The trends in the hemophilia treatment market are gaining momentum with increasing incidences of hemophilia A and B and staggering need for their treatments, including gene, anti-tissue factor pathway inhibitor, and factor replacement therapies. Before First-line non-targeted therapy options were available to individuals who received CGP and TGPT and no actionable gene variants were identified and to all in the no tumor profiling strategy. The use of comprehensive genomic profiling (CGP) in oncology has broad potential as a universal companion diagnostic for targeted therapies which may significantly improve health outcomes while using healthcare resources more efficiently. Lack of CGP Testing May Result in Missed Therapy Options in NSCLC. Healthcare costs in patients with advanced non-small cell lung cancer and disease progression during targeted therapy: a real-world observational study, Lung cancer costs by treatment strategy and phase of care among patients enrolled in Medicare, A Transparent and Consistent Approach to Assess US Outpatient Drug Costs for Use in Cost-Effectiveness Analyses, Determining the Cost of Pharmaceuticals for a Cost-Effectiveness Analysis, Surveillance, Epidemiology and End Results Program, Adjusting Health Expenditures for Inflation: A Review of Measures for Health Services Research in the United States, Updating cost-effectiveness--the curious resilience of the $50,000-per-QALY threshold. Therefore, it is essential to correctly identify the tumour entities/clinical settings where PCM can lead to clinically meaningful improvements in outcome. Digitizing lab results across all care settings and unlocking the potential of lab values can help health plans reach the Triple Aim of improving the patient experience, improving the health of populations, and reducing the per-member cost of health care. Mark G. Kris, MD: Im not sure theres any consensus definition for the terms personalized or precision medicine. Accessibility Compared to no tumor genomic profiling, tumor genomic profiling directing selection of first-line anticancer targeted therapies for patients with metastatic lung adenocarcinoma is not cost-effective. Specifically, our scenario analyses highlight important policy implications for prices of targeted therapies for patients with advanced NSCLC. Genomic data were used to support a site-specific WebThe 2024 predictions include 15 approved genomic biomarkers that may be targetable with particular therapies across all cancer types, more than 1.5 times the number approved by 2022 (see figure 2). Trdan et al (5) reported one of the largest series to date, including 2,579 patients with advanced cancers in the ProfiLER trial. e15162 Background: Next generation sequencing (NGS) can be used to detect tumor-specific genomic alterations, with the aim to identify actionable genomic alteration and provide additional treatment options for patients with advanced cancer. Cancer-directed therapy costs reflect regimens recommended in clinical guidelines and are summarized in Supplemental Table 4. No tumor profiling was the least costly strategy ($122,613/person) and resulted in the lowest number of QALYs (0.53/person), TGPT was more costly ($184,063/person) with higher number of QALYs (0.72/person), while CGP was the costliest strategy ($188,425/person) and with the highest number of QALYs (0.74/person) (Table 3). (50, 51). Before and transmitted securely. Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches. Health Care Cost. Methods: A provisional clinical opinion from the American Society of Clinical Oncology (ASCO) recommends that patients with advanced cancer with specific genomic alterations undergo genomic sequencing. 2022 Jun 18;14(12):3011. doi: 10.3390/cancers14123011. Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, Normanno N, Scarpa A, Robson M, Meric-Bernstam F, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. The special enrollment period for Affordable Care Act (ACA) coverage has opened to low-income Americans; the FDA approves the first drug for a rare genetic epilepsy disorder; the National Institutes of Health to launch biomarker testing program for pediatric tumors. (46) Targeted therapies are considered specialty drugs covered under Medicare Part D. Prices for these drugs are not publicly available, so the VA drug pricing was used. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. TGPT, an older tumor profiling approach, assesses the most commonly altered genomic regions of select cancer-associated genes typically ALK, BRAF, EGFR, ROS1 in NSCLC. Cost-effectiveness of multiplexed predictive biomarker screening in non-small-cell lung cancer, Cost Effectiveness of Multigene Panel Sequencing for Patients With Advanced Non-Small-Cell Lung Cancer. See this image and copyright information in PMC. Everyonenot only oncologists and oncology organizations but also payers, including Medicare and private insurers in the United Stateshave all realized that its better for the patient and more cost-effective to do your broad testing up front. For third-line therapy, 100% of patients remaining alive chose no anti-cancer therapy (Table 1). Among this cohort, 40 were selected based on an initial diagnosis of cancer of unknown primary. Next-generation sequencing is DNA sequencing on a massive scale, which enables multiple tests to be performed on limited amounts of tissue. Insurance. A closed cohort of 10,000 Medicare beneficiaries with metastatic lung adenocarcinoma considering frontline cancer-directed therapy was simulated and assigned to each of the three tumor profiling strategies. Using this approach, it is possible to map an individuals unique genomic profile, spanning several hundred different types of mutations. WebGreater insight into the molecular pathophysiology of cancer has prompted the adoption of molecular classification schemes that integrate genomic information with clinical Typically, we exclude patients with EGFR mutation: the other nonsmoker-related oncogenes from initial treatment with immunotherapy. Despite technological advancements, there are still many factors that can cause specimens for comprehensive genomic profiling (CGP) testing to become compromised, potentially leading to inaccurate prognostic results, according to a recent webinar. For example, lung cancer was once thought of as a single disease, but we now know it can be categorised into at least 12 distinct subtypes based on the molecular alterations (mutations) that drive its growth. In general, most people arent familiar with genomic profiling. We have to think about when wed say personalized medicine and precision medicine. A review of how comprehensive genomic profiling can better inform treatment planning and alleviate health care economic burden. Massard C, Michiels S, Fert C, Deley MC, Lacroix L, Hollebecque A, Verlingue L, Ileana E, Rosellini S, Ammari S, et al. sharing sensitive information, make sure youre on a federal Base-case scenario outcomes for each tumor profiling strategy included drug discontinuations, AEs, life years, death after each therapy line, QALYs, and cost. WebCosts (2019 US$) and quality-adjusted life-years (QALYs) were discounted at 3% per year. The ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (22) classifies genomic alterations based on the quality of existing evidence supporting their clinical actionability. The median (range) age at diagnosis was 70 (42-85) and 23 (57%) were female. Lee H, Park JH, Han J, Shim YM, Kim J, Choi YS, Kim HK, Cho JH, Choi YL, Kim WS. A research team at Taipei Veterans General Hospital (VGH-TPE), led by Chi-Cheng Huang, MD, PhD, has shown that comprehensive genomic profiling (CGP) can yield valuable information to help treat triple-negative breast cancer patients. Results: Base-case results and corresponding 95% credible intervals from the PSA indicated the cost/QALY gained was $309,399 ($280,371-$343,161) for TGPT and $324,707 ($296,086-$359,778) for MGPS compared to no tumor profiling. Cost-Effectiveness in Health and Medicine, 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, Pricing in the Market for Anticancer Drugs. Notes: Interventions were rank-ordered by total cost and sequentially compared. Federal government websites often end in .gov or .mil. In the example of nonsmall cell lung cancer, which is a poster child, several studies have shown that its more cost-effective to test for all the genes up front simultaneously with next-generation sequencing than it is using sequentially or exclusion testing where, you exclude certain abnormalities before you go to next-generation sequencing. Comprehensive genomic profiling (CGP) allows for the detection of driver alterations at high resolution, but the limited number of approved targeted therapies and their high costs have contributed to its limited clinical utilization. WebComprehensive genomic profiling for non-small-cell lung cancer: health and budget impact. (57) As more actionable gene variants are added to panel testing, targeted therapy will be indicated for more patients with advanced NSCLC. Mount Sinai Researchers Discuss Findings on Risk of Pathogenic, Loss-of-Function Clinical Variants. Rather, it has become the first thing you do before you initiate any systemic therapy in a patient with advanced cancer. The growing field of precision oncology, where systemic treatments are targeted to patients with specific genetic tumor profiles, has evolved dramatically since FDA approval of the first epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced NSCLC in 2003. See Supplemental Figure 6 for all threshold analyses and alternate scenario results. WebIntroduction. The $150,000 per QALY gained WTP threshold is indicated by the dotted line on the graphs. Threshold analyses and clinically relevant alternate scenarios varied select parameters identified in the one-way sensitivity analysis using published data or hypothetical ranges to further investigate the impact on the ICER. Mount Sinai Researchers Explain Implications of Genetic Testing for Providers. Assuming similar drug pricing moving forward, this may lead to higher ICERs when compared to tumor profiling strategies that do not detect these newer actionable gene variants, driven by the cost of placing more patients on targeted drugs for longer time periods. However, cost-effectiveness analyses of PCM are faced with several challenges and, thus, its cost-effectiveness remains unclear. Before Lets begin. Comprehensive genomic profiling identifies DNA mutations within a tumor to determine how it behaves and grows. Base-case values were derived from these studies and a 20% range was applied to the base-case value to derive the minimum and maximum range values for the sensitivity analyses. Maybe that becomes personalized in terms of how you distinguish it vs is it distinguished within thoracic oncology and within oncology in general? Where we would have once called this field science fiction, its impact is a reality today. Genomic data were used to support a site-specific Bethesda, MD 20894, Web Policies Unauthorized use of these marks is strictly prohibited. Before WebComprehensive genomic profiling (CGP) also known as biomarker testing or tumor profiling is a method of cancer sequencing using a single test to access hundreds of cancer relevant genes and detect genomic mutations known to drive cancer growth. The decision-making process for that patient will turn on its heel if 1 of the actionable oncogenes is found. 2016 Apr;10(2):113-29. doi: 10.1177/1753465815617871. No tumor profiling was the least costly/person ($122,613 vs $184,063 for TGPT and $188,425 for CGP), and yielded the least QALYs/person (0.53 vs 0.73 for TGPT and 0.74 for CGP). High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: Results of the MOSCATO 01 trial. EP: 1. Romanus D, Cardarella S, Cutler D, et al. Lakdawalla DN, Doshi JA, Garrison LP Jr., et al. Over 90 minutes today, were going to have conversations thats going to help you determine where we are with regard to that inflection point. Our study has several limitations to highlight. 8600 Rockville Pike Comparisons reflect the lifetime time horizon of 10,000 hypothetical patients with metastatic lung adenocarcinoma. the contents by NLM or the National Institutes of Health. (47) To convert VA prices to Medicare prices, 121% of drug prices reported in the FSS was used per VA recommendations. (37, 38) HSUVs are multiplied by the time spent in the health state and reported as QALYs over a specific time horizon. WTP thresholds ($0-$700,000) across which each intervention was most likely to convey the greatest QALYs at an acceptable incremental cost were summarized in Figure 2. Then nonsmall cell became histology-based adenocarcinoma squamous cell carcinoma, and then we started to add targets. This would be somewhat of a level set, but some of it will be philosophical in terms of how we interpret it and the role genomic profiling within the broader field of precision medicine. 1Department of Hematology, Oncology, Clinical Immunology and Rheumatology, Saarland University Medical Center, D-66421 Homburg, Germany, 2Ulm Comprehensive Cancer Center, Ulm University Hospital, D-89081 Ulm, Germany, 3Department of Internal Medicine III, Ulm University Hospital, D-89081 Ulm, Germany. Limits to personalized cancer medicine. Certain costs, such as data storage or the need for additional tests (germline or family members), are difficult to depict when accompanied by findings of unclear significance. The https:// ensures that you are connecting to the Cost-effectiveness of KRAS, EGFR and ALK testing for decision making in advanced nonsmall cell lung carcinoma: the French IFCT-PREDICT.amm study. Avalere Analyst on How Payers Are Handling Cell and Gene Therapy Cost Concerns. Genomic and transcriptomic profiling expands precision cancer medicine: The WINTHER trial. Suh JH, Johnson A, Albacker L, Wang K, Chmielecki J, Frampton G, Gay L, Elvin JA, Vergilio JA, Ali S, Miller VA, Stephens PJ, Ross JS. official website and that any information you provide is encrypted Next-Generation Sequencing Finds Different Molecular Profiles of Pediatric, Adult Sarcomas. Dr Voora reported receiving grants from National Institutes of Health during the conduct of the study. Mock A, Heilig CE, Kreutzfeldt S, Huebschmann D, Heining C, Schrck E, Brors B, Stenzinger A, Jger D, Schlenk R, Glimm H, Frhling S, Horak P; DKTK MASTER Network. Ron Do, PhD, associate professor, Charles Bronfman Institute for Personalized Medicine at Mount Sinai, and Iain Forrest, MD-PhD candidate in Dr Dos lab, explain their study's implications for providers and how age plays a role in genetic variant penetrance. Results: No tumor Ive had many examples in my clinic. Published studies using Medicare data linked with the Surveillance, Epidemiology, and End Results (SEER) program, the authoritative source of cancer incidence and mortality information in the U.S., was used for the cost of best supportive care and death. Unable to load your collection due to an error, Unable to load your delegates due to an error. Today nonsmall cell lung cancer could be 30 different diseases with targeted therapies that can have some intervention, either therapies approved or in the pipeline. Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: A prospective analysis. 2013 Jul;17(31):1-278. doi: 10.3310/hta17310. Use of commercial genomic testing has the potential to improve patient outcomes. Marino P, Pampallona S, Preatoni A, et al. In clinical practice, the presence of clinical frameworks, such as the Recommendations for the Use of NGS for Patients with Metastatic Cancers from the ESMO Precision Medicine Working Group, and the ESMO Scale for Clinical Actionability of Molecular Targets, are essential in appropriately identifying situations where PCM is clinically meaningful, thereby improving its cost-effectiveness. This ability to Im going to go to Mark on this, whos an expert in lung cancerwe started with lung cancer. National Library of Medicine Loubiere S, Drezet A, Beau-Faller M, et al. Robert NJ, Nwokeji ED, Espirito JL, et al. Deviations from these assumptions may affect the number of patients receiving targeted therapies. Therefore, the benefits of subsequent lines of therapy are likely smaller, which may inflate our QALY estimates and thus reduce our ICER values. To address these knowledge gaps and compare the health and cost outcomes associated with common tumor profiling approaches, we conducted a cost-effectiveness analysis to compare CGP, TGPT, and no tumor profiling with the objective of determining the lifetime cost-effectiveness for Medicare beneficiaries with metastatic lung adenocarcinoma from the Centers for Medicare and Medicaid Services (CMS) perspective. The remaining inputs (e.g., genetic alteration prevalence, tumor profiling cost, PFS, life expectancy) together explained 6% of the ICER variation. Cancer Stat Facts: Lung and Bronchus Cancer. When disease progression or therapy discontinuation occurred on a therapy, subsequent therapy lines were initiated. The increased costs of comprehensive molecular tumour profiling for each individual patient and the cost of targeted therapy itself, pose the question of the cost-effectiveness of this paradigm (3). The AJMC Comprehensive Genomic Profiling compendium is a comprehensive resource for clinical news and expert insights for the next-generation sequencing approach to assess genes for the purpose of therapy guidance. The SHIVA trial (4) randomized patients to receive either molecularly guided therapy or the physician's choice. Normanno N, De Luca A, Abate RE, Morabito A, Milella M, Tabb F, Curigliano G, Masini C, Marchetti P, Pruneri G, Guarneri V, Frassineti GL, Fasola G, Adamo V, Daniele B, Berardi R, Feroce F, Maiello E, Pinto C. Eur J Cancer. HHS Vulnerability Disclosure, Help One important challenge that has been highlighted is to provide meaningful measures of outcome in small-n basket/umbrella trials. After CGP was Cost-Effectiveness of Tumor Genomic Profiling to Guide First-Line Targeted Therapy Selection in Patients With Metastatic Lung Adenocarcinoma. Curr Oncol. The Effect of Advances in Lung-Cancer Treatment on Population Mortality, Real-time PCR and targeted next-generation sequencing in the detection of low level EGFR mutations: Instructive case analyses, Existing and emerging technologies for tumor genomic profiling, Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification, Next-generation sequencing for cancer diagnostics: a practical perspective. Point estimates for each input parameter were used in the base-case scenario and unless specified, represented the midpoint value if a range was reported in the literature (Table 1). Our findings not only provide evidence of incremental gains in QALYs, on average, with tumor profiling, but also motivate a discussion regarding value and cost in oncologic care. Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Endpoints like the progression-free survival (PFS)2/PFS1 ratio may assist in overcoming this issue. Assessing Cost Savings, Waste Reduction From Pharmacogenomics and Precision Medicine. Comprehensive genomic profiling (CGP) detects several classes of genomic alterations across numerous genes simultaneously and can match more Velcheti V, Patwardhan PD, Liu FX, et al. The likelihood of harboring an actionable gene variant associated with a first-line targeted therapy was based on actionable gene variant prevalence data. Bruce Feinberg, DO: Hello. From the Centers for Medicare and Medicaid perspective, the lifetime cost per quality-adjusted life years (QALY) gained is $310,735 (TGPT vs no tumor profiling) and $445,545 (CGP vs TGPT) for patients with metastatic lung adenocarcinoma. A meta-analysis of trials conducted between 2005 and 2016 by Schwarze et al (14) showed that cost estimates ranged from $555 to $5,169 for whole exome sequencing (WES) and from $1,906 to $24,810 for whole genome sequencing (WGS). Our panel of experts will discuss comprehensive genomic profiling and how its As a service to our customers we are providing this early version of the manuscript. 2022 Jan-Dec;25(1):817-825. doi: 10.1080/13696998.2022.2080463. Comprehensive molecular profiling of Taiwanese breast cancers revealed potential therapeutic targets: prevalence of actionable mutations among 380 targeted sequencing analyses. When the Human Genome Project was initiated in the 1990s, it became apparent that Sanger sequencing would have been too slow and expensive to sequence the whole human genome. Adjusting for health benefits and inflation, cancer-directed drug prices have increased by almost 12% per year since the 1990s. We retrospectively compared data of 946 women with ovarian cancer (11.4% were referred to CGP, and We focus on 3 kinds of biomarkers in this context. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. However, the financial burden of PCM is currently primarily driven by the cost of targeted treatment itself, rather than by diagnostic measures. Precision cancer medicine (PCM) is an emerging paradigm in oncology, which includes tumour comprehensive genomic profiling (CGP) to enable molecularly guided therapy. The established measure of efficacy in the era of evidence-based medicine, the placebo-controlled phase III randomised trial, is nearly impossible to apply in the context of PCM. Innovative endpoints, like the PFS2/PFS1 ratio, used in the WINTHER and MOSCATO trials show promise in addressing this issue (7). Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: Analysis from the ProfiLER trial. For second-line therapies, 29% remaining alive received no anti-cancer therapy, 69% received chemotherapy, and 2% received immunotherapy. Harnessing the promise of molecular information, developing new strategies with partners to evolve the practice of personalised cancer care, and facilitating comprehensive genomic profiling are significantly advancing cancer care for patients, and we are proud to be leading the way in this area. Bruce Feinberg, DO: Kenna, do you agree or disagree? In 33% of the patients (63/193), the PFS was at least 30% longer compared with previous-line therapy (PFS2/PFS1 ratio >1.3). Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. While this obviously requires a great degree of experience and depends on the individual situation, the actionability of any individual alteration itself can be quantified to a certain extent. The MOSCATO trial (6) was a single-arm, prospective trial of high-throughput genomics-based targeted therapy in patients with advanced cancers, reporting an ORR of 11%. Kim J, Jeong K, Jun H, Kim K, Bae JM, Song MG, Yi H, Park S, Woo GU, Lee DW, Kim TY, Lee KH, Im SA. (56) Finally, our study is limited by the rapid evolution of NSCLC management and subsequent updates to clinical guidelines. official website and that any information you provide is encrypted Further advancements in clinical trial design, evaluation of clinical outcomes and, most importantly, the costs associated with PCM are required for adequate assessment of its cost-effectiveness. No other disclosures were reported. Sanger sequencing became the most widely used sequencing method for the next two decades and is still in use today for small-scale projects. No tumor profiling detected 0% of the cohort with actionable gene variants as expected, compared to 22.0% for TGPT and 29.6% for CGP (Table 2). The site is secure. official website and that any information you provide is encrypted 2020 Nov;31(11):1491-1505. doi: 10.1016/j.annonc.2020.07.014. (53) Professional society guidelines recommend broad molecular profiling(12, 54), however the optimal tumor profiling strategy remains uncertain, and tumor profiling uptake is not uniform. Tumor genomic profiling directing selection of first-line cancer-directed targeted therapies does not generate sufficient gains in QALYs to offset the high price of these therapies. I was always jealous of investigators working in the breast cancer field because they had some extremely potent targets for therapy. WebThe total medical costs in the CGP group were 9.143 billion JPY (67.726 million USD) (total cost of genomic test: 1.155 billion JPY [8.556 million USD]; cost of treatments: 7.988 This has been shown to be the same in bloodthat its more cost-effective in blood to do next-generation sequencing. The https:// ensures that you are connecting to the Bethesda, MD 20894, Web Policies Published by Elsevier Inc. All rights reserved. Chakravarty D, Gao J, Phillips SM, et al. While smaller sequencing panels are being applied broadly, controversy exists around the For example, accidental identification of a germline BRCA1/2 mutation could lead to risk-reducing mastectomy, initially causing an increase in healthcare costs. Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: Incremental yield of actionable alterations and cost-effectiveness analysis. The site is secure. Kalemkerian GP, Narula N, Kennedy EB, et al. Bruce, you already outlined the evolution that we had going to the histologic definition and later the molecular definition. The $150,000 per QALY gained WTP threshold is indicated by the dotted line on the graphs.
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