Clinical and Economic Value of a Biosimilar Portfolio to Stakeholders: An Integrative Literature Review.

Purpose: While the value of individual biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings between biosimilars and originators. Stakeholders may consider the value of a manufacturer's biosimilar portfolio, especially when negotiating portfolio-based contracts or other rebate programs. However, little is known about what other types of value, in addition to financial benefits, decision-makers perceive regarding a manufacturer with a biosimilar portfolio compared to those without one. The objective of this integrative literature review was to describe a conceptual framework consisting of themes that may help define the value of a biosimilar portfolio. Methods: An integrative literature review was conducted using Excerpta Medica Database (Embase) and Medical Literature Analysis and Retrieval System Online (MEDLINE). Grey literature searches of search engines, journals not indexed in Embase or MEDLINE, healthcare payers, health technology assessment bodies, value frameworks, and non-pharmaceutical industry analogs were also conducted. Eligible studies reported on the value of a biosimilar portfolio in decision-making by stakeholders. Apart from the literature, insights were gained from clinical experience and observation. Results: No studies investigating biosimilar portfolio value were identified; however, several themes were identified that may help define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; and transaction costs. Several non-pharmaceutical industry analogs were identified: Product line length and single-supplier versus multiple-supplier procurement. Several themes were identified through other sources: Science credibility and research. Based on these themes, we developed a conceptual framework for biosimilar portfolio value. Conclusion: To our knowledge, this is the first study to systematically assess and create a framework for biosimilar portfolio value. The conceptual framework described here could be tested to quantify the clinical and economic value associated with a biosimilar portfolio.

Though the value of single biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings incurred between biosimilars and originators.We identified seven themes that may help to define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; transaction costs; science credibility; and research.These themes may be integrated into a conceptual framework that may form a basis to help quantify the clinical and economic benefit of a biosimilar portfolio to stakeholders.

Cost-Effectiveness of Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Older Patients With High-Risk Myelodysplastic Syndrome: Analysis of BMT CTN 1102.

PURPOSE: BMT CTN 1102 was a phase III trial comparing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT) to standard of care for persons with intermediate- or high-risk myelodysplastic syndrome (MDS). We report results of a cost-effectiveness analysis conducted alongside the clinical trial. METHODS: Three hundred eighty-four patients received HCT (n = 260) or standard of care (n = 124) according to availability of a human leukocyte antigen-matched donor. Cost-effectiveness was calculated from US commercial and Medicare perspectives over a 20-year time horizon. Health care utilization and costs were estimated using propensity score-matched cohorts of HCT recipients in the OptumLabs Data Warehouse (age 50-64 years) and Medicare (age 65 years and older). EuroQol 5 Dimension (EQ-5D) surveys of trial participants were used to derive health state utilities. RESULTS: Extrapolated 20-year overall survival for those age 50-64 years was 29% for HCT (n = 105) versus 13% for usual care (n = 44) and 31% for HCT (n = 155) versus 12% for non-HCT (n = 80) for those age 65 years and older. HCT was more effective (+2.36 quality-adjusted life-years [QALYs] for age 50-64 years and +2.92 QALYs for age 65 years and older) and more costly (+$452,242 in US dollars (USD) for age 50-64 years and +$233,214 USD for age 65 years and older) than usual care, with incremental cost-effectiveness ratios of $191,487 (USD)/QALY and $79,834 (USD)/QALY, respectively. For persons age 50-64 years, there was a 29% chance that HCT was cost-effective using a willingness-to-pay (WTP) threshold of $150K (USD)/QALY and 51% at a $200K (USD)/QALY. For persons age 65 years and older, the probability was 100% at a WTP >$150K (USD)/QALY. CONCLUSION: Among patients age 65 years and older with high-risk MDS, RIC HCT is a high-value strategy. For those age 50-64 years, HCT is a lower-value strategy but has similar cost-effectiveness to other therapies commonly used in oncology.

The Impact of Biosimilar Use on Total Cost of Care and Provider Financial Performance in the Medicare Oncology Care Model: A Population-Based Simulation Study.

INTRODUCTION: Payment for oncology care is increasingly moving from fee-for-service to value-based payment (VBP). VBPs are agreements in which providers are held accountable for total cost of care (TCOC) through risk-sharing arrangements with payers that tie reimbursement levels to TCOC benchmarks. Oncology biosimilars may play an important role in managing financial risk in the VBPs like Medicare's Oncology Care Model (OCM), but there has been limited research in this area. The objective of this study is to estimate the impact of biosimilar adoption on TCOC and oncology provider financial performance under the terms of the Medicare OCM. METHODS: We conducted a population-based simulation study using the Medicare Limited Data Set (LDS) and the methodology of Medicare's OCM. The primary outcome was the simulated average change in TCOC per 6-month episode of care attributable to use of biosimilars as an alternative to reference products. The study population consisted of episodes of care in 2020 and using the reference product or corresponding biosimilar for bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, or pegfilgrastim. TCOC was calculated for each episode of care with use of reference products only and compared with TCOC with corresponding biosimilars. The simulation calculated TCOC outcomes in cohorts of 100 episodes sampled from the Medicare LDS study population using a Monte Carlo simulation with 10,000 iterations. RESULTS: Among the total of 8281 6-month oncology care episodes identified in the study period (initiating January 2020 to July 2020) in Medicare claims, 1586 (19.2%) episodes met OCM and study criteria and were included. Applying the simulation methods to these observed episodes, biosimilar substitution reduced mean TCOC per episode by $1193 (95% CI $583-1840). The cost reduction from biosimilars represented 2.4% of the average TCOC benchmark and led to a 15% reduction in the risk of providers needing to pay recoupments to Medicare for exceeding TCOC benchmarks. CONCLUSIONS: On the basis of our simulation study using observed Medicare claims and OCM criteria, we found that biosimilar substitution for reference products can significantly lower episode TCOC and improve provider financial performance under the terms of the largest value-based payment model implemented to date.

Cost-Effectiveness of Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Bone Marrow Transplantation: Evidence from BMT CTN 1101.

BMT CTN 1101 was a Phase III randomized controlled trial comparing reduced-intensity conditioning followed by double unrelated umbilical cord blood transplantation (UCBT) versus HLA-haploidentical related donor bone marrow transplantation (haplo-BMT) for patients with high-risk hematologic malignancies. Here we report the results of a parallel cost-effectiveness analysis of these 2 hematopoietic stem cell transplantation (HCT) techniques. In this study, 368 patients were randomized to unrelated UCBT (n = 186) or haplo-BMT (n = 182). We estimated healthcare utilization and costs using propensity score-matched haplo-BMT recipients from the OptumLabs Data Warehouse for trial participants age <65 years and Medicare claims for participants age ≥65 years. Weibull models were used to estimate 20-year survival. EQ-5D surveys by trial participants were used to estimate quality-adjusted life-years (QALYs). At a 5-year follow-up, survival was 42% for haplo-BMT recipients versus 36% for UCBT recipients (P = .06). Over a 20-year time horizon, haplo-BMT is expected to be more effective (+.63 QALY) and more costly (+$118,953) for persons age <65 years. For those age ≥65 years, haplo-BMT is expected to be more effective and less costly. In one-way uncertainty analyses, for persons age <65, the cost per QALY result was most sensitive to life-years and health state utilities, whereas for those age ≥65, life- years were more influential than costs and health state utilities. Compared to UCBT, haplo-BMT was moderately more cost-effective for patients age <65 years and less costly and more effective for persons age ≥65 years. Haplo-BMT is a fair value choice for commercially insured patients with high-risk leukemia and lymphoma who require HCT. For Medicare enrollees, haplo-BMT is a preferred choice when considering costs and outcomes.

Translating an Economic Analysis into a Tool for Public Health Resource Allocation in Cancer Survivorship.

Background. The complexity of decision science models may prevent their use to assist in decision making. User-centered design (UCD) principles provide an opportunity to engage end users in model development and refinement, potentially reducing complexity and increasing model utilization in a practical setting. We report our experiences with UCD to develop a modeling tool for cancer control planners evaluating cancer survivorship interventions. Design. Using UCD principles (described in the article), we developed a dynamic cohort model of cancer survivorship for individuals with female breast, colorectal, lung, and prostate cancer over 10 y. Parameters were obtained from the National Program of Cancer Registries and peer-reviewed literature, with model outcomes captured in quality-adjusted life-years and net monetary benefit. Prototyping and iteration were conducted with structured focus groups involving state cancer control planners and staff from the Centers for Disease Control and Prevention and the American Public Health Association. Results. Initial feedback highlighted model complexity and unclear purpose as barriers to end user uptake. Revisions addressed complexity by simplifying model input requirements, providing clear examples of input types, and reducing complex language. Wording was added to the results page to explain the interpretation of results. After these updates, feedback demonstrated that end users more clearly understood how to use and apply the model for cancer survivorship resource allocation tasks. Conclusions. A UCD approach identified challenges faced by end users in integrating a decision aid into their workflow. This approach created collaboration between modelers and end users, tailoring revisions to meet the needs of the users. Future models developed for individuals without a decision science background could leverage UCD to ensure the model meets the needs of the intended audience. Highlights: Model complexity and unclear purpose are 2 barriers that prevent lay users from integrating decision science tools into their workflow.Modelers could integrate the user-centered design framework when developing a model for lay users to reduce complexity and ensure the model meets the needs of the users.

Assessment of the Cost-Effectiveness of HER2-Targeted Treatment Pathways in the Neoadjuvant Treatment of High-Risk HER2-Positive Early-Stage Breast Cancer.

INTRODUCTION: This study aims to assess differences in costs and benefits of treatment strategies for high-risk human epidermal growth factor receptor 2 positive (HER2+) early-stage breast cancer (ESBC). METHODS: We used a hybrid decision-tree/Markov model to simulate costs and outcomes across six health states: Invasive disease-free, non-metastatic recurrence, remission, first-line and second-line metastatic cancer, and death. We considered several strategies, defined by four attributes: (1) Neoadjuvant targeted therapy (infused pertuzumab and trastuzumab (PH) versus subcutaneous fixed-dose combination (FDC) of pertuzumab and trastuzumab versus trastuzumab alone (H)); (2) adjuvant targeted therapy if pathological complete response (pCR) is achieved (PH, FDC, or H); (3) adjuvant targeted therapy (T-DM1 or H) in the case of residual disease (RD); and (4) use of branded or biosimilar H. Transition probabilities were derived from relevant clinical trials. We included drug costs and costs associated with adverse events and administration. Health state utilities were obtained from clinical trials and the literature. RESULTS: Strategies not containing T-DM1 were dominated (worse outcomes and greater costs) by strategies containing T-DM1. Among strategies with pertuzumab continuation in the case of pCR and T-DM1 in the case of RD, use of FDC was dominant (equivalent outcomes and lower costs), relative to strategies using infused therapies, regardless of biosimilar versus branded trastuzumab. Adjuvant continuation of FDC was also cost-effective (better outcomes at reasonable cost increases) relative to strategies which discontinued pertuzumab following pCR. CONCLUSION: Dual targeted therapy via FDC (with transition to T-DM1 in the case of RD) is a cost-effective treatment strategy in high-risk HER2+ ESBC.

Potential Cost-Effectiveness of Risk-Based Pancreatic Cancer Screening in Patients With New-Onset Diabetes.

BACKGROUND: There are no established methods for pancreatic cancer (PAC) screening, but the NCI and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in patients with new-onset diabetes (NOD), a group with elevated PAC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) risk model validation study, we assessed the potential value of CT screening for PAC in those determined to be at elevated risk, as is being done in a planned PanCAN Early Detection Initiative trial. METHODS: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of PAC screening in patients aged ≥50 years with NOD using CT imaging versus no screening. PAC prevalence, sensitivity, and specificity were derived from the END-PAC validation study. PAC stage distribution in the no-screening strategy and PAC survival were derived from the SEER program. Background mortality for patients with diabetes, screening and cancer care expenditure, and health state utilities were derived from the literature. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2020 US dollars, and we took a limited US healthcare perspective. RESULTS: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $293 in additional expenditures for a cost per QALY gained of $65,076. In probabilistic analyses, screening resulted in a cost per QALY gained of <$50,000 and <$100,000 in 34% and 99% of simulations, respectively. In the threshold analysis, >25% of screen-detected PAC cases needed to be resectable for the cost per QALY gained with screening to be <$100,000. CONCLUSIONS: We found that risk-based PAC screening in patients with NOD is likely to be cost-effective in the United States if even a modest fraction (>25%) of screen-detected patients with PAC are resectable. Future studies should reassess the value of this intervention once clinical trial data become available.

A Budget Impact Analysis of Gene Therapy for Sickle Cell Disease: The Medicaid Perspective.

Importance: Hundreds of gene therapies are undergoing clinical testing and are likely to be priced more than $1 million per course of treatment. The association that high prices will have with insurance coverage of gene therapy remains unclear. Gene therapy for sickle cell disease has shown early success and would be one of the first gene therapies available for a relatively large population. Objectives: To estimate the budget impact and affordability of a gene therapy for severe sickle cell disease from the perspective of US Medicaid programs with the highest prevalence of sickle cell disease while exploring the impact of an annuity payment model. Design, Setting, and Participants: A budget impact analysis was performed from January 1 to May 31, 2020, for a sickle cell disease gene therapy from the perspective of 10 state Medicaid plans with a 5-year time horizon, using state-level disease prevalence data from 2012. Disease prevalence, Medicaid enrollment, and expenditures were derived from the available literature. The eligible population was based on modified clinical trial inclusion criteria including individuals aged 13 to 45 years with severe disease. Exposures: The gene therapy was assumed to be administered to 7% of the eligible population annually and was curative (no subsequent disease-related expenditures). The gene therapy price was $1.85 million in the base case, and baseline disease-related expenditures were $42 200 per year. Main Outcomes and Measures: The main outcomes were total budget impact and budget impact per member per month in years 1 through 5. One-way sensitivity analysis was used to evaluate uncertainty of market diffusion, size of eligible population, price of therapy, and cost of routine care. Results: An estimated 5464 Medicaid enrollees would be eligible for the gene therapy nationally, with 2315 individuals in the 10 Medicaid programs of interest (16 per 100 000 enrollees). The model projected a mean 1-year budget impact of $29.96 million per state Medicaid program in the sample ($1.91 per member per month). A 5-year annuity payment reduced the short-term budget impact. Conclusions and Relevance: This study suggests that a gene therapy for severe sickle cell disease is likely to produce a considerable budget impact for many Medicaid plans while potentially offering substantial benefit to patients. Payers may need to take steps to ensure affordability and access. Gene therapy for sickle cell disease is likely to provide an early demonstration of the unique financial challenges associated with this emerging drug class.

A comparison of mixture cure fraction models to traditional parametric survival models in estimation of the cost-effectiveness of nivolumab for relapsed small cell lung cancer.

BACKGROUND: In August 2018, the US FDA granted accelerated approval for nivolumab in small cell lung cancer (SCLC) that has progressed after platinum-based chemotherapy and at least one other line of therapy. The objective of this study was to evaluate the cost-effectiveness of nivolumab vs. usual care as third-line (3 L) therapy for patients with recurrent SCLC (rSCLC) from the health payer perspective. Given the potential for a meaningful fraction of treated patients to achieve long-term response to nivolumab, we also assessed the impact of using mixture cure modeling (MCM) vs. parametric survival modeling on survival estimates and cost-effectiveness from the US Medicare payer perspective. METHODS: We created a partitioned survival decision model to assess the cost-effectiveness of 3 L nivolumab vs. usual care in rSCLC, based on observed US treatment patterns. Using this approach, we assessed the impact of extrapolating long-term survival from the CheckMate 032 trial, using both MCM and standard parametric curve fits. Nivolumab survival, resource use, and Grade 3/4 adverse event rates were derived from CheckMate 032. Usual care survival, resource use, and costs were derived from an analysis of patients receiving 3 L treatment for rSCLC in the SEER-Medicare registry. We applied 2020 Wholesale Acquisition Cost for drugs and 2020 CMS reimbursement for procedures. Utilities were derived from the literature. We estimated life years (LY), quality-adjusted life years (QALYs), and costs over a lifetime horizon. RESULTS: MCM and parametric survival model extrapolations resulted in 0.43 versus 0.38 more LYs, 0.34 versus 0.30 more QALYs, and $69,308 versus $61,336 more expenditure for nivolumab vs. usual care, respectively. The costs per QALY gained using mixture cure versus parametric survival modeling were $204,386 and $207,431, respectively. CONCLUSIONS: Mixture cure modeling was equivalent compared to parametric modeling in estimating the cost-effectiveness of nivolumab-based therapy due to the small fraction of patients achieving a long-term response with nivolumab (12.9%).

Value and affordability of CAR T-cell therapy in the United States.

In the United States the increasing number of Food and Drug Administration (FDA)-approved, innovative, and potentially effective commercial cancer therapies pose a significant financial burden on public and private payers. Chimeric antigen receptor (CAR) T cells are prototypical of this challenge. In 2017 and 2018, tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Kite) were approved by the FDA for use after showing groundbreaking results in relapsed/refractory B-cell malignancies. In 2020 and 2021, four further submissions to the FDA are expected for CAR T-cell therapies for indolent and aggressive B-cell malignancies and plasma cell myeloma. Yet, with marketed prices of over $350,000 per infusion for the two FDA-approved therapies and similar price tags expected for the coming products, serious concerns are raised over value and affordability. In this review we summarize recent, peer-reviewed cost-effectiveness studies of tisagenlecleucel and axicabtagene ciloleucel in the United States; discuss key issues concerning the health plan budget impact of CAR T-cell therapy; and review policy, payment and scientific approaches that may improve the value and affordability of CAR T-cell therapy.

The Women's Health Initiative Estrogen-alone Trial had differential disease and medical expenditure consequences across age groups.

OBJECTIVES: The Women's Health Initiative (WHI) randomized trial identified age differences in the benefit-risk profile of estrogen-alone (ET) use. The impact of WHI trial on disease-associated medical expenditures attributable to subsequent decreased ET utilization has, however, not been measured. Therefore, the objective of this analysis was to quantify the age-specific disease-associated medical expenditures attributable to reduced ET utilization after the WHI Hormone Therapy (HT) trials. METHODS: Population-level disease counts and associated expenditures between 2003 and 2015 were compared between an observed ET-user population versus a hypothetical ET-user population assuming absence of the WHI HT trials, constructed by extrapolating ET utilization rates from 1996 to 2002 assuming pre-WHI HT rates would have continued without publication of the WHI HT trial data (2002-2004). Analyses were stratified by age (50-59, 60-69, and 70-79 years). Input data were extracted from Medical Expenditure Panel Survey and the literature. The primary outcomes were: ET utilization, chronic diseases (breast cancer, stroke, coronary heart disease, colorectal cancer, pulmonary embolism, and hip fracture) and disease-associated direct medical expenditures. RESULTS: Over 13 years, the decline in ET utilization was associated with $4.1 billion expenditure for excess chronic diseases (37,549 excess events) among women in their 50s, compared to savings of $1.5 billion and $4.4 billion for diseases averted by lower ET utilization among women in their 60s (13,495 fewer events) and 70s (40,792 fewer events), respectively. CONCLUSION: The decline in ET utilization had differential disease and expenditure consequences by age groups in the United States. These results are limited by the lack of inclusion of vasomotor symptom benefit and costs of alternative medications for these symptoms in the analysis.

Safety and Costs of Endobronchial Ultrasound-Guided Nodal Aspiration and Mediastinoscopy.

BACKGROUND: There remains debate over the best invasive diagnostic modality for mediastinal nodal evaluation. Prior studies have limited generalizability and insufficient power to detect differences in rare adverse events. We compared the risks and costs of endobronchial ultrasound (EBUS)-guided nodal aspiration and mediastinoscopy performed for any indication in a large national cohort. METHODS: We conducted a retrospective study (2007-2015) with MarketScan, a claims database of individuals with employer-provided insurance in the United States. Patients who underwent multimodality mediastinal evaluation (n = 1,396) or same-day pulmonary resection (n = 2,130) were excluded. Regression models were used to evaluate associations between diagnostic modalities and risks and costs while adjusting for patient characteristics, year, concomitant bronchoscopic procedures, and lung cancer diagnosis. RESULTS: Among 30,570 patients, 49% underwent EBUS. Severe adverse events-pneumothorax, hemothorax, airway/vascular injuries, or death-were rare and invariant between EBUS and mediastinoscopy (0.3% vs 0.4%; P = .189). The rate of vocal cord paralysis was lower for EBUS (1.4% vs 2.2%; P < .001). EBUS was associated with a lower adjusted risk of severe adverse events (OR, 0.42; 95% CI, 0.32-0.55) and vocal cord paralysis (OR, 0.57; 95% CI, 0.54-0.60). The mean cost of EBUS was $2,211 less than mediastinoscopy ($6,816 vs $9,023; P < .001). After adjustment this difference decreased to $1,650 (95% CI, $1,525-$1,776). CONCLUSIONS: When performed as isolated procedures, EBUS is associated with lower risks and costs compared with mediastinoscopy. Future studies comparing the effectiveness of EBUS vs mediastinoscopy in the community at large will help determine which procedure is superior or if trade-offs exist.

Intensity modulated radiation therapy following lumpectomy in early-stage breast cancer: Patterns of use and cost consequences among Medicare beneficiaries.

PURPOSE: In 2013, the American Society for Radiation Oncology (ASTRO) issued a Choosing Wisely recommendation against the routine use of intensity modulated radiotherapy (IMRT) for whole breast irradiation. We evaluated IMRT use and subsequent impact on Medicare expenditure in the period immediately preceding this recommendation to provide a baseline measure of IMRT use and associated cost consequences. METHODS AND MATERIALS: SEER records for women ≥66 years with first primary diagnosis of Stage I/II breast cancer (2008-2011) were linked with Medicare claims (2007-2012). Eligibility criteria included lumpectomy within 6 months of diagnosis and radiotherapy within 6 months of lumpectomy. We evaluated IMRT versus conventional radiotherapy (cRT) use overall and by SEER registry (12 sites). We used generalized estimating equations logit models to explore adjusted odds ratios (OR) for associations between clinical, sociodemographic, and health services characteristics and IMRT use. Mean costs were calculated from Medicare allowable costs in the year after diagnosis. RESULTS: Among 13,037 women, mean age was 74.4, 50.5% had left-sided breast cancer, and 19.8% received IMRT. IMRT use varied from 0% to 52% across SEER registries. In multivariable analysis, left-sided breast cancer (OR 1.75), living in a big metropolitan area (OR 2.39), living in a census tract with ≤$90,000 median income (OR 1.75), neutral or favorable local coverage determination (OR 3.86, 1.72, respectively), and free-standing treatment facility (OR 3.49) were associated with receipt of IMRT (p<0.001). Mean expenditure in the year after diagnosis was $8,499 greater (p<0.001) among women receiving IMRT versus cRT. CONCLUSION: We found highly variable use of IMRT and higher expenditure in the year after diagnosis among women treated with IMRT (vs. cRT) with early-stage breast cancer and Medicare insurance. Our findings suggest a considerable opportunity to reduce treatment variation and cost of care while improving alignment between practice and clinical guidelines.

Cost-Effectiveness Analysis of Adjuvant Neratinib Following Trastuzumab in Early-Stage HER2-Positive Breast Cancer.

BACKGROUND: Disease-free survival (DFS) in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer is significantly greater with the addition of neratinib after adjuvant trastuzumab versus no additional therapy. However, it remains uncertain whether these survival gains represent good value for the money, given the substantial cost of neratinib. OBJECTIVE: To evaluate clinical and economic implications of adding neratinib after adjuvant trastuzumab based on results from the phase III ExteNET trial. METHODS: A 3-state Markov model was developed to estimate the cost-effectiveness of neratinib for women with early-stage (I-III) HER2-positive breast cancer. Five-year recurrence rates were derived from the ExteNET trial. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical expenditures. The analysis was performed from a payer perspective over a lifetime horizon. One-way sensitivity and probabilistic analyses were conducted to evaluate uncertainty. RESULTS: Total cost of neratinib following adjuvant trastuzumab was $317,619 versus $152,812 for adjuvant trastuzumab alone. A gain of 0.4 QALYs (15.7 vs. 15.3) and 0.1 years of projected life expectancy (18.3 vs. 18.2) favored neratinib after trastuzumab versus trastuzumab alone. The neratinib cost per QALY gained was $416,106. At standard willingness-to-pay thresholds of $50,000, $100,000, and $200,000 per QALY gained, neratinib has a probability of 2.8%, 16.7%, and 33.9% of cost-effectiveness, respectively. The cost per QALY gained in a scenario analysis only including patients with hormone-receptor positive disease was $275,311. CONCLUSIONS: Based on 5-year data from ExteNET, neratinib following adjuvant trastuzumab is not projected to be cost-effective, even among those patients shown to derive the greatest clinical benefit. Future analyses should reassess the cost-effectiveness associated with neratinib treatment as trial data mature. DISCLOSURES: No outside funding supported this study. Roth reports consulting fees from Genentech. Steuten reports grants from AstraZeneca, EMD Serono, and Genomic Health, along with personal fees from Agendia, unrelated to this study. The other authors have no conflicts of interest in connection with this study.

Clinical and Budget Impact of Increasing Colorectal Cancer Screening by Blood- and Stool-Based Testing.

BACKGROUND: Screening for colorectal cancer (CRC) is effective at reducing mortality, but nearly 35% of eligible patients do not get screened. New noninvasive screening methods may help increase CRC screening participation. Current CRC screening methods include blood-based screening with methylated Septin 9 (SEPT9) DNA (Epi proColon), stool-based screening with fecal immunochemical testing (FIT), and the multianalyte fecal test combining FIT and stool DNA (Cologuard). OBJECTIVES: To estimate the cost and clinical implications to health plans, including the clinical and fiscal implications of the use of blood-based screening with SEPT9 DNA, FIT, and FIT/stool DNA, for patients who are unwilling or unable to undergo other recommended screening methods, and to quantify the clinical and fiscal impacts on health plans of expanding CRC screening participation from today's level of 65% up to 80%. METHODS: We designed a simulation model to estimate the 3-year clinical and economic impacts for noninvasive screening scenarios and for no screening in the screening-nonadherent population. Clinical inputs were derived from SEPT9, FIT, and FIT/stool DNA validation studies in the peer-reviewed literature, the US census, and other sources in the peer-reviewed literature. We modeled a population of 1 million covered lives (aged 0-64 years) in a hypothetical health plan to estimate CRC, advanced adenoma, and nonadvanced adenoma diagnoses for different screening scenarios. We also modeled the expenditures related to screening, diagnostic follow-up, and treatment costs for CRC for a 15% increase (34,800 members) to 80% screening over the course of 3 years. RESULTS: In the health plan population, 232,000 members aged 50 to 64 years were eligible for screening, of whom 81,200 (35%) were unscreened. The number of cases of CRC that were detected was similar for each screening scenario, including 221 for SEPT9, 216 for FIT, and 193 for FIT/stool DNA versus 49 for no screening. The 3-year per-member per-month (PMPM) cost impact for screening versus no screening and the evaluation of positive tests for the scenarios was $0.67 for SEPT9, $0.33 for FIT, and $0.69 for FIT/stool DNA. Including the treatment costs for CRC, the PMPM costs increased to $1.08, $0.71, and $0.98, respectively. CONCLUSIONS: Our simulation model suggests that similar clinical detection rates are achievable with the 3 noninvasive blood- and stool-based screening methods. These results support a role for blood- and stool-based screening to increase participation in CRC screening.

Cost-effectiveness of axicabtagene ciloleucel for adult patients with relapsed or refractory large B-cell lymphoma in the United States.

PURPOSE: Axicabtagene ciloleucel (axi-cel) was recently approved for treatment of relapsed or refractory (R/R) large B-cell lymphoma (LBCL) following two or more prior therapies. As the first CAR T-cell therapy available for adults in the US, there are important questions about clinical and economic value. The objective of this study was to assess the cost-effectiveness of axi-cel compared to salvage chemotherapy using a decision model and a US payer perspective. MATERIALS AND METHODS: A decision model was developed to estimate life years (LYs), quality-adjusted life years (QALYs), and lifetime cost for adult patients with R/R LBCL treated with axi-cel vs salvage chemotherapy (R-DHAP). Patient-level analyses of the ZUMA-1 and SCHOLAR-1 studies were used to inform the model and to estimate the proportion achieving long-term survival. Drug and procedure costs were derived from US average sales prices and Medicare reimbursement schedules. Future healthcare costs in long-term remission was derived from per capita Medicare spending. Utility values were derived from patient-level data from ZUMA-1 and external literature. One-way and probabilistic sensitivity analyses evaluated uncertainty. Outcomes were calculated over a lifetime horizon and were discounted at 3% per year. RESULTS: In the base case, LYs, QALYs, and lifetime costs were 9.5, 7.7, and $552,921 for axi-cel vs 2.6, 1.1, and $172,737 for salvage chemotherapy, respectively. The axi-cel cost per QALY gained was $58,146. Cost-effectiveness was most sensitive to the fraction achieving long-term remission, discount rate, and axi-cel price. The likelihood that axi-cel is cost-effective was 95% at a willingness to pay of $100,000 per QALY. CONCLUSION: Axi-cel is a potentially cost-effective alternative to salvage chemotherapy for adults with R/R LBCL. Long-term follow-up is necessary to reduce uncertainties about health outcomes.

Survival Gains from First-Line Systemic Therapy in Metastatic Non-Small Cell Lung Cancer in the U.S., 1990-2015: Progress and Opportunities.

BACKGROUND: Approximately 190,000 Americans are diagnosed with non-small cell lung cancer (NSCLC) annually, and about half have metastatic (Stage IV) disease. These patients have historically had poor survival prognosis, but several new therapies introduced since 2000 provide options for improved outcomes. The objectives of this study were to quantify survival gains from 1990, when best supportive care (BSC) only was standard, to 2015 and to estimate the impact of expanded use of systemic therapies in clinically appropriate patients. MATERIALS AND METHODS: We developed a simulation model to estimate survival gains for patients with metastatic NSCLC from 1990-2015. Survival estimates were derived from major clinical trials and extrapolated to a lifetime horizon. Proportions of patients receiving available therapies were derived from the Surveillance, Epidemiology, and End Results database and a commercial treatment registry. We also estimated gains in overall survival (OS) in scenarios in which systemic therapy use increased by 10% and 30% relative to current use. RESULTS: From 1990-2015, one-year survival proportion increased by 14.1% and mean per-patient survival improved by 4.2 months (32,700 population life years). Increasing treated patients by 10% or 30% increased OS by 5.1 months (39,700 population life years) and 6.9 months (53,800 population life years), respectively. CONCLUSION: Although survival remains poor in metastatic NSCLC relative to other common cancers, meaningful progress in per-patient and population-level outcomes has been realized over the past 25 years. These advances can be improved even further by increasing use of systemic therapies in the substantial proportion of patients who are suitable for treatment yet who currently receive BSC only. The Oncologist 2017;22:304-310 IMPLICATIONS FOR PRACTICE: Approximately 93,500 Americans are diagnosed with metastatic non-small cell lung cancer (NSCLC) annually. Historically, these patients have had poor survival prognosis, but newer therapies provide options for improved outcomes. This simulation modeling study quantified metastatic NSCLC survival gains from 1990-2015. Over this period, the one-year survival proportion and mean per-patient survival increased by 14.1% and 4.2 months, respectively. Though metastatic NSCLC survival remains poor, the past 25 years have brought meaningful gains. Additional gains could be realized by increasing systemic therapy use in the substantial proportion of patients who are suitable for treatment, yet currently receive only supportive care.

A qualitative study exploring why individuals opt out of lung cancer screening.

Background: Lung cancer screening with annual low-dose computed tomography is relatively new for long-term smokers in the USA supported by a US Preventive Services Task Force Grade B recommendation. As screening programs are more widely implemented nationally and providers engage patients about lung cancer screening, it is critical to understand behaviour among high-risk smokers who opt out to improve shared decision-making processes for lung cancer screening. Objective: The purpose of this study was to explore the reasons for screening-eligible patients' decisions to opt out of screening after receiving a provider recommendation. Methods: Semi-structured qualitative telephone interviews were performed with 18 participants who met lung cancer screening criteria for age, smoking and pack-year history in Washington State from November 2015 to January 2016. Two researchers with cancer screening and qualitative methodology expertise conducted data analysis using thematic content analytic procedures from audio-recorded interviews. Results: Five primary themes emerged for reasons of opting out of lung cancer screening: (i) Knowledge Avoidance; (ii) Perceived Low Value; (iii) False-Positive Worry; (iv) Practical Barriers; and (v) Patient Misunderstanding. Conclusion: The participants in our study provided insight into why some patients make the decision to opt out of low-dose computed tomography screening, which provides knowledge that can inform intervention development to enhance shared decision-making processes between long-term smokers and their providers and decrease decisional conflict about screening.

Economic Analysis of Prostate-Specific Antigen Screening and Selective Treatment Strategies.

IMPORTANCE: Prostate-specific antigen (PSA) screening for prostate cancer is controversial. Experts have suggested more personalized or more conservative strategies to improve benefit-risk tradeoffs, but the value of these strategies-particularly when combined with increased conservative management for low-risk cases-is uncertain. OBJECTIVES: To evaluate the potential cost-effectiveness of plausible PSA screening strategies and to assess the value added by increased use of conservative management among low-risk, screen-detected cases. DESIGN, SETTING, AND PARTICIPANTS: A microsimulation model of prostate cancer incidence and mortality was created. A simulated contemporary cohort of US men beginning at 40 years of age underwent 18 strategies for PSA screening. Treatment strategies included (1) contemporary treatment practices based on age and cancer stage and grade observed in the Surveillance, Epidemiology, and End Results program in 2010 or (2) selective treatment practices whereby cases with a Gleason score lower than 7 and clinical T2a stage cancer or lower are treated only after clinical progression, and all other cases undergo contemporary treatment practices. National and trial data on PSA growth, screening and biopsy patterns, incidence of prostate cancer, treatment distributions, treatment efficacy, mortality, health-related quality of life, and direct medical expenditure were analyzed. Data were collected from March 18, 2009, to August 15, 2014, and analyzed from November 20, 2012, to December 11, 2015. INTERVENTIONS: Eighteen screening strategies that vary by start and stop age, screening interval, and criteria for biopsy referral and contemporary or selective treatment practices. MAIN OUTCOMES AND MEASURES: Life-years (LYs), quality-adjusted life-years (QALYs), direct medical expenditure, and cost per LY and QALY gained. RESULTS: All 18 screening strategies were associated with increased LYs (range, 0.03-0.06) and costs ($263-$1371) compared with no screening, with the cost ranging from $7335 to $21 649 per LY. With contemporary treatment, only strategies with biopsy referral for PSA levels higher than 10.0 ng/mL or age-dependent thresholds were associated with increased QALYs (0.002-0.004), and only quadrennial screening of patients aged 55 to 69 years was potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio, $92 446). With selective treatment, all strategies were associated with increased QALYs (0.002-0.004), and several strategies were potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio, $70 831-$136 332). CONCLUSIONS AND RELEVANCE: For PSA screening to be cost-effective, it needs to be used conservatively and ideally in combination with a conservative management approach for low-risk disease.