Practical considerations for personalized medicine in thyroid cancer: Which therapies are suited to particular patient profiles?

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    Faculty & Disclosures
    Prof. Marcia S Brose

    Jefferson Torresdale Hospital, Philadelphia, USA

    Marcia S Brose, MD, PhD, is Sidney Kimmel Cancer Center’s regional chief of cancer services at Jefferson Torresdale Hospital and medical co-director of community clinical research. Prof. Brose is an internationally recognized expert in thyroid cancer, rare cancers and personalized therapy. read more

    Prof. Brose has served as principal investigator on pivotal, practice-changing trials in thyroid cancer and is active in translational and clinical research. She has been invited to lecture and teach physicians in the USA, Europe, Asia, and Central and South America on the emerging treatments for advanced thyroid cancers.

    Throughout her career, Prof. Brose has received numerous honours and recognitions, including the Leadership Development Program Award from the American Society of Clinical Oncology, Clinical Investigator Award from Damon Runyon-Siemens, and a V Scholar Award from the V Foundation. Most recently, she was recognized as a Fellow of the American Society of Clinical Oncology.

    Professor Marcia S Brose discloses: Advisory board or panel fees from Aadi Bioscience, Eisai and Eli Lilly (relationships terminated). Consultancy fees from Bayer Healthcare, Eisai (relationship terminated) and Exelixis (relationship terminated). Grants/research support from Eli Lilly and Kinnate Biopharma.
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    Practical considerations for personalized medicine in thyroid cancer: Which therapies are suited to particular patient profiles?

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    Marcia S Brose, MD, PhD, is Sidney Kimmel Cancer Center’s regional chief of cancer services at Jefferson Torresdale Hospital and medical co-director of community clinical research. Prof. Brose is an internationally recognized expert in thyroid cancer, rare cancers and personalized therapy. read more

    Prof. Brose has served as principal investigator on pivotal, practice-changing trials in thyroid cancer and is active in translational and clinical research. She has been invited to lecture and teach physicians in the USA, Europe, Asia, and Central and South America on the emerging treatments for advanced thyroid cancers.

    Throughout her career, Prof. Brose has received numerous honours and recognitions, including the Leadership Development Program Award from the American Society of Clinical Oncology, Clinical Investigator Award from Damon Runyon-Siemens, and a V Scholar Award from the V Foundation. Most recently, she was recognized as a Fellow of the American Society of Clinical Oncology.

    Professor Marcia S Brose discloses: Advisory board or panel fees from Aadi Bioscience, Eisai and Eli Lilly (relationships terminated).  Consultancy fees from Bayer Healthcare, Eisai (relationship terminated) and Exelixis (relationship terminated). Grants/research support from Eli Lilly and Kinnate Biopharma.

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    Marcia S Brose, MD, PhD, is Sidney Kimmel Cancer Center’s regional chief of cancer services at Jefferson Torresdale Hospital and medical co-director of community clinical research. Prof. Brose is an internationally recognized expert in thyroid cancer, rare cancers and personalized therapy. read more

    Prof. Brose has served as principal investigator on pivotal, practice-changing trials in thyroid cancer and is active in translational and clinical research. She has been invited to lecture and teach physicians in the USA, Europe, Asia, and Central and South America on the emerging treatments for advanced thyroid cancers.

    Throughout her career, Prof. Brose has received numerous honours and recognitions, including the Leadership Development Program Award from the American Society of Clinical Oncology, Clinical Investigator Award from Damon Runyon-Siemens, and a V Scholar Award from the V Foundation. Most recently, she was recognized as a Fellow of the American Society of Clinical Oncology.

    Professor Marcia S Brose discloses: Advisory board or panel fees from Aadi Bioscience, Eisai and Eli Lilly (relationships terminated).  Consultancy fees from Bayer Healthcare, Eisai (relationship terminated) and Exelixis (relationship terminated). Grants/research support from Eli Lilly and Kinnate Biopharma.

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    Learning Objectives

    After watching this activity, participants should be better able to:

    • Identify the different types of thyroid cancer and the recommended methods to test for specific biomarkers
    • Evaluate the rationale and latest clinical evidence for current and emerging targeted therapies for thyroid cancer
    • Outline the indications, precautions and special considerations related to targeted therapies for personalized thyroid cancer care
    Overview

    Internationally renowned medical oncologist Prof. Marcia S Brose explores the importance of molecular pathology and individual patient profiles in guiding personalized medicine in thyroid cancer to deliver optimal outcomes.

    This activity is jointly provided by USF Health and touchIME. read more

    Target Audience

    Validated thyroid cancer specialists, including, oncologists, thyroid cancer specialists, oncology surgeons, endocrinologists, radiologists, pathologists and specialist oncology nurses involved in the management of thyroid cancer.

    Disclosures

    USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

    Faculty

    Professor Marcia S Brose discloses: Advisory board or panel fees from Aadi Bioscience, Eisai and Eli Lilly (relationships terminated). Consultancy fees from Bayer Healthcare, Eisai (relationship terminated) and Exelixis (relationship terminated). Grants/research support from Eli Lilly and Kinnate Biopharma.

    Content reviewer

    Alicia Canalejo, APRN, has no financial interests/relationships or affiliations in relation to this activity.

    Touch Medical Contributor

    Anne Nunn has no financial interests/relationships or affiliations in relation to this activity.

    USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

    Requirements for Successful Completion

    In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

    If you have questions regarding credit please contact cpdsupport@usf.edu.

    Accreditations

    Physicians

    This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

    USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

    Advanced Practice Providers

    Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

    The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

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    USF Health is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation.

    A maximum of 0.75 contact hours may be earned by learners who successfully complete this continuing professional development activity. USF Health, the accredited provider, acknowledges touchIME as the joint provider in the planning and execution of this CNE activity.

    This activity is awarded 0.75 ANCC pharmacotherapeutic contact hour.

    Date of original release: 19 October 2023. Date credits expire: 19 October 2024.

    If you have any questions regarding credit please contact cpdsupport@usf.edu.

    This activity is CE/CME accredited

    To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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    Topics covered in this activity

    Endocrine Oncology / Thyroid Disorders
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    This Activity Is Funded By:

    An independent medical education grant from Bayer HealthCare
    Pharmaceuticals Inc.
    This activity is jointly provided by USF Health and touchIME.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals.

    Date of original release: 19 October 2023. Date credits expire: 19 October 2024.

    Claim Credit
    touchEXPERT OPINIONS
    Practical considerations for personalized medicine in thyroid cancer: Which therapies are suited to particular patient profiles?
    0.75 CE/CME credit
    Question 1/5
    Which of the following statements best reflects current clinical understanding of the molecular pathophysiology of thyroid cancers?

    ATC, anaplastic thyroid cancer; DTC, differentiated thyroid cancer; MTC, medullary thyroid cancer.

    BRAF V600E mutation is among the top eight most frequent genetic alterations—occurring in over half (52%)—of all thyroid cancers;1 it is the most common (59.7%) mutation identified in DTC.2 RET fusions occur in approximately 10% of PTC —a type of DTC. RET point mutations occur in 98% hereditary and 50% of sporadic MTC cases.3 NTRK fusions have been reported in multiple thyroid cancer subtypes, including ATC, PTC, MTC and PDTC; predictive modelling analyses suggested over half (58%) of the NTRK fusions identified were predicted to be pathogenic.4

    Abbreviations

    ATC, anaplastic TC; DTC, differentiated TC; MTC, medullary TC; PDTC, poorly differentiated TC; PTC, papillary TC; TC, thyroid cancer.

    References

    1. Hofmann MC, et al. Endocr Relat Cancer. 2022;29:R173–90.
    2. Vodopivec DM, Hu MI. Ther Adv Mol Oncol. 2022;14:17588359221101691.
    3. Parimi V, et al. NJP Precis Oncol. 2023;7:10.
    4. Park JC, et al. JCO Precision Oncol. 2022;6:e2100442.
    Question 2/5
    Which of the following approaches would you use when testing for NTRK fusions in a patient with thyroid cancer (based on international consensus guidance on NTRK evaluation in solid tumours published in 2020)?

    MTC, medullary thyroid cancer; NGS, next-generation sequencing; PCR, polymerase chain reaction.

    The JSCO/ESMO/ASCO/JSMO/TOS international expert consensus guidance for tumour-agnostic treatment options in patients with solid tumours recommends NTRK fusion testing should be considered before or during the standard treatment of advanced solid tumours (such as thyroid cancer), preferably by RNA-based NGS, which is the recommended method for determining the presence of NTRK fusion(s).

    Abbreviations

    ASCO, American Society of Clinical Oncology; ESMO, European Society of Medical Oncology; JSCO, Japanese Society of Clinical Oncology; JSMO, Japanese Society of Medical Oncology; NGS, next-generation sequencing; TOS, Taiwanese Oncology Society.

    Reference

    Yoshino T, et al. Ann Oncol. 2020;31:861–72.

    Question 3/5
    Your patient has histologically confirmed, advanced, metastatic MTC. As the patient is ineligible for surgery but urgent treatment is needed, you are considering initiating systemic targeted therapy with cabozantinib. Which of the following next steps would you consider in the management of this patient?

    IHC, immunohistochemistry; MTC, medullary TC; NGS, next-generation sequencing; TC, thyroid cancer.

    Cabozantinib is a multikinase inhibitor demonstrating in vitro activity against multiple kinase receptors including: RET, MET, VEGFR1–3, KIT, TRKB, FLT-3, AXL, ROS1, TYRO3, MER and TIE-2. Current labelling does not require genomic testing/biomarker evaluation prior to treatment initiation in MTC.

    Abbreviations

    MTC, medullary TC; TC, thyroid cancer.

    Reference

    FDA. Cabozantinib PI. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2023/203756s011lbl.pdf (accessed 25 September 2023).

    Question 4/5
    Which of the following statements best summarizes the findings of a phase II trial (NCT01723202) evaluating dabrafenib monotherapy vs combination dabrafenib plus trametinib in radioiodine-refractory BRAF-mutated thyroid cancer?

    ATC, anaplastic TC; DTC, differentiated TC; MTC, medullary TC; TC, thyroid cancer.

    An open-label, randomized, phase II, multicentre trial evaluating dabrafenib monotherapy vs combination dabrafenib plus trametinib in adult patients (aged ≥18) years with BRAF-mutated, radioactive, iodine-refractory, progressive DTC determined that combination dabrafenib plus trametinib was not superior in efficacy (as determined by ORR as the primary endpoint) compared with dabrafenib monotherapy (ORR [RECIST 1.1]: 30% [n/N=8/27; 95% CI 14–51%] vs 35% [n/N=9/26 95% CI 17–56%], respectively).

    Abbreviations

    CI, confidence interval; DTC, differentiated TC; ORR, objective response rate; RECIST 1.1, response evaluation criteria in solid tumours version 1.1; TC, thyroid cancer.

    Reference

    Busaidy NL, et al. Thyroid. 2022;32:1184–92.

    Question 5/5
    Your patient is receiving larotrectinib for the treatment of advanced NTRK fusion-positive PTC. Your patient is worried about potential side effects. Based on meta-analyses of available phase I/II trial data for larotrectinib, how would you counsel this patient?

    PTC, papillary TC; TC, thyroid cancer; TRAE, treatment-related adverse event.

    Combined analysis (data cut-off 20 July 2022) of the TC cohorts in three clinical trials evaluating larotrectinib in patients with NTRK fusion-positive solid tumours (NCT02576431, NCT02122913, NCT02637687) reported TRAEs were predominantly grade 1 to 2. Grade ≥3 TRAEs were reported in two (7%) participants (n/N=2/30; anaemia and decreased lymphocyte count). There were no treatment discontinuations due to TRAEs.

    Abbreviations

    TC, thyroid cancer; TRAE, treatment-related adverse event.

    Reference

    Cabanillas ME, et al. J Clin Oncol. 2023;41(Suppl. 16):60.

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    This Activity Is Funded By:

    An independent medical education grant from Bayer HealthCare
    Pharmaceuticals Inc.
    This activity is jointly provided by USF Health and touchIME.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals.

    Date of original release: 19 October 2023. Date credits expire: 19 October 2024.

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