bluuebunny/crossref_metadata_2025_split huggingface dataset:
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]