bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short and long term impact of financial toxicity on quality of life in the Carolina Breast Cancer study.
Authors: Spencer Jennifer , Reeder-Hayes Katherine Elizabeth , Pinheiro Laura C , Carey Lisa A. , Olshan Andrew F , Wheeler Stephanie B. 
Published: September 2018

e18299 Background: High cancer treatment costs are associated with considerable distress and worse outcomes in cancer patients, a phenomenon known as “financial toxicity”. We examined changes in health-related quality of life (HRQoL) among women experiencing financial toxicity after cancer diagnosis compared to cancer patients without financial toxicity in a racially diverse cohort of breast cancer patients. Methods: HRQoL was self-reported at approximately 5 and 25 months post-diagnosis using the Functional Assessment of Cancer Treatment (FACT-G) in a prospective, population-based, cohort study with oversampling of Black and young (<50 years old) women. Women reported on the financial burden of their breast cancer, including whether they had declined or delayed care due to cost or transportation barriers and whether they lost a job, experienced a reduction in household income, or lost insurance coverage after their cancer diagnosis. We assessed changes in HRQoL from 5 to 25 months according to financial toxicity experience. Results: 2,432 women completed 5- and 25-month HRQoL surveys and were included in analyses. Forty-nine percent were non-Hispanic Black and 51% were non-Hispanic White; other minorities were excluded due to small numbers. Overall, 49% of women reported at least one indicator of financial toxicity (59% Black vs. 39% White). Women who reported any financial toxicity had significantly lower scores on the FACT-G at baseline (75.5 vs 87.2, p<0.001) and reported significantly less improvement in HRQoL from 5- to 25-months than women who did not report financial toxicity (incremental difference: +1.4 vs +3.8, p=.01). Black women reported lower overall HRQoL than White women (p=0.03), but impact of financial toxicity on HRQOL was similar among black and white women in stratified analyses. Conclusions: Financial toxicity is associated with lower HRQoL and with less improvement in HRQoL in the two years following breast cancer diagnosis. [Table: see text]
Acute care reliance among patients with advanced cancer with or without nurse navigation.
Authors: Kowalkowski Marc , Blackley Kris , Farhangfar Carol J. 
Published: September 2018

e18303 Background: Acute care utilization is a key component of health care cost among oncology patients, particularly at advanced stages. Oncology nurse navigation (NN) was developed to improve access to quality cancer care but little is known about the impact of NN on acute care reliance (ACR) among patients with advanced cancer. Methods: A cohort study was conducted among adults (≥18) diagnosed with advanced-stage (III/IV) first primary solid tumor (10 most common solid tumors by annual incidence - bladder, breast, colon, kidney, lung, melanoma, pancreas, prostate, thyroid, uterus) from January 2013-December 2015. For inclusion, NN patients had to initiate NN services ≤30 days after diagnosis and all patients must have had ≥30 days of follow-up. The primary outcome was ACR, defined as the proportion of total health care utilization received in an acute care setting (hospital inpatient/observation, emergency department), from diagnosis through 1 year, calculated per 30-day interval to adjust for follow-up variance. To assess the effect of NN receipt on ACR, generalized linear models were fit specifying a gamma distribution and a log-link function, adjusted for patient and clinical characteristics at diagnosis. Subgroup analyses were conducted in patients surviving < 6 and ≥6 months. Results: 2950 patients with advanced cancer were followed (NN = 970 [33%]). Lung (37%), prostate (13%) and breast (12%) cancers were most common. 944 (32%) patients died during the 1-year interval. Patients averaged 1.7 health care encounters per 30-day interval. Those who received NN had lower mean ACR than patients who did not, overall (0.18 vs 0.30; p < 0.001) and in each individual cancer type (p < 0.05) except melanoma (p = 0.4). In multivariable models, NN receipt was associated with decreased ACR (RR = 0.65 95%CI = 0.60-0.70). The effect of NN on ACR was consistent in subgroups defined by survival duration. Conclusions: Patients with advanced cancer who received NN were less reliant on acute care than patients who did not receive NN. Given the role of acute care in driving health care cost and the inverse association between increased ACR and health care quality, our findings may have important implications for improving value in oncology care.
Evaluation of value in non-inferiority trials by ASCO’s conceptual framework.
Authors: Miyamoto Kenichi , Nakamura Kenichi , Fukuda Haruhiko 
Published: September 2018

e18304 Background: ASCO released a conceptual framework assessing the value of cancer treatment options in 2015 and its updated version in 2016 as a tool to evaluate clinical benefit and toxicity in clinical trials. This framework was developed as a facilitator of discussions on the individual treatment between physicians and their patients. This tool consists of the elements of clinical benefit, toxicity, and symptom palliation, and these elements are combined into a score termed the net health benefit (NHB). However, in the clinical setting, not only these elements but also various factors benefit patients such as more convenient treatment schedule, shorter administration time, or non-invasive route of administration. Especially, test treatment in non-inferiority trials is likely to have these merits in addition to the benefit in toxicity. Therefore, we investigated whether the ASCO framework can identify reasonable NHB in test treatment regimens of non-inferiority trials. Methods: A systematic literature search of randomized non-inferiority trials for cancer reported from 2009 to 2015 was performed using PubMed. Inclusion criteria were English, a full-length article, available toxicity data, non-inferiority trial with a positive result, and chemotherapy. We calculated clinical benefit, toxicity score, bonus points, and NHB according to the ASCO framework. Results: We found 20 non-inferiority trials. Median sample size was 419. The common cancer types were colorectal (7 trials), lung (5), hematologic (2), and breast (2). Of 20 trials, 8 were conducted internationally, 4 in Japan, and 3 in Germany. In the ASCO framework, median NHB was 4.5 points, and 7 of 20 trials (35%) showed negative impact of test treatment, which means that NHB was minus points (-0.6 to -24.53). In 6 of these 7 trials, test treatment was in more convenient schedule or administered by non-invasive route compared with standard treatment. Conclusions: In the ASCO framework, merits in treatment schedule or route of administration may not be fully captured, and the test treatments in some non-inferiority trials showed negative NHB. It is desirable to assess not only NHB but also such merits in considering the risk-benefit balance in non-inferiority trials.
Expanding indications of existing drugs and associated costs under risk reimbursement models.
Authors: Page Ray D. , Ellis Peter G. , Lokay Kathleen , Barry Amanda 
Published: September 2018

e18306 Background: New payment models in oncology will likely include taking risk on drug costs. While new drugs could be excluded, existing drugs with expanded indications are problematic as the payer has limited data needed to exclude these costs. Recent label expansion for pembrolizumab (PB) in 1st line NSCLC for > 50% PD-L1 expression is an example of this risk. A broader indication in the future will likely result in use of PB for almost all 1stline patients. Methods: We reviewed treatment starts documented by providers in the Via Portal (VP) for 1st, maintenance (MT) and 2nd lines of therapy in non-squamous mutation-negative NSCLC for the 12 months ended 11/30/16. We assumed 6 month treatment lengths and calculated cost to Medicare (MC). We calculated a hypothetical alternative where PB received full 1st line and maintenance indication given with pemetrexed (PM) and carboplatin (per recent FDA filing and results of KEYNOTE-021 trial1). We assumed 2nd line patients received either docetaxel or ramucirumab/docetaxel (using 3rd line treatments in VP). Results: Total MC cost in the actual arm (n = 208) was $13,943,412, $12,190,264 and $11,614,488 for 1st, MT and 2nd line, respectively. The total MC cost in the hypothetical arm (n = 208) was $25,477,452, $25,687,168 and $6,415,575 for 1st, MT and 2ndline, respectively. This represents a total increase of $19,832,031 (52.5%) or $95,346 per patient. Conclusions: Bundled rates and shared savings that include oncology drugs are subject to significant financial risk for providers when existing drugs receive expanded indications to a new, larger population of patients. Langer CJ, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497-1508.
Economic aspects of nivolumab in non-small cell lung cancer (NSCLC): Lessons from real life.
Authors: Dudnik Elizabeth , Roisman Laila , Bar Jair , Peled Nir , Hammerman Ariel , Daher Sameh , Moskovitz Mor Tal , Shamai Sivan , Hanovich Ekaterina , Zer Alona , Merimsky Ofer , Wollner Mira ,   Israeli Lung Cancer Group
Published: September 2018

e18322 Background: Novel immunotherapy agents' costs have a significant impact on healthcare system budgets. Aside from the cost per dose of the compound, the total treatment cost (TTC) is affected by the duration of treatment (DOT). DOT in real life may differ significantly from that observed in the randomized clinical trials because of the differences in baseline patient characteristics and treatment patterns. Methods: Advanced NSCLC patients (pts) (n=192) treated with nivolumab 3mg/kg q2w (expanded access program/standard of care) at five Israeli cancer centers between January 2015 and March 2016 were included in the analysis. DOT and TTC were assessed in 2 groups (group A: ECOG PS 0/1, n=92; group B: ECOG PS ≥2, n=100). In addition, response for a subgroup of 49 pts was evaluated by RECIST, v.1.1. In this subgroup, DOT and TTC of treatment (Tx) beyond progression (PD) were assessed as well. Nivolumab cost per dose was calculated for a 78 kg pt based on current market price in Israel: 3 mg/kg X 78 kg = 240 mg = 11,250 NIS (2,993 USD). Results: Pt baseline characteristics: median age 67y (range, 41-99); males 68%; smokers 77%; ECOG PS ≥2 52%; Non-squamous/Squamous/NA 78%/19%/3%. 27% of pts continued nivolumab at the time of last follow-up. DOT and TTC are presented in the table below. Conclusions: DOT and TTC are similar for ECOG PS 0/1 and ECOG PS ≥2 pts. Tx beyond PD increases the TTC by 32%. These facts should be taken into consideration when evaluating budget impact of novel immunotherapy agents' implementation into routine practice. [Table: see text]
Nivolumab in the treatment of metastatic renal cell carcinoma: A cost-utility analysis.
Authors: Raphael Jacques , Sun Zhuolu , Bjarnason Georg A. , Sander Beate , Naimark David M 
Published: September 2018

e18331 Background: Nivolumab was recently shown to improve overall survival (OS) and health-related quality of life compared to Everolimus in metastatic renal cell carcinoma (mRCC) patients previously treated with antiangiogenic therapies (CheckMate-025 trial). The aim of this study is to assess the cost-utility of Nivolumab versus Everolimus from the perspective of the Canadian publicly funded healthcare system. Methods: To evaluate the cost-utility of Nivolumab versus Everolimus, a Markov cohort model that incorporated data from the phase 3 CheckMate-025 trial and other sources was developed. The outcomes of interest were healthcare costs, life-months and quality-adjusted life-months (QALMs) gained with Nivolumab as well as the incremental cost-effectiveness ratio (ICER), and the incremental net monetary benefit. A lifetime time horizon was used in the base case with costs and outcomes discounted 5% annually. The probabilities of progression and death from cancer and utility values were captured from the CheckMate-025 trial. Expected costs were based on Ontario fees and other sources. Scenario and sensitivity analyses (SAs) were conducted to assess uncertainty. Results: Compared to Everolimus, treatment with Nivolumab provided an additional 3.9 QALMs at an incremental cost of 33,386 Canadian dollars (CAD). The resulting ICER was 8,608CAD per QALM gained. With a willingness-to-pay (WTP) of 50,000CAD per Quality-adjusted life-year (QALY) ( = 4,167CAD per QALM), Nivolumab was not cost-effective in the base case. In one-way SAs, Nivolumab cost, median OS and treatment duration on Nivolumab were sensitive to changes with plausible threshold values. Assuming a WTP of 100,000CAD per QALY ( = 8,334CAD per QALM) and a scenario of Nivolumab cost with no drug wastage, Nivolumab became a cost-effective strategy with an ICER of 7,881CAD per QALM. Conclusions: With its current price , Nivolumab is unlikely to be cost-effective compared with Everolimus for previously treated mRCC patients from a Canadian healthcare payer perspective. While mRCC patients derive a meaningful clinical benefit from Nivolumab, considerations should be given to reduce drug wastage and increase the WTP threshold to render this strategy more affordable.
Risk-adjustment models for breast, lung, and colorectal cancer cost, utilization, and outcomes in a commercially insured population.
Authors: Sagar Bhuvana , Lin Yu Shen , Castel Liana Desharnais 
Published: September 2018

e18340 Background: Advances in oncology have led to rising costs which are unsustainable, necessitating value-based arrangements that maximize quality and overall outcomes. Our objective was to identify clinical and patient factors that predict higher costs and utilization among breast, lung, and colorectal cancer in a commercial population. Methods: We conducted a longitudinal analysis of claims in a sample of 9,748 commercially insured patients with breast, lung, and colorectal cancer, to measure costs and utilization based on presence of metastases, proxies for clinical biomarkers, patient demographics, and treatments. Results: Episode Risk Group (ERG) risk score, metastasis, and facility provider affiliation were cost drivers for all three types of cancer (breast, lung, and colorectal). Hypertension and younger age were cost drivers for breast cancer. In addition, HER2 positive status (β = 68,946, SE = 2,104, p < .0001) was significant in breast cancer, and VEGF in both lung (β = 56,975, SE = 10,138, p < .0001) and colorectal (β = 24,400, SE = 5,671, p < .0001) cancers. Metastasis also was associated with greater hospital admissions and hospital length of stay in all three cancers. Chemotherapy and supportive drug therapies accounted for the highest proportions of total medical costs among beneficiaries observed. Conclusions: Value-based reimbursement models in oncology should appropriately risk adjust by accounting for key cost drivers. Although claims-based methodologies may be further augmented with clinical data, we recommend adjusting for the factors we identified in models to predict costs and outcomes in breast, lung, and colorectal cancers.
Overall survival (OS) and stem cell transplant (SCT) in patients with FLT3 mutations treated with CPX-351 versus 7+3: Subgroup analysis of a phase III study of older adults with newly diagnosed, high-risk acute myeloid leukemia (AML).
Authors: Medeiros Bruno C. , Hogge Donna , Newell Laura F. , Bixby Dale L. , Solomon Scott R. , Strickland Stephen Anthony , Lin Tara L. , Erba Harry Paul , Powell Bayard L. , Podoltsev Nikolai Alexandrovich , Ryan Robert , Chiarella Michael , Louie Arthur , Lancet Jeffrey E. 
Published: September 2018

e18507 Background: FLT3+ AML patients (pts; 20%-30% of AML pts) often have rapid post-induction relapse, highlighting the need for therapies that improve the bridge to SCT. CPX-351 is a liposomal formulation that delivers a synergistic 5:1 molar ratio of cytarabine (C) and daunorubicin (D). CPX-351 demonstrated efficacy versus 7+3 in a randomized, open-label, controlled phase III trial in pts aged 60-75 years with newly diagnosed, high-risk AML; our analysis investigated outcomes in the subset of FLT3+ pts. Methods: Pts were randomized 1:1 to induction with 1-2 cycles of CPX-351 (100 u/m2 [C 100 mg/m2 + D 44 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/day x 7 days [2nd induction: x 5 days] + D 60 mg/m2on Days 1, 2, and 3 [2nd induction: Days 1 and 2]). Pts with complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 consolidation cycles. Results: Of the pts who had FLT3 mutations assessed and received study treatment, 22/138 (16%) pts in the CPX-351 arm and 20/136 (15%) pts in the 7+3 arm had baseline FLT3 mutations. AML subtypes in FLT3+ pts were: tAML (19%); AML after MDS with (38%) or without (10%) prior hypomethylating agents; AML after CMMoL (12%); and de novo AML with MDS karyotype (21%). In FLT3+ pts, median OS was longer with CPX-351 (10.25 mo) versus 7+3 (4.55 mo; HR = 0.57 [95% CI: 0.24, 1.33]; P= 0.093) and the rate of CR+CRi was higher (68% vs 25%). A greater number of FLT3+ pts treated with CPX-351 were able to undergo SCT (n = 10/22 [45%]; 4 pts were alive as of this analysis, after a median post-SCT follow up of 692 days [range: 96-769]) compared with 7+3 (n = 2/20 [10%]; neither pt still alive). The on-study safety profile of CPX-351 in FLT3+ pts was comparable to 7+3 and consistent with the overall study population. Serious adverse events were experienced by 7 (32%) FLT3+ pts in the CPX-351 arm and 10 (50%) in the 7+3 arm. Conclusions: CPX-351 demonstrated numerical improvement in median OS in older pts with newly diagnosed, FLT3+ high-risk AML and allowed more pts to undergo SCT. The analysis was limited by small number of pts. Clinical trial information: NCT01696084.
Real world patient numbers for AML targeted therapies.
Authors: dos Santos Marcos Tadeu , Smart Dave , Aita Eloise , Krein Peter Mark , Clark Jordan 
Published: September 2018

e18510 Background: The standard of care for AML patients (pts) has not changed in 40 yrs. Molecular biomarkers FLT3 and IDH1/2 are being tested for prognosis and risk stratification and recent trial results show these will be effective for targeted therapies. We analyzed real world data from a leading clinical lab (BioReference Laboratories Inc) to evaluate the frequency of pts eligible for FLT3 and IDH therapies. Methods: FLT3 (ITD/TKD), IDH1 and IDH2 mutation status results from 384 AML patients from Mar 2015 - Dec 2016, tested by a validated NGS assay, OnkoSight™, were analyzed and frequencies compared with the literature. Results: Of 384 AML pts from 31 US States, 52 were FLT3+ (13.5%, expected (exp) 24-38%). We observed 41 IDH+ pts (10.7%, exp 8-18%), with 27 pts IDH2+ (7%, exp 8-9%) and 13 pts IDH1+ (3.4%, exp 9%). Mutations in both FLT3 and IDH were found in 10 pts (2.6% of AML pts, exp 9%). This equates to 19.2% of FLT3+ pts (exp 31%), 15.4% of IDH2+ pts (exp 26%) and 1.9% of IDH1+ pts (exp 5%). We identified 1 pt harboring an unexpected triple positive (FLT3, IDH1 & 2) as IDH1 and 2 are considered mutually exclusive. Medicare was the single biggest payer (42%). Tests were requested by community based physicians in 92% of cases. Conclusions: The data suggest fewer pts may be eligible for FLT3 and IDH therapies in a real world setting than expected from the literature, possibly due to published data usually coming from cohorts of well characterized, filtered AML pts from research projects and/or clinical trials, which may not represent routine clinical testing. We find a lower level of FTL3 and IDH mutation overlap showing approx only 3% of all AML pts as eligible for at least two options of targeted therapies (exp 9%). [Table: see text]
Hematopoietic cell transplant comorbidity index (HCT-CI) to assess AML induction risk.
Authors: Schoen Martin W. , Mohammed Kahee A. , Freter Carl , Lionberger Jack M 
Published: September 2018

e18519 Background: Induction therapy for acute myeloid leukemia (AML) is intense and methods for risk appraisal of therapy are controversial. Formal comorbidity assessment may allow for improved prognostication in addition to age. The HCT-CI(+/-Age) was developed to inform risk of patients undergoing stem cell transplant, and has found use in predicting early outcomes in AML induction. We applied HCT-CI retrospectively to our experience to analyze the predictive power regarding patient survival during induction. Methods: 140 cases induced with idarubicin and cytarabine (IA) or IA plus cladribine (IAC) between Jan 2008 and Sept 2015. HCT-CI (+/- Age) was derived from information available prior to chemotherapy and NCCN Leukemia Risk were calculated. Death prior to discharge from the initial induction hospitalization was the primary outcome for logistic regression. Results: 107 patients received IAC and 33 IA with mean age of 57 and 66 years respectively (p<0.01). Regimen did not predict death (p=0.27). Median age was 61 (range 20-86) with mean scores of 2.0±0.2 (HCT-CI) and 2.9±0.2 (HCT-CI+Age). In univariate analysis HCT-CI (+/-Age) predicted death during induction. In multivariate analyses, when HCT-CI (+/-Age) was adjusted for (NCCN risk and regimen) or (age and regimen) predictive power was maintained (Table). Conclusions: These data suggest that HCT-CI predicts death during induction of AML and age did not augment prediction, up to age 70. We conclude that HCT-CI(+/-Age) may be a more useful tool than age alone or clinical instinct to help patients and providers make difficult decisions about therapy. [Table: see text]