Complexity of Delivering Precision Medicine: Opportunities and Challenges

2018 ◽  
pp. 998-1007 ◽  
Author(s):  
Andrew A. Davis ◽  
Amy E. McKee ◽  
Warren A. Kibbe ◽  
Victoria M. Villaflor
Keyword(s):  
Clinical Trials ◽  
Precision Medicine ◽  
Data Sharing ◽  
Response To Treatment ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Data Repositories ◽  
Molecular Features ◽  
Effective Manner ◽  
Tumor Boards

Precision medicine has emerged as a tool to match patients with the appropriate treatment based on the precise molecular features of an individual patient’s tumor. Although examples of targeted therapies exist resulting in dramatic improvements in patient outcomes, comprehensive genomic profiling of tumors has also demonstrated the incredible complexity of molecular alterations in tissue and blood. These sequencing methods provide opportunities to study the landscape of tumors at baseline and serially in response to treatment. These tools also serve as important biomarkers to detect resistance to treatment and determine higher likelihood of responding to particular treatments, such as immune checkpoint blockade. Federally funded and publicly available data repositories have emerged as mechanisms for data sharing. In addition, novel clinical trials are emerging to develop new ways of incorporating molecular matched therapy into clinical trials. Various challenges to delivery of precision oncology include understanding the complexity of advanced tumors based on evolving “omics” and treatment resistance. For physicians, determining when and how to incorporate genetic and molecular tools into clinic in a cost-effective manner is critical. Finally, we discuss the importance of well-designed prospective clinical trials, biomarkers such as liquid biopsies, the use of multidisciplinary tumor boards, and data sharing as evidence-based medicine tools to optimally study and deliver precision oncology to our patients.

Implementing Precision Medicine Programs and Clinical Trials in the Community-Based Oncology Practice: Barriers and Best Practices

2018 ◽  
pp. 188-196 ◽  
Author(s):  
Jennifer L. Ersek ◽  
Lora J. Black ◽  
Michael A. Thompson ◽  
Edward S. Kim
Keyword(s):  
Clinical Trials ◽  
Best Practices ◽  
Precision Medicine ◽  
Community Setting ◽  
Successful Implementation ◽  
Precision Oncology ◽  
Community Based ◽  
Molecular Tests ◽  
Core Components ◽  
Oncology Practice

There has been a rapid uptick in the pace of oncology precision medicine advancements over the past several decades as a result of increasingly sophisticated technology and the ability to study more patients through innovative trial designs. As more precision oncology approaches are developed, the need for precision medicine trials is increasing in the community setting, where most patients with cancer are treated. However, community-based practices, as well as some academic centers, may face unique barriers to implementing precision medicine programs and trials within their communities. Such challenges include understanding the tissue needs of molecular tests (e.g., tumor, blood), identifying which molecular tests are best used and when tissue should be tested, interpreting the test results and determining actionability, understanding the role of genetic counseling and/or follow-up testing, determining clinical trial eligibility, and assessing patient attitudes and financial concerns. The purpose of this article is to provide guidance to community-based oncology practices currently conducting clinical trials who want to expand their research program to include precision medicine trials. Here, we describe the core components of precision medicine programs and offer best practices for successful implementation of precision medicine trials in community-based practices.

scholarly journals Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 129 ◽  
Author(s):  
Richard D. Beger ◽  
Michael A Schmidt ◽  
Rima Kaddurah-Daouk
Keyword(s):  
Clinical Trials ◽  
Drug Treatment ◽  
Precision Medicine ◽  
Metabolic Profile ◽  
Biomarker Discovery ◽  
Response To Treatment ◽  
Individual Response ◽  
Patient Response ◽  
Drug Mechanism ◽  
The Individual

Pharmacometabolomics (PMx) studies use information contained in metabolic profiles (or metabolome) to inform about how a subject will respond to drug treatment. Genome, gut microbiome, sex, nutrition, age, stress, health status, and other factors can impact the metabolic profile of an individual. Some of these factors are known to influence the individual response to pharmaceutical compounds. An individual’s metabolic profile has been referred to as his or her “metabotype.” As such, metabolomic profiles obtained prior to, during, or after drug treatment could provide insights about drug mechanism of action and variation of response to treatment. Furthermore, there are several types of PMx studies that are used to discover and inform patterns associated with varied drug responses (i.e., responders vs. non-responders; slow or fast metabolizers). The PMx efforts could simultaneously provide information related to an individual’s pharmacokinetic response during clinical trials and be used to predict patient response to drugs making pharmacometabolomic clinical research valuable for precision medicine. PMx biomarkers can also be discovered and validated during FDA clinical trials. Using biomarkers during medical development is described in US Law under the 21st Century Cures Act. Information on how to submit biomarkers to the FDA and their context of use is defined herein.

scholarly journals Implementing Precision Medicine in Community-Based Oncology Programs: Three Models

2019 ◽  
Vol 15 (6) ◽  
pp. 325-329 ◽  
Author(s):  
Laura A. Levit ◽  
Edward S. Kim ◽  
Barbara L. McAneny ◽  
Lincoln D. Nadauld ◽  
Kathryn Levit ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Cancer Care ◽  
Large Scale ◽  
Administrative Support ◽  
Clinical Pathways ◽  
Clinical Decision ◽  
Successful Implementation ◽  
Precision Oncology ◽  
Community Based ◽  
Tumor Boards

The use of precision medicine and the number of genomic-based treatments and immunotherapies is increasing. Nevertheless, oncology providers face challenges to implementing precision medicine, including in community practices, where most patients receive treatment. On January 31, 2018, ASCO hosted Precision Medicine: Expanding Opportunities, the inaugural event in ASCO’s new State of Cancer Care in America (SOCCA) event series. This article draws from the inaugural SOCCA event and the experiences of the SOCCA event participants to summarize the opportunities and challenges of precision medicine, and to highlight three successful models of implementing precision oncology in large, multisite community practices or networks: (1) Intermountain Healthcare, (2) Levine Cancer Institute, Atrium Health, and (3) National Cancer Care Alliance. The experience of these practices suggests that practice innovations that offer clinical decision support through molecular tumor boards and clinical pathways, and administrative support for prior authorization and clinical trial matching are key to successful implementation of large-scale, community-based precision medicine programs.

scholarly journals Precision Medicine in Oncology Pharmacy Practice

2019 ◽  
Vol 48 (1) ◽  
pp. 90
Author(s):  
Claire Saadeh ◽  
David Bright ◽  
Danielle Rustem
Keyword(s):  
Drug Therapy ◽  
Supportive Care ◽  
Precision Medicine ◽  
Somatic Mutations ◽  
Treatment Options ◽  
Pharmacy Practice ◽  
Standard Of Care ◽  
Individual Variability ◽  
Precision Oncology ◽  
Tumor Boards

<p>The objective of this review is to provide an overview of the components, process and resources available to apply precision medicine strategies to drug therapy in cancer medicine, with an emphasis on oncology pharmacy practice. Precision medicine initiatives in oncology take into account individual variability in genes, environment and lifestyle factors. Genomic assays of patient tumors is now the standard of care in oncology and recommendations for targeted drug therapies are often formulated by interprofessional teams. Pharmacogenomics (PGx) is a component of precision medicine based on polymorphisms that impact medication selection and/or dosing. Several oncolytic agents used in the treatment of cancer and supportive care have pharmacogenomic-based dosing recommendations to minimize potential toxicities. Several resources are reviewed here to guide treatment options in oncology as they relate to somatic mutations and PGx. Examples include: OncoKB is a precision oncology knowledge base that offers evidence-based information for somatic mutations. The Clinical Pharmacogenetics Implementation Consortium provides PGx-based guidelines for several oncolytic therapies used to treat cancer and for supportive care. Pharmacists can be integral members of the interprofessional team in many practicesettings in precision medicine. Involvement can include membership in molecular tumor boards, PGx dosing services and provide patient education.</p><p><strong>Conclusion. </strong>Precision medicine is a rapidly evolving field in oncology that requires an interprofessional approach of drug therapy experts.</p>

scholarly journals Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board

2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mark E. Burkard ◽  
Dustin A. Deming ◽  
Benjamin M. Parsons ◽  
Paraic A. Kenny ◽  
Marissa R. Schuh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Precision Medicine ◽  
Clinical Utility ◽  
Journal Club ◽  
Academic Community ◽  
Tumor Board ◽  
Observational Research ◽  
Evidence Based ◽  
Precision Oncology ◽  
Molecular Tumor Board

Purpose Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region. Materials and Methods We developed a statewide molecular tumor board that integrates academic and community oncology practices. The Precision Medicine Molecular Tumor Board (PMMTB) has three components: a biweekly Web-based teleconference tumor board meeting provided as a free clinical service, an observational research registry, and a monthly journal club to establish and revise evidence-based guidelines for off-label therapies. The PMMTB allows for flexible and rapid implementation of treatment, uniformity in practice, and the ability to track outcomes. Results We describe the implementation of the PMMTB and its first year of activity. Seventy-seven patient cases were presented, 48 were enrolled in a registry, and 38 had recommendations and clinical follow-up. The 38 subjects had diverse solid tumors (lung, 45%; GI, 21%; breast, 13%; other, 21%). Of these subjects, targeted therapy was recommended for 32 (84%). Clinical trials were identified for 24 subjects (63%), and nontrial targeted medicines for 16 (42%). Nine subjects (28%) received recommended therapy with a response rate of 17% (one of six) and a clinical benefit rate (partial response + stable disease) of 38% (three of eight). Although clinical trials often were identified, patients rarely enrolled. Conclusion The PMMTB provides a model for a regional molecular tumor board with clinical utility. This work highlights the need for outcome registries and improved access to clinical trials to pragmatically implement precision oncology.

scholarly journals Precision oncology: mind the disruption

2016 ◽  
Vol 38 (1) ◽  
pp. 14-18
Author(s):  
Richie Soong ◽  
Nicholas Syn ◽  
Katherine Wang ◽  
Mohamed Feroz Bin Mohammed Omar
Keyword(s):  
Precision Medicine ◽  
Health Management ◽  
Healthcare Management ◽  
Precision Oncology ◽  
Clinical Practices ◽  
Molecular Features ◽  
New Information ◽  
Cancer Types ◽  
New Treatments ◽  
Key Events

Over the last two decades, treatment outcomes have improved markedly for a number of cancer types, including breast cancer, lung cancer and melanoma. Some of these improvements can be attributed to the steady development of new treatments. However, what has been very different in this period is the introduction of a different approach to healthcare management. Precision medicine is a strategy of customizing health management to individual predisposition and condition subtype, instead of the conventional approach of applying a standardized management. In oncology, a move towards precision medicine has been motivated by an accumulating number of paradigms that have demonstrated its significant health and financial value. However, shifting to this type of medicine entails many disruptions to current research and clinical practices, including the introduction of new disciplines and structures, new levels of multidisciplinary co-operation, new approaches to health regulation and economics and the generation of new information on inter-population clinical and molecular features. In this article, we look back at key events in precision oncology to relate the motivation behind the shift and understand the upcoming issues in realizing the immense potential of precision medicine.

scholarly journals The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4324
Author(s):  
Karin P. S. Langenberg ◽  
Eleonora J. Looze ◽  
Jan J. Molenaar
Keyword(s):  
Precision Medicine ◽  
Pediatric Patients ◽  
Molecular Profiling ◽  
Immune Monitoring ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Childhood Malignancies ◽  
Combination Strategies ◽  
Number Of Patients ◽  
Definition Of

Over the last years, various precision medicine programs have been developed for pediatric patients with high-risk, relapsed, or refractory malignancies, selecting patients for targeted treatment through comprehensive molecular profiling. In this review, we describe characteristics of these initiatives, demonstrating the feasibility and potential of molecular-driven precision medicine. Actionable events are identified in a significant subset of patients, although comparing results is complicated due to the lack of a standardized definition of actionable alterations and the different molecular profiling strategies used. The first biomarker-driven trials for childhood cancer have been initiated, but until now the effect of precision medicine on clinical outcome has only been reported for a small number of patients, demonstrating clinical benefit in some. Future perspectives include the incorporation of novel approaches such as liquid biopsies and immune monitoring as well as innovative collaborative trial design including combination strategies, and the development of agents specifically targeting aberrations in childhood malignancies.

An Overview of Promising Biomarkers in Cancer Screening and Detection

2020 ◽  
Vol 20 (11) ◽  
pp. 831-852
Author(s):  
Saba Hasan
Keyword(s):  
Clinical Trials ◽  
Clinical Care ◽  
Clinical Information ◽  
Cost Effective ◽  
Response To Treatment ◽  
Effective Manner ◽  
Oncology Clinical Trials ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Applications of biomarkers have been proved in oncology screening, diagnosis, predicting response to treatment as well as monitoring the progress of the disease. Considering the crucial role played by them during different disease stages, it is extremely important to evaluate, validate, and assess them to incorporate them into routine clinical care. In this review, the role of few most promising and successfully used biomarkers in cancer detection, i.e. PD-L1, E-Cadherin, TP53, Exosomes, cfDNA, EGFR, mTOR with regard to their structure, mode of action, and reports signifying their pathological significance, are addressed. Also, an overview of some successfully used biomarkers for cancer medicine has been presented. The study also summarizes biomarker-driven personalized cancer therapy i.e., approved targets and indications, as per the US FDA. The review also highlights the increasingly prominent role of biomarkers in drug development at all stages, with particular reference to clinical trials. The increasing utility of biomarkers in clinical trials is clearly evident from the trend shown, wherein ~55 percent of all oncology clinical trials in 2019 were seen to involve biomarkers, as opposed to ~ 15 percent in 2001, which clearly proves the essence and applicability of biomarkers for synergizing clinical information with tumor progression. Still, there are significant challenges in the implementation of these possibilities with strong evidence in cost-- effective manner.

Avenues to Precision Oncology

2020 ◽  
pp. 36-45
Author(s):  
Alexander Meisel
Keyword(s):  
Precision Medicine ◽  
Trial Design ◽  
Ad Hoc ◽  
Molecular Targets ◽  
Clinical Trial Design ◽  
Predictive Biomarkers ◽  
Precision Oncology ◽  
Companion Diagnostics ◽  
Bona Fide ◽  
The One

Until recently, the clinical management of cancer heavily relied on anatomical and histopathological criteria, with ad hoc guidelines directing the therapeutic choices in specific indications. In the last years, the development and therapeutic implementation of novel anticancer therapies significantly improved the clinical outcome of cancer patients. Nonetheless, such cutting-edge approaches revealed the limitation of the one-size-fits-all paradigm. The newly discovered molecular targets can be exploited either as bona fide targets for subsequent drug development, or as tools to precision medicine, in the form of prognostic and/or predictive biomarkers. This article provides an overview of some of the most recent advances in precision medicine in oncology, with a focus on novel tissue-agnostic anticancer therapies. The definition and implementation of biomarkers and companion diagnostics in clinical trials and clinical practice are also discussed, as well as the changing landscape in clinical trial design.

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