stage IV cancers reveal heterogeneity in care patterns that merits further investigation. The reported study costs, measured in capitated care systems using standardized fee-for-service reimbursement coefficients, may serve as a benchmark for stage-specific phase-of-care oncology episode payment models.
Validation of a financial toxicity (FT) grading system.
Authors: De Souza Jonas A. , Wroblewski Kristen , Proussaloglou Ellie , Nicholson Laura , Hantel Andrew , Wang Yichen
Published: September 2018

6615

Background: FT is an important adverse event (AE) that should be objectively measured in clinical practice. We previously developed an evidence-based FT grading system based on differences in HRQoL, analogous to the NCI-Common Terminology Criteria for Adverse Events (grade 1, mild AE; grade 2, moderate AE; grade 3, severe AE ,de Souza et al - ASCO 2015). We aimed to validate this grading system using a new sample of cancer patients (pts) and report its association with bankruptcy. Methods: FT was assessed by the COST (COmprehensive Score for financial Toxicity) in 2 sets of cancer pts. In the previously reported Development Set (DS), gradations of FT were determined by ROC analyses based on conventions for clinically meaningful small (0.2), medium (0.5) and large (0.8) effect sizes (e.s.) for independent FACT-G differences attributable to FT in pts with Stage IV cancers on chemotherapy. In the Validation Set (VS), differences in HRQoL and the odds ratio for a pt to have declared bankruptcy after the cancer diagnosis were assessed in a larger cohort of cancer pts on chemotherapy. Results: The grading system was developed in 888 cancer pts with cancer (233 pts in the DS and 655 in the VS). In the DS, ROC analyses produced 4 FT grades (G): G0, no FT, COST ≥26 (99 pts, 42%); G1, mild FT: ≥ 14-26 (71 pts, 31%); G2, moderate FT: > 0-14 (58 pts, 25%); and G3, severe FT: COST = 0 (5 pts, 2%). Applying the FT grading to the 655 pts in VS, we had: G0, 146 pts (22%); G1, 281 (43%); G2, 215 (33%); and G3, 13 (2%). The decreases in FACT-G HRQoL measured in e.s. per FT grading in comparison with G0 were small for G1: -0.4 (95%CI: -0.6 – -0.25); large for G2: -0.9 (95%CI: -1.1 – -0.7); and even larger for G3: -1.5 (95%CI: -2.0 – -0.9), all with p < 0.001. In the VS, 23 pts (4%) had declared bankruptcy after their cancer diagnosis. Compared to FT G0, the odds of having declared bankruptcy were 8.6 (95%CI: 1.1 – 67, p = 0.04) times higher for pts with FT G2, and 29 times higher (95% CI: 2.4 – 355, p = 0.008) for those with G3 FT. Conclusions: We developed a FT grading system anchored on independent differences in HRQoL. We applied the system in a different set of cancer pts and it retained its validity. We also found an larger incidence of bankruptcy after the cancer diagnosis in higher grades of FT, adding to the grading’s meaningful use.
Bosutinib (BOS) versus imatinib (IM) for newly diagnosed chronic myeloid leukemia (CML): Initial results from the BFORE trial.
Authors: Cortes Jorge E. , Gambacorti-Passerini Carlo , Deininger Michael W.N. , Mauro Michael J. , Chuah Charles , Kim Dong-Wook , Reilly Laurence , Jeynes-Ellis Allison Marianne , Leip Eric , Bardy-Bouxin Nathalie , Hochhaus Andreas , Brümmendorf Tim H. ,   On Behalf of the BFORE Study Investigators
Published: September 2018

7002

Background: BOS is a potent, dual SRC/ABL tyrosine kinase inhibitor approved for treatment (tx) of adults with Ph+ CML resistant/intolerant to prior therapy. We assessed the efficacy and safety of BOS vs IM for first-line tx of chronic phase (CP) CML. Methods: In this ongoing, multinational, phase 3, open-label study, 536 patients (pts) with newly diagnosed CP CML were randomized 1:1 to BOS 400 mg QD (n = 268) or IM 400 mg QD (n = 268 [3 not treated]). Per protocol, efficacy was assessed in a modified intent-to-treat (ITT) population of 487 Ph+ pts (BOS, n = 246; IM, n = 241) with e13a2/e14a2 transcripts; results in full ITT will also be presented. Results: After≥12 mo of follow-up, 78% of BOS and 73.2% of IM pts remain on tx with median tx durations of 14.1 and 13.8 mo, respectively. Major molecular response (MMR) rate at 12 mo (primary endpoint) was significantly higher with BOS vs IM (47.2% vs 36.9%; P= 0.02). Time to MMR was shorter for BOS (hazard ratio [HR] 1.34; P< 0.02). Rate of complete cytogenetic response (CCyR) by 12 mo was also significantly higher with BOS vs IM (77.2% vs 66.4%; P< 0.008), with time to CCyR shorter for BOS (HR 1.38; P≤0.001). Rates of BCR-ABL transcripts≤10% (Intl Scale) at 3 mo (75.2% vs 57.3%), MR4 at 12 mo (20.7% vs 12%) and MR4.5 at 12 mo (8.1% vs 3.3%) were higher with BOS vs IM, respectively (all P< 0.025). 1 BOS pt and 4 IM pts discontinued tx due to progression to accelerated or blast phase. There were no deaths within 28 d of last dose of BOS and 4 with IM. Safety data were consistent with known safety profiles of BOS and IM. 12.7% of BOS and 8.7% of IM pts discontinued due to drug-related toxicity. Gr≥3 diarrhea (7.8% vs 0.8%) and increased alanine (19% vs 1.5%) and aspartate (9.7% vs 1.9%) aminotransferase levels were more common with BOS. Cardio-, peripheral- and cerebrovascular events were infrequent (3%, 1.5% and 0% BOS vs 0.4%, 1.1% and 0.4% IM; gr≥3: 1.5%, 0% and 0% vs 0%, 0% and 0.4%). Conclusions: Pts on BOS had significantly higher rates of 12-mo MMR and CCyR and achieved responses faster than those on IM, but had higher incidence of gastrointestinal events and transaminase elevations. Results suggest BOS may be an important tx option for pts with newly diagnosed CP CML. Funding. Avillion, Pfizer. Clinical trial information: NCT02130557 .
Deep molecular response to gilteritinib to improve survival in FLT3 mutation-positive relapsed/refractory acute myeloid leukemia.
Authors: Altman Jessica K. , Perl Alexander E. , Cortes Jorge E. , Smith Catherine Choy , Litzow Mark Robert , Hill Jason E , Larson Richard A. , Liu Charles , Ritchie Ellen K. , Strickland Stephen Anthony , Wang Eunice S. , Neubauer Andreas , Martinelli Giovanni , Bahceci Erkut , Levis Mark J.
Published: September 2018

7003

Background: Gilteritinib, a highly selective FLT3/AXL inhibitor, has displayed antileukemic activity in FLT3 mutation-positive (FLT3mut+) relapsed/refractory (R/R) AML in the CHRYSALIS Phase I/II study (NCT02014558), specifically at doses ≥80 mg/d. This exploratory analysis assessed molecular response to gilteritinib in a CHRYSALIS subpopulation. Methods: Molecular response was assessed from bone marrow aspirates obtained at baseline and at ≥1 additional time point from FLT3mut+ patients (≥18 y) treated with 120 or 200 mg/d gilteritinib. These doses were identified due to their ability to induce consistent, potent FLT3 inhibition and high clinical response rates. FLT3-ITD and total FLT3 were quantified by NGS to assess molecular response. A Cox regression model of overall survival (OS) by Kaplan-Meier estimation established a FLT3-ITD:total FLT3 ratio (ITD signal ratio) of 10−2as the threshold for improved survival. Results: Of 147 FLT3-ITDmut+ patients who received gilteritinib 120 or 200 mg/d, 80 were included in this analysis. Composite response rate for these 80 patients was 55%. During response, 20 patients (25%) had an ITD signal ratio of ≤10−2. Of these 20 patients, 18 had a ratio of ≤10−3 (major molecular response [MMR]) and 13 had a ratio of ≤10−4 (minimal residual disease [MRD] negative). Median time to achieve minimum signal ratio was 54 days. Elimination of morphologic leukemia was observed in 80% of patients with ITD signal ratios <10−2. Patients who had a signal ratio ≤10−2, MMR, or were MRD negative had significantly longer median OS than those who did not (Table). Conclusions: Molecular responses to gilteritinib in FLT3-ITDmut+ R/R AML correlated with clinical response and improved OS. This is the first demonstration of molecular response to a FLT3 inhibitor in AML. These data suggest ITD signal ratio may predict durable clinical benefit of gilteritinib. Clinical trial information: NCT02014558. [Table: see text]
Phase IB/II study of nivolumab with azacytidine (AZA) in patients (pts) with relapsed AML.
Authors: Daver Naval Guastad , Basu Sreyashi , Garcia-Manero Guillermo , Cortes Jorge E. , Ravandi Farhad , Jabbour Elias , Hendrickson Stephany , Brandt Mark , Pierce Sherry , Gordon Tauna , Pemmaraju Naveen , Andreeff Michael , Ning Jing , Kornblau Steven , Kadia Tapan M. , Dinardo Courtney Denton , Konopleva Marina , Allison James Patrick , Kantarjian Hagop M. , Sharma Padmanee
Published: September 2018

7026

Background: Blocking PD-1/PD-L1 pathways enhances anti-leukemia responses in murine AML (Zhang et al, Blood 2009). PD-1 positive CD8 T-cells are increased in bone marrow (BM) of pts with AML (Daver et al, ASH 2016). AZA up-regulates PD-1 in AML (Yang et al., Leukemia 2013). Methods: Pts were eligible if they had AML and failed prior therapy, had adequate performance status (ECOG ≤ 2), and organ function. AZA 75mg/m2Days 1-7 with nivolumab 3mg/kg on Day 1 and 14 was established as the recommended phase II dose. Courses were repeated every 4-5 weeks indefinitely. Responses were evaluated at the end of 3 courses. Results: 53 pts with med age 68 years (range, 44 – 90), secondary AML (43%), poor risk cytogenetics (43%), med prior regimens 2 (range, 1-7) have been enrolled. Common mutations included DNMT3A (n = 11), TP53 (n = 11), TET2 (N = 8), CEBPA (n = 8), ASXL1(n = 8). All 53 pts are evaluable for response: 11 (21%) achieved CR/CRi and 7 (14%) had hematologic improvement (HI) for an overall response rate of 35%. Additionally, 14 (26%) had ≥50% BM blast reduction, 3 (6%) had stable disease > 6 months, and 12 (23%) had progression. The CR/CRi have been durable with 9 of 11 (82%) pts with CR/CRi alive at 1 year, after censoring for SCT. Med survival for the 53 evaluable pts was 5.7 months (range, 0.9 – 16.2) and in the 27 salvage 1 pts was 9.3 months (range, 1.6 – 16.2). These compare favorably to historical survival with AZA-based salvage protocols at MDACC. Grade 3/4 and Grade 2 immune toxicities were observed in 7 (14%) and 6 (12%) pts, respectively. These responded rapidly to steroids and 12 of 13 pts were successfully rechallenged with nivolumab. Multicolor flow-cytometry data were available on pretherapy, end of cycle 1, and end of cycle 2 BM aspirates in 9 CR/CRi and 22 non-responders. Pts who achieved CR/CRi had higher pre-therapy total CD3 (P = 0.02) and higher CD8+ T-cells (P = 0.07) infiltrate in the BM. Responders demonstrated progressive increase in BM CD8+ and CD4+ infiltrate. Both responders and non-responders had increase in CTLA4+ CD8+ cells on therapy. Conclusions: Full dose AZA and nivolumab are tolerable and may produce durable responses in relapsed AML. Up-regulation of CTLA4 may be a mechanism of resistance to PD1 based therapies in AML. Clinical trial information: NCT02397720.
Updated results of frontline ofatumumab-hyper-CVAD in adults with CD20+ acute lymphoblastic leukemia.
Authors: Maiti Abhishek , Kantarjian Hagop M. , Ravandi Farhad , Thomas Deborah A. , Khouri Maria , Garcia-Manero Guillermo , Garris Rebecca S. , Cortes Jorge E. , Short Nicholas James , Sasaki Koji , Issa Ghayas C. , Koller Paul B. , Schroeder Heather M , Kadia Tapan M. , Verstovsek Srdan , Daver Naval Guastad , Jain Nitin , Konopleva Marina , O'Brien Susan Mary , Jabbour Elias
Published: September 2018

7033

Background: Chemoimmunotherapy is an effective frontline therapy for acute lymphoblastic leukemia (ALL). Ofatumumab (O) binds to a proximal small-loop epitope on CD20 and is more potent in vitro than rituximab. Here we report interim results of its combination with hyper-CVAD (HCVAD) in adult patients (pts) with CD20+ ALL. Methods: Since 7/2011, we have enrolled 63 pts with Ph-negative CD20+ ALL (59 newly diagnosed, 4 previously treated). For the intensive phase, pts received 4 cycles (cy) of HCVAD (odd cy 1, 3, 5, 7) alternating with 4 cy of methotrexate-cytarabine (MTX-Ara-C, even cy 2, 4, 6, 8), and ofatumumab during cy 1-4. For maintenance, pts received POMP for ~30 months (mos), and intensification with MTX/PEGylated asparaginase on mos 6 and 18, and O-HCVAD on mos 7 and 19. Intrathecal MTX-Ara-C was used for CNS prophylaxis. Bulky mediastinal disease was irradiated when indicated. Results: Median age was 41 years (range: 18-71) and median WBC count was 4.6 x109/L (range: 0.6-201 x109/L). 22 pts (35%) had diploid cytogenetics and 8/35 pts (23%) had TP53 mutation. CD20 expression was > 20% in 38 pts (60%), 10-20% in 6 pts (10%) and 1-10% in 16 pts (25%). Median follow-up was 20 mos (range: 1-58) and median number of cy was 8 (range: 1-8). 3 pts (5%) were in CR at the time of enrollment. Of 60 pts evaluable for response, 58 pts (97%) achieved CR; 1 pt achieved CRp and 1 pt died during cy 1 from sepsis. Flow cytometric minimal residual disease (MRD) was negative in 57/62 pts (92%) overall, and in 36/57 pts (57%) at CR. Median time to negative MRD was 0.7 mos. Median time to platelet and neutrophil recovery in cy 1 was 21 and 18 days, respectively. The most common grade 3/4 non-hematological toxicities were infections during induction (49%) and consolidation (72%), elevated transaminases (35%), and hyperbilirubinemia (21%). 5 pts (7%) experienced a grade 3/4 transfusion reaction. 8 pts (13%) received stem cell transplantation in CR1. 10 pts (16%) have relapsed (8 morphological, 2 MRD only). Overall survival and 2-year CR duration rates were 80% and 81%, respectively. Survival outcomes were independent of percentage of CD20 expression. Conclusions: O-HCVAD is safe, effective and results in durable responses in pts with CD20+ ALL. Clinical trial information: NCT01363128.
Ten-year survival after randomized comparison of imatinib (IM) 400 mg vs. IM 800 mg vs. IM + IFN vs. IM + Ara C vs. IM after IFN in chronic myeloid leukemia (CML).
Authors: Hehlmann Ruediger , Lauseker Michael , Saussele Susanne , Pfirrmann Markus , Neubauer Andreas , Krause Stefan W. , Hossfeld Dieter K. , Nerl Christoph , Baerlocher Gabriela M. , Heim Dominik , Kolb Hans-Jochem , Proetel Ulrike , Kohlbrenner Katharina , Gratwohl Alois , Burchert Andreas , Voskanyan Astghik , Rinaldetti Sebastien Ly , Hochhaus Andreas , Hasford Joerg ,   SAKK and German CML Study Group
Published: September 2018

7049

Background: It is unclear whether IM 400 mg is the optimum choice for the successful treatment of CML. Treatment optimization was therefore attempted. Methods: From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase (CP) were randomized into a 5-arm study to analyze 2 IM doses and 3 combinations. 1536 patients were evaluable, 400 for IM 400 mg, 420 for IM 800 mg, 430 for IM + Interferon (IFN), 158 for IM + Ara C and 128 for IM after IFN. Recruitment to the latter two arms was stopped after a pilot phase. Results: 10-year overall survival (OS) of all patients was 82%, 10-year progression free survival (PFS) 80%. 10-year OS was 80% with IM 400 mg, 79% with IM 800 mg, 84% with IM + IFN, 84% with IM + Ara C and 79% with IM after IFN. The differences were not significant. 10-year PFS was 80% with IM 400mg, 77% with IM 800mg, 83% with IM + IFN, 82% with IM + Ara C and 75% with IM after IFN. The differences were not significant either. Survival with any treatment was not significantly different from IM 400mg at any risk level by any risk score (Euro Sokal, EUTOS, ELTS). 87 patients progressed to blast crisis (BC). The 10-year cumulative incidence of BC was 5.8% (95% CI: 4.7%; 7.1%) equally distributed across treatment arms. Most BC occurred in the first 2 years. Median survival after BC was 7.9 months across treatment arms. 275 patients have died, 23 after stem cell transplantation in first CP. Two thirds of deaths were unrelated to CML. Incidence of death due to CML by competing risk analysis with death unrelated to CML as competing risk was not different between the 5-treatment arms. 10-year relative survival probability was 92% when compared to matched general population data. Patients reaching the cytogenetic or molecular response landmarks according to European LeukemiaNet criteria ( < 10% BCR-ABL IS at 3 months, < 1% BCR-ABL IS or complete cytogenetic remission at 6 months, < 0.1% BCR-ABL IS (MMR) at 12 months) had a significantly better survival than those not reaching the landmarks regardless of therapy. Conclusions: In conclusion, outcome of CML is currently more determined by prognostic markers than by choice of therapy. IM400 mg remains an excellent choice for initial therapy of CP-CML. Clinical trial information: NCT00055874.