bluuebunny/crossref_metadata_2025_split huggingface dataset:
A weighted criterion-based approach to value assessment of oncology drugs.
Authors: Ezeife Doreen Anuli , Cusano Ellen R. , Fares Aline Fusco , Sung Mike , Dionne Francois , Mitton Craig , Earle Craig , Chan Kelvin K. , Leighl Natasha B. 
Published: May 2019

6627 Background: The rising cost of anti-cancer therapy has motivated recent efforts to quantify the overall value of new cancer treatments. Multi-criteria decision analysis offers a novel approach to establish an explicit framework to evaluate new cancer treatments. Methods: We recruited a diverse multi-stakeholder group who identified and weighted key criteria to establish the Drug Assessment Framework (DAF). Strength of evidence (SOE) modifiers deducted points for lower quality evidence. Through one-on-one meetings with stakeholders, face and content validity of the DAF were established in an iterative process. Construct validity assessed the degree to which DAF scores were associated with the pan-Canadian oncology drug review (pCODR) funding decisions and European Society for Medical Oncology Magnitude of Clinical Benefit score (ESMO-MCBS, version 1.1). Sensitivity analyses were performed on the final results. Results: The final validated DAF includes ten criteria: overall survival, progression-free survival, response rate, quality-of-life, toxicity, unmet need, equity, feasibility, disease severity and caregiver well-being. The first five clinical benefit criteria represent 64% of the total weight. DAF scores range from 0 to 300, reflecting both the expected impact of the drug and the quality of the supporting evidence. When the DAF was retrospectively applied to the last 60 drugs (in blinded fashion) reviewed by pCODR (2015-2018), the mean total DAF score was 94 (range, 18-179). Drugs with positive pCODR funding recommendation had higher DAF scores than drugs not recommended for reimbursement (103 vs. 63, t-test p = 0.0007). Funded drugs had fewer SOE points deducted than those that were not funded (median 0 vs. 24 points deducted, Wilcoxon p = 0.03). The correlation coefficient for DAF and ESMO-MCBS was 0.37 (95% CI, 0.10 to 0.59). Sensitivity analyses that varied the subjective criteria either positively or negatively did not change the results. Conclusions: Using a structured and explicit approach, a criterion-based valuation framework was designed and validated. The DAF can provide a transparent and consistent method to value and prioritize cancer drugs, in order to facilitate the delivery of affordable cancer care.
Clinical and economic outcomes of pegfilgrastim in metastatic colorectal cancer.
Authors: Wilfong Lalan S. , Garey Jody S. , He Bo , Hayes Jad , Ives Hope , Hoang Susan Nga , Neubauer Marcus A. 
Published: May 2019

6636 Background: Febrile neutropenia (FN) resulting from myelosuppressive chemotherapy can lead to increased hospitalizations and mortality. Pegfilgrastim can be used to reduce the risk of FN; however, few studies address pegfilgrastim’s value in patients with metastatic solid tumors. This observational study compared outcomes for pegfilgrastim-treated (peg-tx) and peg-untreated (no peg) patients with metastatic colorectal (CRC) at US Oncology practices (USO) participating in the Oncology Care Model. Methods: Patients with metastatic CRC treated at USO from July 1, 2013 – December 31, 2014 and a qualifying baseline OCM episode were included. Propensity scoring was used to match (1:2) peg-tx and no peg cohorts based on line of therapy, number of comorbidities, age, gender, ECOG performance status, chemotherapy neutropenic fever risk, and dose reduction. Outcomes assessed included all-cause and infection-related hospitalization rates; total cost of care per 6-month OCM episode; and overall survival (OS). Results: Matched peg-tx and no peg samples were 149:298. The all-cause hospitalization rate was higher in the peg-tx vs. no peg population, 45% vs. 32% (OR 1.7, (1.1, 2.5), p = 0.011). Infection-related hospitalization rates were no different in peg-tx vs. no peg cohorts, p = 0.367. Cost of care was significantly higher for peg-tx patients vs. no peg ($58,787 ± $20,490 vs. $37,811 ± $19,593 respectively, p < .001). OS was 19.5 months (peg-tx) vs. 19.7 months (no peg), p = 0.882. Conclusions: While peg use in curative treatment settings for high risk patients is standard of care, in our Medicare population use in metastatic CRC did not result in a lower all-cause or infection-related hospitalization rate or impact in OS. There was a higher 6-month total cost of care associated with those patients who received peg during chemotherapy.
Desire to address costs at time of treatment decisions among patients with metastatic breast cancer.
Authors: Lei Yvonne Y. , Quain Katharine M. , Dizon Don S. , Jimenez Rachel , Shin Jennifer Adrienne , Sepucha Karen , Perez Giselle Katiria , Peppercorn Jeffrey M. 
Published: May 2019

6640 Background: Costs of cancer care may impact access to therapy, adherence, and distress among patients. However, the degree to which patients with metastatic breast cancer (MBC) wish to discuss financial issues when making treatment decisions is unknown. Methods: In a single arm feasibility trial, 40 women with newly diagnosed or progressive MBC completed a 1-page survey regarding goals and priorities for discussion with the oncology team. The survey included 17 potential priorities for discussion in the domains: treatment options, symptom management, emotional concerns, planning for the future, and lifestyle. We evaluated participants’ interest in prioritizing discussion of financial issues and sociodemographic and clinical correlates of this preference. We examined the relationship between desire to discuss financial issues and both distress on the Distress Thermometer (DT) and satisfaction with cancer care using Fisher’s exact test. Results: Among 40 participants, 11 (28%) reported interest in discussing financial issues when making treatment decisions, 29 (72%) were not interested. Average age was 57 (range 31-73), and the majority were white (85%) and college graduates (66%). Only 18% of white patients were interested in addressing cost, while 83% of non-white patients were interested (p < 0.01). Those with a college education were less likely to prioritize financial discussion compared to no college (16% vs. 47%, p = 0.04). Patients interested in discussing cost were more likely to have a household income < $50,000 (50% vs. 22% > $50,000, n.s.) and to have Medicaid (50% vs. 25% other insurance, n.s.). Additionally, patients with higher levels of distress (35% vs. 21% DT < 4, n.s.) and those on novel targeted or biologic therapy (42% vs. 21% other therapy, n.s.) were more likely to prioritize discussion of costs. Desire to discuss cost was not related to satisfaction with care. Conclusions: A substantial minority of patients with MBC, particularly those from less advantaged backgrounds, wish to discuss financial issues at time of treatment decisions. Financial toxicity research should recognize that not all patients desire this discussion and evaluate methods to screen for financial concerns and barriers to care.
Cost-minimization analysis for biosimilar pegfilgrastim in the prophylaxis of chemotherapy induced (febrile) neutropenia and expanded access based on budget neutral basis.
Authors: Wang Weijia , Balu Sanjeev , Campbell Kim 
Published: May 2019

6645 Background: Pegfilgrastim (pegfil) injection is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Assuming biosimilarity of biosim-pegfil and pegfil in the prevention of febrile neutropenia, we estimated cost minimization of conversion from pegfil to biosim-pegfil and subsequent potential expanded access due to cost savings. Methods: A cost minimization model was conducted based on a hypothetical panel of 20,000 patients using average selling price (ASP) for one chemotherapy cycle. ASP was obtained from 1Q 2019 payment allowance limits. The simulation included two steps: 1) cost minimization was calculated per cycle (biosim-pegfil and pegfil is administered 1 dose per cycle) when patients were converted to biosim-pegfil from pegfil on ratio of 10% to 100% at 10% intervals and at a discount from 15% to 35% at 5% intervals, and 2) expanded access to biosim-pegfil was calculated based on budget neutrality. Since pegfil has two forms of availability (Neulasta and Neulasta-Onpro) with the same price, results were to either conversion scenario. Results: Per-cycle per-patient cost minimization from converting pegfil to biosim-pegfil ranged from $702.27 (15% discount) to $1,638.63 (35% discount). For 20,000 patients, this yields savings of over $14 million (15% discount) to $32 million (35% discount) at 100% conversion rate. When half the patients were converted to biosim-pegfil, savings could range from > $7 million (15% discount) to > $16 million (35% discount). With 100% conversion rate and 15% discount, 3,529 additional patients could be treated with the savings generated. At 50% conversion rate, cost savings could be applied to another 1,765 patients with 15% discount, 3,333 patients with 25% discount, and 5,385 patients with 35% discount, respectively. Conclusions: Conversion from pegfil to biosim-pegfil can lead to potential cost savings and these savings can be applied to offer increased access to supportive care with biosim-pegfil for patients receiving chemotherapy on a budget-neutral basis. For payers with larger populations, savings can be substantial. More studies are warranted to evaluate such potential cost savings due to use of biosim-pegfil over reference pegfil.
Scope of practice of advanced practice providers (APP) in US community oncology.
Authors: Klink Andrew , Bapat Bela , Smith Yolaine , Nabhan Chadi , Feinberg Bruce A. 
Published: May 2019

6646 Background: Oncology practices are increasingly employing nurse practitioners (NPs) and physician assistants (PAs) known collectively as advanced practice providers (APPs) to improve practice workflow, increase efficiency, and enable physicians to focus on complex patient care. Understanding variations in scope of practice for APPs may help establish a benchmark against which future changes are measured. Methods: US community physicians responded to a web-based survey from Sep to Nov 2018. Physicians were asked how frequently their APPs performed certain tasks on a 5-point scale (i.e., never, occasionally, sometimes, frequently, and always). Responses have been summarized using descriptive statistics. Results: In this study, 163 physicians were surveyed, most (81.0%, n = 132) used APPs in their practice. Among physicians using APPs, 91.7% (n = 121) used NPs and 49.2% (n = 65) used PAs. Most physicians stated that APPs were frequently/always involved in providing patient education (84.1%), ordering imaging and laboratory studies (68.9%), and/or making supportive care decisions (62.1%). Over 85% (57.6%-59.8% occasionally/sometimes; 28.0%-28.8% frequently/always) of physicians agreed that APPs discussed imaging reports and end of life (EOL) care (57.6% occasionally/sometimes, 28.8% frequently/always) with patients. Regarding procedures: 51.9% (28.0% occasionally/sometimes; 24.1% frequently/always) responded that APPs performed bone marrow biopsies and intrathecal chemotherapy. Regarding systemic therapy: 68.2% (58.3% occasionally/ sometimes; 9.8% frequently) allowed APPs to modify existing regimen e.g., dose/schedule change; 39.4% responded that APPs made decisions about new therapy selection. Conclusions: While substantial variation in the role of APPs in community oncology practices was observed, similar themes emerged. APPs appear to be integral in patient education, ordering laboratory and imaging studies, and discussing EOL care. Fewer are involved in managing and selecting supportive care and systemic therapy. Longitudinal and longer follow up are warranted to ascertain whether the scope of these practices change over time.
National cancer expenditure analysis in the United States Medicare population, 2013.
Authors: Ruiz Emily S , Seiger Kira , Mostaghimi Arash , Schmults Chrysalyne 
Published: May 2019

6647 Background: Cancer is the second leading killer in the United States, but there is no comprehensive analysis evaluating total cancer costs by cancer and treatment modality. Methods: Data from the 2013 inpatient (100%), outpatient (100%), and carrier (5%) Medicare Limited Data Set Standard Analytic Files were queried for claims filed for International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for all cancer diagnoses. Claims associated with the ICD-9 codes for professional fees were analyzed by Current Procedure Terminology (CPT) code to determine resource allocation by disease. Outpatient oral chemotherapy costs were obtained from the National Average Drug Acquisition Cost database for 50 drugs used for cancer treatment in 2013. Results: $27.9 billion was spent on cancer treatment of which $12 billion (43%), $6.5 billion (23%), and $1.1 billion (4%) was allocated to professional, inpatient facility, and outpatient facility fees, respectively. Oral and hospital-based chemotherapy accounted for 17% ($4.7 billion) and 15% ($4.3 billion) of all cancer costs, respectively. Lung/thoracic cancer ($2.9 billion) had the highest total annual cost and multiple myeloma ($9,019, SD $19,962) is the most expensive cancers to treat annually per patient. Average out-of-pocket expenses are $470 (SD 287), which is 12% of the annualized per patient costs. Conclusions: In 2013, cancer accounted for only 5% of Medicare spending. Chemotherapy costs accounted for approximately a third of total spending and are likely to rise as innovation continues. Out-of-pocket spending can place a financial burden on cancer patients requiring more expensive treatments.
Phase 3 international trial of adjuvant whole brain radiotherapy (WBRT) or observation (Obs) following local treatment of 1-3 melanoma brain metastases (MBMs).
Authors: Fogarty Gerald , Dolven-Jacobsen Kari , Morton Rachael L. , Hruby George , Nowak Anna K. , Vardy Janette L. , Drummond Katharine J. , Dhillon Haryana M. , Mandel Catherine , Scolyer Richard A. , Shivalingham Brindha , Middleton Mark R. , Burmeister Bryan H. , Lo Serigne , Reisse Claudius H. , Paton Elizabeth J. , Steel Victoria , Williams Narelle C. , Thompson John F. , Hong Angela M. 
Published: May 2019

9500 Background: The role of adjuvant WBRT in MBMs is controversial. This trial compares WBRT with Obs after local treatment of 1-3 MBMs. Methods: The primary endpoint is distant intracranial failure (DIF) within 12 months of randomization. The a priori neurocognitive function (NCF) endpoint is Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall at 4 months. Secondary endpoints include local failure (LF), overall survival (OS) and global quality of life (QoL). Analyses were conducted on intention-to-treat basis with nominal two-sided significance level 5%. Drug therapy was allowed. Effective drugs became available during trial and their impact was analysed. Results: Of 586 eligible patients (pts), 215 consented from 31 sites in 3 countries (Australia, UK and Norway) between 2009 and 2017. Eight (0.04%) who withdrew or had no data collected were excluded. 107 randomized to Obs and 100 to WBRT. Mean age 62 years, 67% males, 61% with single MBM of mean size 2cm, 67% had extracranial disease at randomization. The two arms were well matched. NCF was completed by English speakers; 50 WBRT and 70 Obs at baseline, declining to 26 and 35 respectively at 4 months. Within 12 months, 54 (50.5%) Obs had DIF compared with 42 (42.0%) WBRT pts (OR 0.71; 95%CI 0.41-1.23; p = 0.222). There was no difference in LF (p = 0.100) or OS (log-rank p = 0.861). 53% (Obs) and 59% (WBRT) pts were alive at 12 months. There was no significant between-group difference in mean intervention effect on global QoL (p = 0.083). Pts who received T-cell checkpoint inhibitors and/or mitogen-activated protein kinase (MAPK) pathway inhibitors and WBRT before or within 12 months of randomization had DIF rate 29% compared with Obs and no systemic therapy had 44%, but was not significant (p = 0.228). Obs had greater relative improvement from baseline in HVLT-R at every timepoint. At 4 months, Obs had 20.9% improvement from baseline in HVLT-R-delayed recall compared to 2.7% decline in WBRT; overall adjusted average intervention effect 23.6% (95%CI 9.0, 38.2; p = 0.0018). There was no difference in time to cognitive failure or in proportions with global cognitive impairment. Conclusion: This level one evidence shows WBRT does not improve outcomes in MBMs. This practice-changing trial justifies the recent move away from WBRT that occurred during the course of the trial. Clinical trial information: NCT01503827.
Correlates of overall survival (OS) in metastatic uveal melanoma (mUM) and a randomized trial of cabozantinib (cabo) versus chemotherapy (chemo).
Authors: Olson Daniel , Bao Riyue , Allred Jacob B , Strand Carrie , Zha Yuanyuan , Carll Timothy C. , Labadie Brian , Bastos Bruno R. , Butler Marcus O. , Munster Pamela N. , Schwartz Gary K. , Luke Jason J. 
Published: May 2019

9506 Background: Survival is poor in mUM and treatment options are limited. MET kinase is over-expressed on UM and the MET inhibitor cabo showed activity in an early trial. Methods: A091201 was a 2:1 randomized phase II study testing progression-free survival (PFS) of cabo (60 mg daily) vs chemo (DTIC/TMZ). We studied baseline metastatic tumor samples (n = 19; 1 lung, 18 liver) by whole exome sequencing (WES) and RNAseq. We correlated data with OS and made comparisons for mUM vs. primary tumors from TCGA (n = 80). Results: 46 patients were accrued with 96% and 63% with liver metastases and elevated LDH, respectively. Toxicities were similar to prior reports of cabo and chemo. The trial stopped at interim analysis due to no difference in PFS (p = 0.964; HR = 0.99) or OS (p = 0.580; HR = 1.21). WES showed tumor mutational burden of 46±4 (mean±SEM) and did not separate OS at 1 year (p = 0.14, two-sided Wilcoxon rank sum test) in A091201. Recurrent known mutations included GNAQ/11, SF3B1, BAP1; novel mutations included GOLGA6L10, PKD1L3, and FAM228B. Gene expression signatures differed significantly between A091201 and TCGA cohorts including MET signaling (p = 7.87e-22), T cell-inflamed (p = 0.004), homologous recombination deficiency (p = 0.004), proliferation (p = 0.009) and hypoxia (p = 5.2e-10) (two-sided Student’s t-test). Tumor immune cell enrichment analysis revealed significant differences with lower M1:M2 macrophage (p = 1.2e-10) and higher Tregs (p = 6.0E-21) in mUM relative to TCGA (two-sided Wilcoxon rank sum test). Epithelial-mesenchymal transition gene expression signature was significantly associated with worse OS in A091201 (p = 0.02) with angiogenesis signature trending toward significance (p = 0.21) (log-rank test). OS separated by differentially expressed genes with OS ≤ 1 year associating with increased expression of the angiogenesis/immune-associated molecule neuropilin 1. Conclusions: These results provide insights between primary and mUM indicating potential novel therapeutic approaches. Support: U10CA180821, U10CA180882, T32GM007019, Exelixis. https://acknowledgments.alliancefound.org ; Clinical trial information: NCT01835145.
Five-year analysis on the long-term effects of dabrafenib plus trametinib (D + T) in patients with BRAF V600–mutant unresectable or metastatic melanoma.
Authors: Nathan Paul D. , Robert Caroline , Grob Jean Jacques , Stroyakovskiy Daniil , Karaszewska Boguslawa , Hauschild Axel , Levchenko Eugeny , Chiarion Sileni Vanna , Schachter Jacob , Garbe Claus , Bondarenko Igor , Davies Michael A. , Ribas Antoni , Flaherty Keith , Burgess Paul , Tan Monique , Gasal Eduard , Schadendorf Dirk , Long Georgina V. 
Published: May 2019

9507 Background: First-line treatment with D+T demonstrated prolonged progression-free survival (PFS) and overall survival (OS) in patients with BRAF V600–mutant unresectable or metastatic melanoma. With 5 years of follow-up, we report survival and describe characteristics of patients in the phase 3 COMBI-d and COMBI-v trials with long-term benefit. Methods: Pooled 5-year landmark data for patients treated with D+T in the phase 3 COMBI-d (NCT01584648) and COMBI-v (NCT01597908) trials were analyzed. The trials enrolled patients with previously untreated BRAF V600E/K–mutant unresectable or metastatic melanoma. Patients received D 150 mg twice daily plus T 2 mg once daily vs either D + placebo (COMBI-d) or vemurafenib (COMBI-v). The primary endpoints were PFS in COMBI-d and OS in COMBI-v. Results: The pooled population included 563 patients who received D+T (COMBI-d, n = 211; COMBI-v, n = 352). Four- and 5-year PFS and OS rates were similar, suggesting a stabilization (4- and 5-year PFS, 21% [95% CI, 17%-24%] and 19% [95% CI, 15%-22%, respectively]; 4- and 5-year OS, 37% [95% CI, 33%-42%] and 34% [95% CI, 30%-38%], respectively). In patients with normal baseline lactate dehydrogenase (LDH) levels the 5-year PFS rate was 25% vs 8% in patients with elevated baseline LDH levels. Similarly, the 5-year OS rate was considerably higher in patients with normal baseline LDH levels vs those with elevated LDH levels at baseline (43% vs 16%). Among patients with normal baseline LDH levels and < 3 organ sites with metastases, the 5-year PFS and OS rates were 31% and 55%, respectively. In addition, exploratory analyses will be performed to characterize subgroup(s) of patients most likely to experience long-term benefit. Of 299 patients who received subsequent anticancer therapy following treatment with D+T, 151 (51%) received an anti–CTLA-4 therapy and 102 (34%) received an anti–PD-1 therapy. The safety profile of D+T was as previously reported, and no new safety signals were observed. No treatment-related deaths were reported. Conclusions: First-line treatment with D+T leads to durable long-term benefit in many patients with BRAF V600–mutant unresectable or metastatic melanoma. Clinical trial information: NCT01584648; NCT01597908.
FDA analysis of depth of response (DpR) and survival across 10 randomized controlled trials in patients with previously untreated unresectable or metastatic melanoma (UMM) by therapy type.
Authors: Osgood Christy , Mulkey Flora , Mishra-Kalyani Pallavi Shruti , Lemery Steven , Ward Ashley , Keegan Patricia , Sridhara Rajeshwari , Theoret Marc Robert , Pazdur Richard 
Published: May 2019

9508 Background: Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 may not capture the full spectrum of benefit that patients with melanoma derive from targeted kinase inhibitors (TKI) or immunotherapies. We explored the relationship between DpR and overall survival (OS) in patients treated with TKI (BRAF, MEK inhibitors), immunotherapy (antibodies targeting PD-1 or CTLA-4), or chemotherapy (dacarbazine or paclitaxel). Methods: Ten randomized controlled trials of patients with previously untreated UMM were pooled and evaluated by type of therapy. DpR was grouped by maximal tumor shrinkage (G0 = no shrinkage or increase, G1 = ≤25%, G2 = 26-50%, G3 = 51-75%, G4 = 76- < 100%, and G5 = 100%). We performed an exploratory analysis evaluating the association between DpR and OS using hazard ratios (HR) generated from a Cox proportional hazards model where maximal tumor shrinkage category was included as a time varying covariate. Results: There were 3778 patients evaluable for tumor response. The table displays the HR for OS by DpR group and therapy type. Estimated OS at 24m in patients with deep response ( > 75%; G4+G5) treated with TKI and immunotherapy was 69% and 92%, respectively, although many patients were censored. Conclusions: For patients with previously untreated UMM a larger DpR correlates with a longer OS, regardless of therapy type. Deep response ( > 75%) is associated with a high rate of estimated OS at 24 months in patients treated with immunotherapy. Analysis of DpR provides additional granularity of response data and may provide a more nuanced prediction of clinical outcome. [Table: see text]