Biomarker Tests for Molecularly Targeted Therapies Key to Unlocking Precision Medicine (2016) / Chapter Skim
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5 Processes to Improve Patient Care
5 Processes to Improve Patient Care
Pages 183-226
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. This chapter discusses processes to improve patient care in the context of biomarker tests and molecularly targeted therapies, including equity in access to testing and relevant expertise, ensuring patient safety and adequate test performance, and the implications for generating evidencebased clinical practice guidelines.
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a Personal communication, Simon Mallal, Vanderbilt University Medical Center, May 6, 2015. CURRENT CHALLENGES IN TEST RESULT INTERPRETATION In the current era of precision medicine, physicians seeking to incorporate emerging tools into the management of their patients will increasingly use advanced biomarker tests to guide treatment (Evans and Khoury, 2013)
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. An early example of the paradigm of using a single biomarker test to select patients likely to benefit from a molecularly targeted therapy is the use of trastuzumab in breast cancer.
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It is hoped that these analyses will help explore biological mechanisms of disease and lead to new predictive markers and improved drug and diagnostic development. The Metastatic Breast Cancer Project is a related research initiative that seeks to use social media to recruit patients with metastatic breast cancer to further the understanding of patient genomics and response to therapy.
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. HER2 testing has improved as a result of these guidelines and other efforts to standardize testing performance and interpretation criteria, although questions remain regarding whether some patients whose breast cancer is negative for HER2 overexpression might benefit from treatment with trastuzumab (Ithimakin et al., 2013)
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. The role for biomarker tests to guide the use of radiation therapy in combination with molecularly targeted therapy is largely unclear; similar to the original trials of molecularly targeted therapies in unselect ed patient populations, initial trials assessing this interaction were disappointing ( Higgins et al., 2015; Morris and Harari, 2014)
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. Due to the evolving nature of the evidence for the clinical use of predictive biomarker tests, careful consideration of the use of molecularly targeted therapies in general clinical practice is necessary to avoid potentially exposing patients to unnecessary risk for uncertain benefit.
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Additionally, fair access requires that health care professionals possess the expertise to properly order tests and interpret the results to determine optimal therapy selection, in spite of the challenges posed by the rapid pace of clinical knowledge development outlined previously. Potential Obstacles to Public Access and Understanding Fair access to effective biomarker testing for molecularly targeted therapies may be jeopardized by a number of factors.
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. Research also suggests that minority patients are more likely to report an unmet need for discussion of genetic testing with their physician (e.g., for breast cancer risk and corresponding risk-reducing treatment)
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Government Accountability Office (GAO) testi fied that the companies offering direct-to-consumer genetic testing made disease predictions that were not supported by evidence (GAO, 2006)
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. Health insurance coverage was discussed as a primary method to ensure access to care in Delivering High-Quality Cancer Care, though the report acknowledged that access alone would not ensure quality, and recommended the development of innovative, community-focused programs aimed at identifying and reducing disparities (IOM, 2013)
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. Thus, the uninsured and underinsured remain a population that is vulnerable to lack of access to health care services in general and in particular to precision medicine and molecularly targeted therapies.
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For example, many cancer patients believe that having their tumor genome sequenced will result in the discovery of a mutation that will enable successful treatment of their cancer with a targeted therapy. However, recent studies have found that potentially actionable targets are identified in less than half of patients specimens sequenced (an exception is an abstract presented at ASCO's 2015 annual meeting, which reported identification of actionable targets in 77 percent of specimens)
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It is essential that during efforts to standardize the analytic and clinical validity and develop evidence of the clinical utility of biomarker tests for molecularly targeted therapies, resources be dedicated to a comprehensive investigation and assessment of disparities in access to both testing and expertise. These may be due to a variety of economic, ethnic, cultural, and geographic factors, and once identified, efforts should be focused on reducing such disparities.
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. However, assessments of competency related to biomarker tests and their use for directing targeted therapies are lacking outside of certain specialties (e.g., pathology)
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and related tools to enhance clinician decision making, but as precision medicine continues to expand into medical practice in general, the committee recommends that licensing and specialty boards should ensure that health care professionals have and maintain competencies needed for effective use of biomarker tests for molecularly targeted therapies (Recommendation 8c)
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Policy mechanisms to ensure that clinicians and patients have access to additional expertise, as needed, are necessary to limit the inappropriate use of biomarker tests for molecularly targeted therapies. Larger health care centers and academic medical centers are able to leverage multidisciplinary expertise to ensure evidence-based treatment in the care of patients with complex conditions.
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can be used to deliver clinical consultation with or without real-time clinician and patient interaction, for example, and electronic communication and mobile technologies facilitate remote monitoring and health education of patients and health care providers (ATA, 2015; CCHPCA, 2015)
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. To ensure judicious use of biomarker tests and molecularly targeted therapies, the committee recommends that the Secretary of HHS and CMS should conduct demonstration projects to design and assess the effectiveness of collaborative partnerships between community health care providers and larger health care centers and/or academic medical centers to be part of a rapid learning system (Recommendation 8b)
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, and can delay a patient's access to molecularly targeted therapies or hinder collaborative research that requires specimen collection across diverse clinical settings (Dolgin, 2016)
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. The complexity involved in consistently obtaining adequate specimens requires communication throughout the entire health care team, including clinicians, surgeons, radiologists, and laboratory professionals, as well as consideration of the unique clinical conditions of each patient (Yamaguchi et al., 2012)
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; cancer biomarker tests for molecularly targeted therapies, for example, may be performed on specimens with varying requirements13 (Dietel et al., 2015; IOM, 2015)
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.15 A role exists for professional societies to help ensure the integrity of biomarker testing for molecularly targeted therapies, through the development of specimen acquisition and testing guidelines for the most frequently ordered tests (Dietel et al., 2015; Schilsky, 2014)
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10) Molecularly targeted therapies represent promising treatment options for patients suffering from the conditions these drugs are approved to treat; however, the ability for biomarker test results to suggest the use of molecularly targeted therapies in other conditions (particularly in oncology)
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and increased pressure for more frequent guideline updates. The inclusion of a biomarker test and corresponding molecularly targeted therapy in a trustworthy CPG can lead to more effective use in clinical practice.
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. However, despite the need to incorporate higher quality evidence into guideline development related to biomarker testing for molecularly targeted therapies, progress has been slow.
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. Similarly, Abernethy and colleagues examined the difficulty associated with traditional systematic review in technology assessment for off-label use of targeted therapies in cancer.
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Non-Small Cell Lung Cancer ALK 1, 2A EGFR 1, 2A ROS1 2A KRAS 2A BRAF 2A ERBB2 (HER2) 2B MET 2A RET 2A Breast Cancer ESR1 2A PGR 2A ERBB2 (HER2)
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, and others) should expand interdisciplinary collaborations to develop integrated guidelines on the appropriate use of biomarker tests for molecularly targeted therapies (Recommendation 10)
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Genetic counselors have an important role to play as members of the care team, working to inform physicians about interpretation of test results and to explain biomarker test results to patients. Goal 8: Promote equity in access to biomarker tests for molecularly targeted therapies and the expertise for effective use of the results in clinical decision making.
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Goal 10: Improve the processes for developing and updating clini cal practice guidelines for the effective use of biomarker tests for molecularly targeted therapies. Recommendation 10: Guideline-developing organizations (e.g., the College of American Pathologists, Association for Molecular Pathology, American College of Medical Genetics and Genomics, American College of Cardiology, National Comprehensive Cancer Network, American Heart Association, American Society of Clini cal Oncology, American College of Physicians, and others)
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They should conform to standards articulated by authoritative groups, including the Institute of Medicine and Guidelines International Network. • Guideline developers should consider the evolving clinical utility evidence, relative to the standards discussed in Recommendation 1, and from the proposed rapid learning system for biomarker tests.
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2014. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: A multicentre, prospective trial (SAFIR01/UNICANCER)
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Breast Cancer Research and Treatment 149(2)
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2015. Pragmatic issues in biomarker evaluation for targeted therapies in cancer.
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Journal of Clinical Oncology 31(15)
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2011. Effects of tissue handling on RNA integrity and microar ray measurements from resected breast cancers.
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2015. Policy issues in the development and adoption of biomarkers for molecularly targeted cancer therapies: Workshop summary.
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2015. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA)
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2005a. Impact of direct-to-consumer advertising for hereditary breast cancer testing on genetic services at a managed care organization: A naturally-occurring experiment.
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Written input to the Committee on Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies, June 15, 2015, Washington, DC. Peterson, E
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2012. PET imaging of estrogen receptors as a diagnostic tool for breast cancer patients presenting with a clinical dilemma.
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Presentation to the Committee on Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Thera pies, April 1, 2015, Washington, DC. Wolff, A
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