bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to 'Choosing Wisely' recommendations for radiation therapy in a commercially insured breast cancer population.
Authors: Roth Joshua A. , McDougall Jean A. , Halasz Lia Moriguchi , Fedorenko Catherine R. , Sun Qin , Goulart Bernardo H. L. , Patel Shilpen A.
Published: September 2018

e18267

Background: ASTRO ‘Choosing Wisely recommendations’ (CWr) note radiation therapy (RT) interventions lacking evidence of benefit in cancer care. This study evaluates adherence to the 2013 CWr to ‘not routinely use intensity modulated radiotherapy (IMRT) to deliver whole breast radiotherapy as part of breast conservation therapy’ using a novel linkage between the Western WA Cancer Surveillance System (CSS) and claims from two large commercial insurance plans. No studies have evaluated adherence to this CWr in a commercial insurance setting. Methods: CSS records for first primary Stage I/II breast cancer cases (2008-2015) were linked with Premera Blue Cross and Regence Blue Shield claims. Included cases had coverage for ≥12-months before/after diagnosis (or until death), lumpectomy within 6 months of diagnosis, and RT within 6 months of lumpectomy. We used generalized estimating equations (GEE) to evaluate associations between demographic (age, race) and tumor (grade, laterality, diagnosis year) variables and use of IMRT vs conventional conformal RT within 1 year of diagnosis. Results: We identified 1,048 first primary Stage I/II breast cancer cases that met inclusion criteria. Mean age was 61, 91% were white, 52% were left-side cases. The non-adherent proportions are in the table below. In GEE analysis, only left-side cases (OR=6.4, p<0.001) and years of age (OR=1.03, p<0.01) were independently associated with IMRT use. Conclusions: Patients with IMRT vs. conventional conformal RT after lumpectomy may incur additional cost without commensurate clinical benefit. In the first study of adherence to a CWr against IMRT in this setting, we found that left-side cases were 6-fold more likely to be non-adherent vs right-side cases. This association suggests that IMRT is being used to reduce radiation dose to the heart, though not supported by evidence. Overall, the small non-adherent proportion before/after the CWr suggests alignment between guidelines and use of IMRT in Western WA. Future studies should evaluate IMRT use in other regions and develop strategies to improve CWr adherence in left-side cases. [Table: see text]
Faster approvals?: Trends in the use of FDA’s expedited approval programs for oncology medications.
Authors: Vadola Lisa Ambrosini , Pond Monique A , Winter-Vann Ann , Whitsell Robin
Published: September 2018

e18270

Background: With the importance of speed-to-market and addressing unmet needs, pharmaceutical companies have sought accelerated approvals through the Food and Drug Administration (FDA). Introduced with the FDA Safety and Innovation Act (FDASIA) of 2012, Breakthrough Therapy Designation (BTD) has become an important mechanism for approval of serious and life-threatening conditions that do not have adequate therapies. Notably, these pathways have been ill-understood by both pharmaceutical companies and health care providers. This study assessed how BTD and other FDA designations have played a role in the approval of oncology drug marketing applications and evaluated trends in the use of these regulatory pathways. Methods: We analyzed publicly available data on novel oncology drug approvals by the FDA from 2012-2016, including the 4 expedited programs for serious conditions (BTD, Accelerated Approval, Fast Track, and Priority Review). Results: Of the 43 novel oncology drugs approved by the FDA between 2012-2016, 42 used at least 1 of the expedited approval programs, including 65% that used ≥2 programs and 35% that used ≥3 programs. The BTD has been used by 15 of the 43 (35%) approved novel oncology drugs since 2012. The use of the BTD, Accelerated Approval pathway, and Priority Review designation among approved oncology drugs has generally increased each year from 2012-2016, while the use of the Fast Track designation has decreased over the same time period. Conclusions: Companies seeking oncology approvals often use more than one expediting strategy. Alone or in combinations, the BTD, Accelerated Approval, and Priority Review have been shown to play an increasingly important role in oncology drug development. Data collected between 2012-2016 suggest that use of BTD is growing more common, while use of the Fast Track designation has decreased among approved oncology drugs. Additional expedited approval programs have remained steady or increased since the FDA introduced BTD. Based on these observations, we anticipate use of the BTD, Accelerated Approval, and Priority Review designation will grow in future oncology drug applications.
Implementing pregnancy screening prior to chemotherapy: A quality improvement initiative.
Authors: Rogers Brittany Kayla , Kolarich Andrew , Markham Merry Jennifer
Published: September 2018

e18274

Background: ASCO’s QOPI sets standards for excellence in oncologic care. One standard is screening appropriate female patients for pregnancy prior to chemotherapy. No guidelines exist regarding screening protocols or timing. Prior data collection at our institution from 2012-2014 revealed that 35% of women of childbearing potential were screened prior to chemo, with medical oncology performing only 7% of screening. Less than half (48%) of those tests were ordered within 14 days prior to treatment start. Methods: A quality improvement (QI) intervention was implemented at UF Health outpatient infusion center on 8/15/16 based on the above data. A checkbox was added to the pre-chemo checklist used by infusion nurses. For eligible patients (women ages 18-55 without prior tubal ligation or hysterectomy), a point of care pregnancy test, included in standing orders, was recommended. We reviewed data for women who received outpatient chemo during 9/16-11/16 to determine rates of pregnancy screening (PS) after intervention. Results: 49 women, ages 18-55, of childbearing potential were identified and presented for 174 chemo cycles from 9/1/16 to 11/30/16. Of these, 15 (30.6%) received PS before chemo. Fifty pregnancy tests were ordered during this period; all were negative. Of the 50 tests, 42 (84%) were ordered by medical oncology, 3 (6%) by a surgical oncology, 3 (6%) by radiation oncology, and 1 (2%) by emergency medicine. Of the PS tests ordered by medical oncology, 64.2% were within 14 days of chemotherapy. Conclusions: In three months of QI intervention, PS prior to chemo increased from 7% to 30.6%. Screening was 13% in women older than 45, but higher in women age 25-34 (60%) and 35-44 (67%). Although the screening rate improved, it remains below our goal of 80%. Possible explanations for low rates are inclusion of postmenopausal women and those older than 50. Excluding these patients could reduce screening burden while identifying appropriate patients. [Table: see text]
Disease-management indicators to improve gastric and colorectal cancer control in the Colombian National Health System.
Authors: Valencia Omaira , Lopes Gilberto , Sánchez Quintero Patricia , Acuña Lizbeth , Gonzalez Jaime , Lopera Diego , Uribe Daniel , Pulido Diana
Published: September 2018

e18288

Background: Gastric (GC) and colorectal cancer (CRC) are major health problems worldwide due to their high incidence and lethality associated with late presentation. The aim of this study was to develop a set of clinical, quality and administrative measures, for gastric and colorectal cancer based on evidence to assist health care insurers, providers and policy makers in controlling these diseases in Colombia. Methods: A systematic evidence-based literature search was performed to identify the initial list of indicators, which were then selected and developed using an adaptation of the RAND/UCLA appropriateness method by a panel of multidisciplinary expert panels with expertise in CRC and GC care, quality and public health. The following institutions participated in the study: The Ministry of Health and its High Cost Disease Office, medical professional societies, National Health Institute, Institute of evaluation of technologies in health, health care insurers and providers. A total of 1589 cases of GC and 2025 of CRC from the national administrative cancer registry, representing all new cases of these diseases in the country in 2015, were used to define the viability of the proposed measures, which the involved parties developed taking in consideration the whole disease spectrum from diagnosis to treatment. Results: After reviewing relevant articles and holding an in-person expert discussion the panel generated an initial proposed set of 45 disease-management indicators. A total of 15 disease-management measures for CRC and 16 for GC were developed and approved by the expert panel after two rounds of discussion and voting; these are related to opportunities to improve time between diagnoses to treatment and also include measures assessing clinical outcomes and administrative processes. Conclusions: We developed disease-management indicators for GC and CRC in a consensus with healthcare system stakeholders that are feasible and applicable in Colombia. In time, through continuous efforts towards improving the quality of care provided, these will allow all parties to monitor and decrease the burden of GC and CRC in the country and may serve as a model to other low and middle income countries.
Racial differences in the financial impact of breast cancer.
Authors: Wheeler Stephanie B. , Spencer Jennifer , Pinheiro Laura C , Carey Lisa A. , Olshan Andrew F , Reeder-Hayes Katherine Elizabeth
Published: September 2018

e18293

Background: Racial variation in the adverse financial impact of cancer may contribute to observed differences in the initiation and completion of guideline-recommended adjuvant treatments. We describe racial differences in the financial impact of breast cancer diagnosis in a large, population-based, prospective cohort study. Methods: Patients were recruited via rapid case ascertainment through the North Carolina cancer registry as part of the Carolina Breast Cancer Study, with oversampling of black women and women younger than 50. Participants provided medical records and survey data on demographics, socioeconomic status, treatments, and financial impact of cancer. We used chi-square tests and multivariable logistic regression to understand racial differences in financial impact of breast cancer through 25 months post-diagnosis. Results: Our sample included 1,196 non-Hispanic blacks and 1,236 non-Hispanic whites. Since diagnosis, compared to white women, black women more often reported: any adverse financial impact of cancer (59% vs 39%, p < 0.0001); lost income (49% vs 35%, p < 0.0001); lost job due to cancer (13% vs 6%, p < 0.0001); financial barriers to treatment (24% vs 10%, p < 0.0001); transportation barriers to treatment (15% vs 3%, p < 0.0001); and lost health insurance (9% vs 3%, p < 0.0001). In multivariable models, black women had higher odds of: experiencing any adverse financial impact of cancer (Adjusted Odds Ratio [AOR]: 1.9 (1.6-2.3)); losing income (AOR: 1.5 (1.3-1.9)); losing their job (AOR: 2.1 (1.5-2.8)); experiencing financial barriers to treatment (AOR: 2.2 (1.7-2.9)); experiencing transportation barriers to treatment (AOR: 4.8 (3.2-7.1)); and losing their health insurance (AOR: 2.6 (1.7-4.1)). Conclusions: Compared to whites, black women with breast cancer experience significantly worse financial impact of cancer. Disproportionate financial strain may contribute to higher stress, lower treatment compliance, and worse outcomes, among black women. Efforts to alleviate the adverse financial impact of cancer treatment and to improve communication between patients and providers about potential financial distress may be particularly valuable for black women, due to their greater financial vulnerability.
Market capitalism in cancer pharmaceuticals.
Authors: Conter Henry Jacob
Published: September 2018

e18295

Background: How can health technology assessments be deployed in a market-based healthcare system to improve value and sustainability? Methods: The pan-Canadian Oncology Drug Review (pCODR) is an evidence-based, cancer drug review process that guides formulary decision-making. As of 1/1/17, data from all 98 reviews and economic guidances were abstracted for price of medication, total health care cost per patient, cost-utility provided by the submitter and re-analysis by pCODR. Regression analysis identified correlations. Expected use of therapy was estimated employing data from the Canadian Cancer Society. An optimal formulary was developed, optimizing value for money. Results: Of the 98 reviews, 13 were not finalized, 3 were withdrawn, 1 was suspended. 4 reviews were excluded since the base-case was ambiguous. The median drug price per 28-day cycle was $7,567 (range $2,800-$18,435), with no annual difference from 2012-2016 (p = 0.49). The median best-estimate of cost-utility was $190,858/QALY (IQR $125,585/QALY) with a median net increase in health system cost of $62,771/patient (IQR $89,260) and 0.48 LYG/patient (range 0.04-2.43). Cost per 28-day cycle was a weak predictor of value (R² = 0.02, p < 0.01), and not of health system cost (R² = 0.14, p = 0.06). Funding all efficacious medications by a single payer insurance plan in Canada would require $5.91 billion producing 31,705 QALYs, annually. 26% of the cumulative budget would buy 41% of the health benefit, 56% of the budget would buy 70% of the effect. Once a budget is determined, new medication would replace drugs of higher cost per QALY. Employing this method increased QALY yield of the budget by 67%, 21%, 15%, and 14% at $1B, $2B, $3B, and $4B, respectively. The formulary turnover would be 66%, 44%, 37%, and 22% at each respective budget level. Conclusions: An optimized formulary requires practical deployment of HTA, the ability to shift resources across budgets, and the ability to continuously renegotiate prices based on incremental value. Future work is needed on publically acceptable divestment methods for lower value pharmaceuticals.
Bridging the financial assistance gap: A pilot study of a patient-facing app to identify drug financial assistance programs.
Authors: Zafar Yousuf , Manners Ian , Nicolla Jonathan , Friedman Fred , Gagosian Ben , Pollak Kathryn I.
Published: September 2018

e18296

Background: Many cancer patients face high treatment-related costs and are often unaware of available financial resources. We designed “Bridge” as a stand-alone, smartphone app to reduce out-of-pocket treatment costs by connecting patients to tailored financial assistance programs. The goal of this pilot study was to evaluate the usability and preliminary effectiveness of Bridge. Methods: Eligible cancer patients were receiving anti-cancer treatment, owned a smartphone, and reported out-of-pocket treatment-related costs. Patients interacted with Bridge, inputted personal and financial data, and reviewed personalized financial resource results. Usability was assessed via the validated System Usability Scale (SUS). To be usable, patients would have to score at least 68 on the SUS. Effectiveness was assessed by two measures: “Bridge improved my knowledge about financial aspects of cancer care and what can be done about it” (1 = strongly disagree to 5 = strongly agree) and “Using this tool was helpful with my financial concerns” (1 = strongly disagree to 5 = strongly agree). Results: We enrolled 30 patients. 63% were female, 23% were non-white, 66% had greater than high school education, 97% were insured (48% Medicare), and 23% were employed. Median annual household income was $60,796. All patients completed a full interaction with the app, with median time to results of 116 seconds. 72% of patients matched to at least one currently open program, with patients matching to a median of 4 financial assistance programs. 90% of patients reported an SUS score of usable (i.e., > 68 out of 100). The median SUS score was 85. 83% of patients agreed or strongly agreed that “Bridge improved my knowledge about financial aspects of cancer care and what can be done about it.” 53% of patients agreed or strongly agreed that “Using this website was helpful with my financial concerns.” Conclusions: We found that patients rated Bridge as usable and acceptable. We also found that Bridge helped match most patients to relevant assistance programs and improved knowledge about financial aspects of cancer care. The next phase of this NCI-funded study will test the effectiveness of Bridge in a large, randomized, controlled trial.
Oncologists’ awareness, knowledge, and perceptions of value frameworks.
Authors: Wong William Bruce , Ravelo Arliene , DiBonaventura Marco , Shah-Manek Bijal
Published: September 2018

e18317

Background: The increasing prevalence of cancer coupled with approvals of new drugs and technologies have brought increased scrutiny to cost/benefit of treatments in oncology. To address the rising concern about oncology drug costs, several stakeholders have developed frameworks to help assess the value of oncology regimens. The objective of this study was to assess oncologists’ perceptions, awareness and knowledge of all oncology value frameworks in the US. Methods: Data were collected from an electronic cross-sectional survey of 200 US-based oncologists recruited from an online panel. Oncologists were asked about their knowledge and perceptions of four value frameworks – the National Comprehensive Cancer Network’s (NCCN) Evidence Blocks, American Society of Clinical Oncology (ASCO) Value Framework, Institute for Clinical and Economic Review (ICER) Value Framework and Memorial Sloan Kettering (MSK) Drug Abacus framework. Findings were reported descriptively. Results: Oncologists were most familiar with the NCCN Evidence Blocks (90%) followed by the ASCO Value Framework (84%), ICER value framework (57%) and Drug Abacus (56%). Among those that were familiar with the value frameworks, almost equal proportions found the NCCN Evidence Blocks vs. ASCO Value Framework to be “useful/very useful” (75% vs. 74%) followed by ICER Value Framework (64%) and Drug Abacus (56%). More than three out of four oncologists surveyed (76%) had used value frameworks in the past, with NCCN Evidence Blocks being used most often (61.5%) followed by ASCO Value Framework (48.4%), ICER Value Framework (21%) and Drug Abacus (15%). NCCN Evidence Blocks was ranked highest for its ease of use, comprehensiveness, feasibility for use in the clinical setting, ability of patients to understand and most favorable overall, followed by ASCO Value Framework, ICER Value Framework and Drug Abacus. Conclusions: The majority of oncologists were familiar with value frameworks and had used them in the past. Of the four oncology Value Frameworks, NCCN Evidence Blocks were perceived most favorably by oncologists followed by ASCO Value Framework.
Budget impact model (BIM) to evaluate treatment costs associated with variable utilization rates of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Drea Edward Joseph , Corman Shelby , Cockerham Alex R , Patel Miraj , Hudspeth Louis , Yu Andrew Kenneth
Published: September 2018

e18321

Background: Cabazitaxel (CBZ) is a microtubule inhibitor indicated in combination with prednisone for treatment of patients with mCRPC previously treated with a docetaxel (DOC)-containing regimen. Recently published results of the PROSELICA trial may provide the basis for changing utilization rates of CBZ. Methods: A BIM was developed to project the overall costs of varying utilization rates of post-DOC treatment modalities for the management of mCRPC. Treatment costs of two dosage schema for CBZ were compared to abiraterone acetate, enzalutamide, and radium-223. Prevalence of mCRPC was estimated using US Census and population modeling data. Medication costs were derived from published benchmarks; dosing/monitoring information from prescribing information; and duration of therapy from published trials. Rates and costs of Grade 3 / 4 adverse events (AEs) per published trials were also incorporated. Results: In a hypothetical 1 million member US health plan, 100 pts are estimated to receive 2nd line (2L) treatment for mCRPC. Reported utilization rates for 2L agents calculate to a PMPM of $0.623. Following publication of the PROSELICA study, modeling a potential increase in CBZ 20 mg/m2 utilization from 0% to 7% and modeling a 12% to 16% utilization rate change for CBZ 25 mg/m2, costs are projected to decrease by -$0.022 PMPM or $265,033 over a one year period. Although AE costs of management calculate higher for the CBZ doses, lower monitoring and drug acquisition costs contribute to account for these findings (Table 1). Conclusions: Increasing utilization rates of CBZ in 2L mCRPC can result in a slight cost decrease due to variation in CBZ dosing and AE rates, and lower monitoring and acquisition costs. [Table: see text]
Impact of breast cancer treatments on cancer clinic resource utilization.
Authors: Gopalakrishnan Dharmesh , Goraya Shazia Tanvir , Banjac Svetlana , Yanda Courtney , Abraham Jame , Grobmyer Stephen R. , Pederson Holly Jane
Published: September 2018

e18324

Background: Understanding clinic-based resource utilization among breast cancer (BC) patients is critical for the development of bundled payment models, and redesigning efficient value based systems of care delivery. BC outpatient visits (OVs) are costly from a time and human resource perspective and warrant investigation. Methods: This observational study included patients who were diagnosed with BC (Stages 0 to 3) in 2012 and were followed within our health network. Frequencies of OVs were compared between years 1, 2 and 3 of follow-up across subgroups, using one-sample Kolmogorov-Smirnov test; p < 0.05 was considered significant. Results: Of 643 patients identified, 83% were Caucasian and 99.5 % were females. 99.4% had breast surgery, 60% received radiation, and 42% received chemotherapy. 66% of patients who had mastectomy had reconstruction (73% implants, 27% tissue flap). The average duration of follow-up was 3.2 yrs. The frequency of OVs was highest in the 1st year after diagnosis across all groups in the Table (all p < 0.001). Breast reconstruction was associated with high clinic resource utilization; tissue flap procedures were associated with significantly more OVs than implant procedures during the 3 years (median of 16 vs.14 visits, p < 0.001). Conclusions: Outpatient visits represent a significant resource requirement associated with breast cancer care. These data are an important baseline as we design improved models of care and bundled payment models, and can be used to set expectations among breast cancer patients and care teams. [Table: see text]
Total 1-year cost of diffuse large B-cell lymphoma (DLBCL) beyond first line (1L) therapy: A retrospective cohort analysis.
Authors: Purdum Anna , Tieu Ryan , Reddy Sheila R. , Broder Michael
Published: September 2018

e18333

Background: This cohort study estimated cost and healthcare use among DLBCL patients who progressed beyond 1L therapy. Methods: Using the MarketScan database, patients ≥18 years old who had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) as 1L therapy and a claim for DLBCL (ICD-9-CM 200.7X) in the year before or 90 days after 1L start were selected for 2 cohorts: nonrelapsers who had no second line (2L) treatment for ≥2 years and 2L patients with non-R-CHOP chemotherapy after 1L. Patients not continuously enrolled for 6 months before and ≥2 years after 1L initiation, or those treated with maintenance rituximab or lenalidomide were excluded. 2L was subgrouped based on time between 1L end and 2L start: refractory (≤3 months), early (4-12 months), and late relapse (>12 months). Descriptive statistics compared cost and use between groups. Subsequent 2-year and 3-year data will be presented. Results: There were 217 (15.8%) 2L and 1,157 (84.2%) nonrelapse patients identified. Among 2L patients, 61 had hematopoietic stem cell transplant (HSCT) within 1 year. Of these HSCTs, 42.6% were early relapse patients vs. 24.6% late and 32.8% refractory (p=0.05). Mean total cost was $210,488 (SD $172,851) in 2L and $25,044 (SD $32,441) in non-relapsers (p<.001). Within 2L, mean total 1-yr cost was $232,796 in early relapse, $213,866 in late, and $191,079 in refractory (p=0.3314). For HSCT patients, cumulative 1-yr and 2-yr costs were $301,426 (Table) and $421,739. Conclusions: DLBCL treatment beyond 1L is resource intensive; chemotherapy and HSCT are major drivers of cost despite a low rate of HSCT. Cost in early relapsers may be higher than late relapsers or refractory patients due to higher transplant rates. [Table: see text]
Cost savings of conversion from filgrastim or pegfilgrastim to biosimilar filgrastim-sndz for chemotherapy-induced (febrile) neutropenia (CIN/FN) prophylaxis and expanded access to biosimilar GCSF on a budget neutral basis.
Authors: McBride Ali , Abraham Ivo , MacDonald Karen , Campbell Kim , Bikkina Mohan , Balu Sanjeev
Published: September 2018

e18334

Background: Biosimilar filgrastim (Zarxio) provides a more cost-efficient alternative to reference and pegylated filgrastim for CIN/FN prophylaxis. Using biosimilar conversion rates, we determined savings achieved, number needed to convert (NNC) to purchase additional Zarxio, and the incremental number (n) of patients (pts) that could be provided Zarxio on a budget neutral basis using various filgrastim cycle/treatments scenarios. Prior real-world practice studies have shown variations in GCSF duration including shorter durations (Weycker 2006; Gascon 2016) relative to registration trials and guideline recommendations. Methods: Calculations were done for a panel of 20000 pts; chemotherapy of 1 or 6 cycles with 5, 7 or 11 filgrastim injections; cost of medicines using average selling price (Zarxio $245.08, Neupogen $283.87, Neulasta $3761.22) and subcutaneous administration per Current Procedural Terminology ($42.31 hospital outpt). NNC is the n to be converted to Zarxio to purchase 1 additional Zarxio dose or the full regimen. This yielded the incremental n that could receive any of the 6 prophylaxis scenarios budget neutrally. Results: See table below. Conclusions: A 20000 pt panel yields expanded access to Zarxio, on a budget-neutral basis, to 2699 additional pts if 100% are converted from Neupogen; and to 4063 to 32939 additional pts, depending on cycles/treatments, if converted from Neulasta. Weycker et al, Ann Pharmacother 2006;40:402-7. Gascon et al, Support Care Cancer 2016;24:911-25. [Table: see text]
Cost-effectiveness of nivolumab in advanced renal cell carcinoma.
Authors: Sarfaty Michal , Leshno Moshe , Gordon Noa , Moore Assaf , Neiman Victoria , Rosenbaum Eli , Goldstein Daniel A.
Published: September 2018

e18338

Background: In recent years, new drugs have been introduced to the second line setting of advanced renal cell carcinoma (RCC). Nivolumab increases overall survival and is associated with less toxicity compared to everolimus in this setting based on the Checkmate 025 study. However, due to nivolumab's high cost there is a need to define its value by considering both efficacy and cost. The objective of this study was to estimate the cost-effectiveness of nivolumab for the second-line treatment of advanced RCC from the US payer perspective. Methods: A Markov model was developed to compare the costs and effectiveness of nivolumab with those of everolimus or placebo in the second-line treatment of advanced RCC. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2016. Model robustness was addressed in univariable and probabilistic sensitivity analyses. We addressed the controversial issue of the extensive duration of immunotherapy treatment amongst long term survivors, which may or may not be approved by payers. Results: The total mean cost per-patient of nivolumab versus everolimus was $101,070 and $50,935, respectfully. Nivolumab generated a gain of 0.24 LYs (0.34 QALYs) over everolimus and 0.89 LYs (0.96 QALYs) over placebo. The incremental cost-effectiveness ratio (ICER) for nivolumab was $146,532/QALY versus everolimus and $105,232/QALY versus placebo. Limiting the maximal treatment duration of nivolumab to two years lowered the ICER to $121,788/QALY versus everolimus and $96,418/QALY versus placebo. Conclusions: Our analysis established an ICER of $146,532/QALY for nivolumab versus everolimus in second-line advanced RCC treatment.
Comparison between real costs and patient's perceptions of the chemotherapy in a Brazilian cancer care facility.
Authors: Lorandi Vinicius , Debiasi Marcio , Stefani Stephen D. , Ribeiro Leticia , da Costa Marieni , Trevisan Bibiana
Published: September 2018

e18343

Background: Cancer is growing very fast and is responsible for roughly 7 million deaths annually. Cancer patients throughout the world suffer from both psychosocial and financial distress early in the time they are diagnosed with the disease. While anti-cancer therapy can magnify such effects by consuming extra intellectual energy from the patient and their family, further burden derived from the economic implications of cancer treatment have been ranked by many as an urgent issue. Methods: 46 patients with diagnosis of prostate, breast, lung or gastrintestinal cancer were asked to fill out a form while receiving chemotherapy. It contained 14 questions. Nurses were responsible for data collection. Wilcoxon test was used to test for interaction. Results: The mean age of patients was 62.2 (±13) and 58% of them were women. Aproximately half of them declared having completed higher education or more. The majority of patients had breast cancer (40%) followed by colorectal (38%), prostate (16%) and lung (5%). Most of the patients believed to be treating a localized disease and thought cure was their treatment goal. 31% of patients said they spent more than expected with their treatment and nearly half thought cost to be a concern. When reviewing patient's expectations and real treatment goals we noticed that the majority of patients had stage IV disease (56%) and that 60% were under palliative care. The median actual cost declared by patients was R$3,000 while the real cost median was R$7,055 which accounts for a 40% downstaging of the real cost. At last, 78% of patients estimated the costs to be less than it really is. Conclusions: There is still a large gap between patient's perceptions about chemotherapy goals and disease stage. When it comes to costs of the treatment the majority of patients tend to underestimate it. That may be in part because most brazilian private health care providers do not work with co-participation and therefore all costs are covered.
Effect of clinical outcome-driven reimburesement on cost savings and innovation in multiple myeloma.
Authors: Oren Ohad , Oren Michal
Published: September 2018

e18344

Background: The cost of cancer care is dissociated from the individual patient’s clinical outcome. A cancer patient treated with a particular drug incurs a fixed expense that is independent of her clinical response. Manufacturers thus have little incentive to design medications more effective than the minimum required for FDA approval. Methods: We propose a model whereby drug manufacturers are rewarded for sustained patient responses. Clinical information flowing to insurance companies dictates patients’ co-payment rates. “Integrated” PFS (iPFS) is defined as the mean of the median PFS of all medications approved for an indication. Patients with objective evidence of disease progression before reaching a given iPFS endure no out-of-pocket expenditure and insurance company deducts a certain percentage from launch price. Patients with durable responses longer than a chosen iPFS threshold pay 20% while the insurance company pays 80% of launch price. For each patient still responding at a specific (high) iPFS, drug company earns extra percentage of launch price via the insurance company (same fraction saved from cases of failure to respond). PFS Kaplan-Meier curves of five common drugs in mm were assessed. Model's impact was calculated. Results: The calculated iPFS was 17 months. iPFS thresholds chosen were 0.7 and 1.2, equaling 11.9 and 20.4 months. For each patient progressing before 11.9 months, the manufacturer were to (randomly) lose 19% of launch price. For each patient with no progression at 20.4 months, it was calculated that manufacturers should earn extra 15% of launch price to achieve overall financial neutrality. Patients had no out-of-pocket expenditure if they had progression earlier than 0.35 iPFS. Approximately 70k patients experienced early progression and were spared cost, with savings amounting 5 m dollars. Amgen and Bristol-Myers generated extra annual revenues amounting 18.4 and 10.6 m dollars for carfilzomib and elotuzumab. Celegne and Takeda experienced annual deductions of 9.9 and 25.9 m dollars for lenalidomide and bortezomib. Conclusions: Our model would spur scientific innovation while generating economic savings for mm patients.
Frequency of target attainment and toxicity with reduced PEG-asparaginase (PEG) dosing in acute lymphoblastic leukemia (ALL).
Authors: Streck Mitchell , Christ Trevor , Stock Wendy , Knoebel Randall
Published: September 2018

e18501

Background: Asparaginase (ASN) is a critical part of ALL therapy; however, in adults, a higher incidence of toxicities results in treatment delays and suboptimal exposure. We have reported a higher rate of PEG toxicity in pts > 50 yrs of age, baseline liver dysfunction, diabetes, and obesity (BMI ≥ 30). Thus, we hypothesized that reducing the PEG dose from 2500 units/m2 to 1000 units/m2 with further reduction to 500 units/m2 if any of those co-morbidities were present would reduce toxicities and still achieve therapeutic ASN levels. Methods: This is a single-center, retrospective study that included adult pts with ALL. Pts must have received at least one dose of PEG using a pediatric inspired regimen that includes 7 doses of PEG. The primary objective was to determine the rate of target ASN activity (≥ 0.1 IU/mL) one week after administration of reduced PEG during induction. Secondary objectives included the incidence of grade 3/4 toxicity based upon CTACE 4 criteria (hepatotoxicity, pancreatitis, hypertriglyceridemia, and VTE) between standard (SD) > 1000 units/m2 and reduced (RED) ≤1000 units/m2 PEG dosing. Results: 41 consecutive pts with ALL were included. Median age was 43 years (range 18-76). Median WBC upon admission was 7.6. At baseline, 25 pts (61%) had at least one comorbidity. 26 pts (63%) received SD PEG and 15 pts (37%) received RED PEG with median dose 1000 units/m2. 80% of pts achieved target ASN activity following administration of a RED PEG induction dose, median level of 0.1 IU/mL (IQR 0.1-0.24 IU/mL). 30 pts (73%) experienced grade 3/4 toxicity during induction, 81% in the SD group vs 60% in the RED group (p = 0.3). During induction, grade 3/4 hepatotoxicity was seen in 16 SD pts (62%) vs 6 RED pts (40%) (p = 0.211). Grade 3/4 hyperbilirubinemia was seen in 12 SD pts (46%) vs 1 RED pt (7%) (p = 0.014). Conclusions: The majority of pts attained a therapeutic ASN activity level with RED PEG. This resulted in a trend towards lower incidence of overall toxicity and a significant decrease in hyperbilirubinemia. A larger prospective study will be needed to determine whether decreased toxicity during induction correlates with fewer treatment delays, improved drug delivery, and better treatment outcome.
Cost of care for adult patients with relapsed acute lymphoblastic leukemia (rALL) in Germany.
Authors: Su Yun , Schmitter Sarah , Navarro Ana , Mayerhoff Lukas , Prieur Sigurd , Lehne Moritz , Loberiza Fausto Rodriguez
Published: September 2018

e18504

Background: Adult ALL is a rare but progressive frequently fatal disease. For those who survive and respond to initial therapy, many experience relapse. For relapse ALL (rALL), stem cell transplant (SCT) is potentially curative. This retrospective observational study investigates the cost of care and the impact of SCT on total cost for rALL. Methods: A representative sample of German claims data covering approximately 7 million of the German population was used to identify patients 18 years and older with a new diagnosis of ALL (ICD-10-GM code: C91.0*) between Jan 2011 and Dec 2015 who had a relapse after remission to initial treatment. Mean health care cost per patient per quarter were determined by whether or not SCT was received after relapse. Costs were from the perspective of German statutory health insurance and included prescription, outpatient and inpatient treatment costs. Results: Of the total 116 incident adult ALL patients identified, 29 (25%) were determined to have had a relapse, 11 underwent SCT after the relapse (38%). Patients with a SCT appear to incur higher cost than those without SCT in each of the quarters after relapse was diagnosed (Table), with the highest in the first quarter, but decreasing in subsequent quarters. Inpatient cost accounted for the majority of the cost for the first three quarters for both SCT and non-SCT patients (64% in Q2 to 86% in Q1). The number of patients in the SCT cohort remained relatively stable, while the non-SCT cohort had only half the patients left by the third quarter post relapse. Conclusions: Current results inform the magnitude of cost in Germany associated with adult patients with rALL with or without a SCT after relapse. It would be important to determine the magnitude of benefit such as long-term survival associated with SCT as well. The cost estimates provide a benchmark against which new treatment options for rALL can be compared. [Table: see text]
Efficacy of clofarabine and low-dose cytarabine combination for genetically high-risk acute myeloid leukemia prior to allogeneic stem cell transplantation.
Authors: Vigil Carlos Enrique , Jahan Nusrat , Paun Oana Valeria , Weis Jennifer , Heckman Kevin , De Magalhaes-Silverman Margarida , Carter Thomas H.
Published: September 2018

e18515

Background: The outcome of genetically high risk acute myeloid leukemia (AML) patients (pts) remains poor, with a median overall survival (OS) of a few months after the failure of regimens. Long-term survival requires complete remission followed by allogeneic stem cell transplantation (ASCT).Clofarabine, a deoxyadenosine analog, at 20mg/m2 days 1-5, in combination with low-dose cytarabine (LDAC) has reported efficacy and tolerability in older newly diagnosed AML pts (Cancer 2015;121:2375). We have therefore prioritized this combination for relapsed/refractory(R/R) pts. Aims:Determine the efficacy of Clofarabine and low dose cytarabine in R/R AML pts who are eligible for ASCT. Methods: Using Holden Comprehensive Cancer Center database, we performed a retrospective chart review on 16 pts of R/R AML who were treated with Clofarabine and LDAC between January 2014 and Dec 2016. Each patient received Clofarabine 20mg/m2on days 1-5 IV and LDAC on days 1-10 subcutaneous. The primary endpoint was complete remission (CR) or complete remission with incomplete marrow recovery (CRi). Secondary endpoint was median OS. Results: Sixteen pts were analyzed. The median age was 58 years (range 27-78). Nine pts (56%) had AML with high risk characteristics (complex karyotype and/or presence of FLT3-ITD). Nine pts achieved either a CR or CRi. Responses were observed in 7of 9 pts with genetically high-risk features. 2 pts had mutated TP53, and both of them achieved CR. The median OS time was 13.25 months (range 3.6-19.2 months). 4 pts received ASCT after treatment combination. Conclusions: These results suggest that Clofarabine is well-tolerated and effective in the treatment of R/R AML pts, especially those with high-risk genetics. Clofarabine and LDAC could be used as a bridging therapy prior to ASCT for high-risk R/R AML pts. Future clinical trials are warranted to explore additional modifications to this combination in order to optimize therapy for this group of high-risk and heavily treated R/R AML pts.
Flow cytometry minimal residual disease assessment in peripheral blood of adult acute lymphoblastic leukemia patients.
Authors: Minkovsky Alissa , Charest Karry , Schmidt Ryan , Briggs Debra , DeAngelo Daniel J. , Li Betty , Morgan Elizabeth , Pozdnyakova Olga
Published: September 2018

e18517

Background: Multiparametric flow cytometry (FC) of bone marrow aspirate (BM) is a widely used method of minimal residual disease (MRD) assessment in acute lymphoblastic leukemia (ALL). In practice, ALL with hematogone-like phenotype and patients with recurrence of isolated extramedullary disease present challenges in accurate determination of MRD status. We hypothesized that addition of FC MRD of peripheral blood would aid in the interpretation of MRD status. Methods: 76 matched BM and PB specimens were analyzed independently for presence of ALL MRD by 6-color FC. Results: The overall rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22% (4/18) of BM-positive cases. PB MRD sensitivity and specificity relative to BM MRD was 13% [95% confident interval (CI) 2%-42%] and 98% [88-100%] for B-ALL samples (n = 65) and 67% [13%-98%] and 75% [36%-95%] for T-ALL samples (n = 11), respectively. We identified 2 cases with evidence of leukemic cells in PB at the time of the extramedullary relapse that were interpreted as MRD-negative in BM. Conclusions: PB MRD demonstrates high specificity with relatively low sensitivity, especially in B-ALL when compared to T-ALL. The use of combined PB and BM samples in MRD assessment by current FC methods may have added clinical and diagnostic value in patients with high risk of extramedullary relapse, including PB MRD as a non-invasive method for monitoring of systemic relapse.
Comparison of myeloablative vs reduced intensity conditioning regimens in stem cell transplantations for acute myeloid leukemia.
Authors: Gurman Gunhan , Aydemir Guloksuz Gozde , Atilla Erden , Ataca Atilla Pinar , Civriz Bozdag Sinem , Kurt Yuksel Meltem , Toprak Selami Kocak , Topcuoglu Pervin , Ozcan Muhit , Arslan Onder , Demirer Taner , Akan Hamdi , Ilhan Osman , Beksac Meral
Published: September 2018

e18518

Background: The development of reduced intensity conditioning (RIC) regimens enabled allogeneic hematopoietic stem cell transplantations (allo-HSCT) also for patients who had contraindications and comorbidities for myeloablative conditioning (MAC) regimens. The aim of this study is to evaluate the effects of conditioning regimens on outcomes of alllo-HSCT for patients with acute myeloid leukemia. Methods: We retrospectively analysed 362 acute myeloid leukemia patients who underwent allo-HSCT between November 1989 to November 2016. We compared the outcomes of MAC vs RIC by Fisher’s test and chi-square test. Results: Engraftment was achieved in 87% of RIC and 95% of MAC recipients (p = 0.03).Incidences of acute and chronic graft vs host disease were not statistically different in groups (41% vs 47%, p = 0.7; 32% vs 43%, p = 0.2).Relapse rate was higher in RIC group (45% vs 25%, p = 0.02).Both 1-year overall survival (OS) and 1-year relapse free survival (RFS) rate were lower in the patients treated with RIC (71% vs 35%; 55% vs 16%).The higher OS was related with patients who were transplanted in remission, received grafts from related donors as well as having acute and chronic graft vs host disease. Conclusions: In the treatment of young patients who do not have comorbidities for intense conditioning regimens, show good performance status and are high risk; the initial use of standard myeloablative conditioning regimens is feasible. However, the lower number of RIC transplants and the variations between groups in terms of patient and donor characteristics might effect the results of this study. [Table: see text]
A validated symptomatic BKV risk assessment score in patient post allogeneic stem cell transplant.
Authors: Abudayyeh Ala , Lin Heather Y. , Abdelrahim Maen , Rondon Gabriela , Andersson Borje , Martinez Charles , Tarrand Jeffery , Chemaly Roy , Kontoyiannis Dimitrios P , Marin David , Olson Amanda Leigh , Champlin Richard E. , Shpall Elizabeth J. , Rezvani Katayoun
Published: September 2018

e18536

Background: BKV, Polyomavirus hominis 1, is a member of the family Polyomaviridae, is a non-enveloped virion; in the 1980s, it emerged as an important pathogen in SCT recipients. In the absence of sufficient T-cell immunity, BKV reactivation can progress, leading to prolonged hospital stays and increased mortality secondary to late hemorrhagic cystitis, ureteral stenosis, and nephropathy. In our recently completed retrospective study of 2477 SCT patients, 38.1% had developed renal impairment, and BKV viruria was present in 25%. In addition, BKV was found to be an independent predictor of chronic kidney disease and shorter survival. Using the large cohort (2477) patients studied earlier (2004-2012) we have derived a grading system to identify patients with risk of symptomatic BKV. We hypothesize that the current grading system will identify the patients at risk of symptomatic BKV at day 30 post allogeneic stem cell transplant. Methods: We performed a retrospective chart review of all patients who underwent allogeneic SCT from 2012-2016. The data was extracted from the secured database at MD Anderson cancer Center. Using the three variables that were significant predictor for symptomatic BKV derived from our initial study (conditioning regimen, HLA donor status, & underlying cancer diagnosis) we performed the analysis. Predicted cumulative incidence rate of BK infection at 30 days after transplant in 1308 patients were calculated in the presence of death as a competing risk using the “BASELINE” statement in PHREG procedure in SAS. Patients were classified into low, moderate and high risk according to the distribution of the predicted cumulative incidence of BK infection 30 days after transplant. Results: We have shown that the grading system derived from allogeneic SCT population predicted accurately the high, moderate & low risk population for developing symptomatic BKV. Conclusions: We have created and validated a grading system for symptomatic BKV in a large cohort of (1308 patients) to predict risk at day 30 post allogeneic SCT. Using this grading system we would hope to identify high risk patients for BKV and intervene early with novel therapies prior to complications associated.