Endocrine Oncology, Thyroid Disorders CE/CME ACCREDITED Watch Time: 41 mins

touchEXPERT OPINIONS Personalized treatment of RET-altered thyroid cancers: What is the value of biomarker testing and targeted therapies?

Leading experts explain the value of biomarker testing and targeted therapies for the personalized treatment of RET-altered thyroid cancers

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Prof. Maria Cabanillas
University of Texas MD Anderson Cancer Center, Houston, TX, USA
Thyroid cancer epidemiology and treatment options: Where are we today?

Prof. Maria Cabanillas outlines the different types of thyroid cancer, their epidemiology and the range of multikinase and targeted kinase inhibitor therapies available for the management of thyroid cancer.

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In this interview Prof. Cabanillas answers the following questions:

  • Can you describe the different types of thyroid cancer and the epidemiology of the disease?
  • Can you outline the different multikinase inhibitors and their uses in the treatment of thyroid cancer?
  • What, in your experience, are the limitations of multikinase inhibitors in the treatment of thyroid cancer?
  • Can you outline the available targeted kinase inhibitors and their uses in the treatment of thyroid cancer?
  • Can you describe the adverse effects you have seen associated with targeted kinase inhibitors?

Prof. Maria Cabanillas is an Oncologic Endocrinologist and tenured Professor at the University of Texas MD Anderson Cancer Center in Houston, TX, USA. read more

As a clinician and clinical researcher, Prof. Cabanillas treats both early and advanced thyroid cancers, including anaplastic thyroid cancers (ATC). She led the effort to create a rapid response team for ATC and completed her service on the 2021 ATC Guidelines Committee for the American Thyroid Association that were recently published.

Prof. Maria Cabanillas discloses Advisory board or panel fees from Bayer, Eli Lilly and Exelixis. Consultancy fees from Bayer and Eli Lilly. Grant research/support from Genentech and Merck.

 
Dr Vivek Subbiah
University of Texas MD Anderson Cancer Center, Houston, TX, USA
A personalized approach to treating RET-altered thyroid cancers: How is biomarker testing key to improving outcomes?

Dr Vivek Subbiah explains the concept of RET alterations in thyroid cancer, the methods available to detect these biomarkers, and how detecting RET alterations can influence treatment decision making and patient outcomes.

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In this interview Dr Subbiah answers the following questions:

  • What is currently known about RET alterations in patients with thyroid cancer and how these alterations affect patient prognosis?
  • What methods are available to detect RET alterations and what, in your opinion, are the challenges faced by clinicians with each method?
  • What are the benefits of detecting RET alterations in patients with thyroid cancer and how can the information be used for treatment decision-making?

Dr Vivek Subbiah is the clinical medical director of the Clinical Center for Targeted Therapy at The University of Texas MD Anderson Cancer Center in Houston, TX, USA. read more

Dr Subbiah is also an associate professor, clinical trialist and physician investigator in the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center in Houston, TX, USA. 

Dr Subbiah is a major advocate for precision oncology. His national leadership roles continue to expand as the national principal investigator for the BRAF non-V600 alteration arm of the NCI-MATCH Precision Medicine Clinical Trial. His trial portfolio includes trials that target BRAF, MEK, RET, CDK, WNT, VEGF, mTOR and EZH2-EED pathways; novel immunotherapy combination trials GITR, TLR7/9, PD1 and WT1; and several first-in-human trials of antibody–drug conjugates, oncolytic viruses, intra-tumoral therapies and radiopharmaceuticals.

He has published over 150 peer-reviewed articles in several prestigious journals such as the New England Journal of Medicine, Journal of Clinical Oncology, JAMA Oncology, Cancer Discovery, Clinical Cancer Research and Lancet Oncology. 

Dr Vivek Subbiah discloses Advisory board or panel fees from Daiichi Sankyo, Eli Lilly/LOXO Oncology, Helsinn, Incyte, Medimmune, Novartis, QED Pharma, Relay Therapeutics, Roche and Signant Health. Consultancy fees from Daiichi Sankyo, Eli Lilly/LOXO Oncology, Helsinn, Incyte, Medimmune, Novartis, QED Pharma, Relay Therapeutics, Roche and Signant Health. Grant research/support from Abbvie, Agensys, Alfasigma, Altum, Amgen, Bayer, Berghealth, Blueprint Medicines Corporation, Boston Biomedical, Boston Pharmaceuticals, Celgene, D3, Dragonfly Therapeutics, Eli Lilly/LOXO Oncology, Exelixis, Fujifilm, GlaxoSmithKline, Helsinn Pharmaceuticals, Idera Pharma, Incyte, Inhibrx, Medimmune, Multivir, Nanocarrier, Northwest Biotherapeutics, Novartis, Pfizer, Pharmamar, Roche/Genentech, Takeda, Turning Point Therapeutics and Vegenics. Other financial or material support (royalties, patents, etc.) from Incyte and Pharmamar.

 
Dr Lori Wirth
Center for Head and Neck Cancers, Massachusetts General Hospital, Boston, MA, USA
The promise of targeted therapies for RET-altered thyroid cancers: What do the latest clinical data show?

Dr Lori Wirth reviews the latest efficacy and safety data on targeted tyrosine kinase inhibitor therapies for patients with RET-altered thyroid cancers, and their implications for clinical practice.

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In this interview Dr Wirth answers the following questions:

  • What does the latest clinical evidence tell us about the efficacy of pralsetinib in RET-altered thyroid cancers?
  • What does the latest clinical evidence tell us about the efficacy of selpercatinib in RET-altered thyroid cancers?
  • What can you tell us about the toxicity profiles of pralsetinib and selpercatinib, and how they compare with multikinase inhibitors?
  • What are the implications of the efficacy and safety data for pralsetinib and selpercatinib for daily clinical practice?

Dr Lori Wirth is The Elizabeth and Michael Ruane Chair of Endocrine Oncology and Medical Director of Massachusetts General Hospital’s Center for Head and Neck Cancers, Boston, MA, USA. read more

She is also an Associate Professor in Medicine at Harvard Medical School. In addition to overseeing the Center for Head and Neck Cancers, Dr Wirth co-directs Massachusetts General/Massachusetts Eye and Ear’s Advanced Thyroid Cancer Clinic. Dr Wirth received her BA from Brown University and her MD from Columbia’s College of Physicians and Surgeons. She trained at New York Presbyterian Hospital and Dana-Farber/Harvard Cancer Center.

Dr Wirth is an international authority in advanced thyroid cancer and head and neck oncology. Her research focuses on clinical trials and leveraging translational data to maximize the impact of trial outcomes. 

Dr Wirth has served as Chairperson of the International Thyroid Oncology Group, and sits on a number of national and international oncology committees, including the National Comprehensive Cancer Network (NCCN)’s Thyroid Committee and the American Board of Internal Medicine (ABIM)’s Medical Oncology Exam Committee.

Dr Lori Wirth discloses Advisory board or panel fees from Bayer HealthCare Pharmaceuticals, Blueprint Medicines, Eli Lilly and Exelixis. Consultancy fees from Eisai.

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Overview & Learning Objectives
Overview

In this activity, thyroid cancer specialists share their perspectives on key aspects of RET-altered thyroid cancers, including the epidemiology of the disease, the importance of biomarker testing and the latest data on targeted therapies for patients with RET alterations.

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

Target Audience

This activity has been designed to meet the educational needs of oncologists, oncology surgeons, endocrinologists, nuclear medicine physicians, radiologists, pathologists and oncology nurse specialists involved in the management of patients with 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 

Prof. Maria Cabanillas discloses Advisory board or panel fees from Bayer, Eli Lilly and Exelixis. Consultancy fees from Bayer and Eli Lilly. Grant research/support from Genentech and Merck.

Dr Vivek Subbiah discloses Advisory board or panel fees from Daiichi Sankyo, Eli Lilly/LOXO Oncology, Helsinn, Incyte, Medimmune, Novartis, QED Pharma, Relay Therapeutics, Roche and Signant Health. Consultancy fees from Daiichi Sankyo, Eli Lilly/LOXO Oncology, Helsinn, Incyte, Medimmune, Novartis, QED Pharma, Relay Therapeutics, Roche and Signant Health. Grant research/support from Abbvie, Agensys, Alfasigma, Altum, Amgen, Bayer, Berghealth, Blueprint Medicines Corporation, Boston Biomedical, Boston Pharmaceuticals, Celgene, D3, Dragonfly Therapeutics, Eli Lilly/LOXO Oncology, Exelixis, Fujifilm, GlaxoSmithKline, Helsinn Pharmaceuticals, Idera Pharma, Incyte, Inhibrx, Medimmune, Multivir, Nanocarrier, Northwest Biotherapeutics, Novartis, Pfizer, Pharmamar, Roche/Genentech, Takeda, Turning Point Therapeutics and Vegenics. Other financial or material support (royalties, patents, etc.) from Incyte and Pharmamar.

Dr Lori Wirth discloses Advisory board or panel fees from Bayer HealthCare Pharmaceuticals, Blueprint Medicines, Eli Lilly and Exelixis. Consultancy fees from Eisai.

Content reviewer

Nurse planner and peer reviewer Alicia Canalejo, APRN, has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Sola Neunie 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 1.0 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 1.0 Category 1 credit 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.

Nurses

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 1.0 contact hour 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 1.0 ANCC pharmacotherapeutic contact hour.

Date of original release: 16 March 2022. Date credits expire: 16 March 2023.

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

Learning Objectives

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

  • Distinguish between different types of thyroid cancers and describe therapies that are appropriate for their management
  • Plan a personalized approach to treatment of RET-altered thyroid cancers, including use of biomarker testing and novel targeted therapies
  • Evaluate the clinical trial data for novel targeted therapies for RET-altered thyroid cancers and apply it to clinical practice
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This Activity Is Funded By:

An educational grant from Blueprint Medicines and Genentech, a member of the Roche Group.
This activity is jointly provided by USF Health and touchIME.

The information provided by this CE 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 CE 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: 16 March 2022. Date credits expire: 16 March 2023.

This content is intended for healthcare professionals only. Please confirm that you are a healthcare professional.

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Question 1/4
What information about PTC would you give to newly diagnosed patients when explaining the epidemiology of the disease?

PTC, papillary thyroid cancer.
 Correct

PTC represents ~90% of all diagnosed thyroid cancers.1 The incidence of thyroid cancer is two to three times more common in women compared with men, and it is estimated that there will be 31,940 cases in women and 11,860 cases in men in the USA in 2022.2

Abbreviations

PTC, papillary thyroid cancer.

References

  1. Rossi ED, et al. Lancet Diabetes Endocrinol. 2021;9:193–4.
  2. American Cancer Society; Cancer Statistics Center. Thyroid. Available at: https://cancerstatisticscenter.cancer.org/?_ga=2.138871091.1682881696.1638803504-353821412.1637787931#!/cancer-site/Thyroid (accessed 25 January 2022).
Question 2/4
Which of the following statements describe how DNA-based PCR assays can be used in the detection of RET alterations?

MTC, medullary thyroid cancer; PCR, polymerase chain reaction.
 Correct

DNA-based PCR assays are used to identify single-nucleotide variations such as missense mutations. The technique is not capable of detecting alleles below a relative frequency of 15–20%, and lacks the capability to identify gene translocations. For these reasons, this technique is only acceptable in cases of known mutations in familial MTC. DNA-based PCR assays are not usually suitable to detect fusions due to the variability of possible breaking points and the limited number of primers. 

Abbreviations

MTC, medullary thyroid cancer; PCR, polymerase chain reaction.

Reference

Belli C, et al. Ann Oncol. 2021;32:337–50.

Question 3/4
Your 62-year-old male patient is diagnosed with RET-mutant metastatic MTC and requires systemic therapy. You recommend starting treatment with a selective RET inhibitor. Based on the results of the LIBRETTO-001 and ARROW trials, what would you tell your patient about the likelihood of responding to such a drug?

MTC, medullary thyroid cancer; ORR, overall response rate.
 Correct

Selpercatinib and pralsetinib are approved in the USA for the treatment of patients with advanced or metastatic RET-mutant MTC or RET fusion-positive thyroid cancer who require systemic therapy.1,2 In the latest phase I/II trial of selpercatinib, LIBRETTO-001, after a median follow-up of 9–17 months, the ORR in patients with RET-mutant MTC (n=310) was ~70%.3 In the latest phase  I/II trial of pralsetinib, ARROW, after a median follow-up of 11 months, the ORR in patients with RET-mutant MTC (n=76) was ~60–70%.4

Abbreviations

MTC, medullary thyroid cancer; ORR, overall response rate.

References

  1. Retevmo (selpercatinib) prescribing information. 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/213246s002lbl.pdf (accessed 9 February 2022).
  2. Gavreto (pralsetinib) prescribing information. 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/213721s004lbl.pdf (accessed 9 February 2022).
  3. Sherman EJ, et al. J Clin Oncol. 2021;39(Suppl. 15):6073.
  4. Subbiah V, et al. Lancet Diabetes Endocrinol. 2021;9:491–501.
Question 4/4
Your 44-year-old female patient with RET-mutant MTC, currently being treated with a selective RET inhibitor, has developed grade 3 hepatotoxicity. How would you manage this side effect in the first instance?

ALT, alanine transaminase; AST, aspartate aminotransferase; MTC, medullary thyroid cancer.
 Correct

The prescribing information for selpercatinib and pralsetinib recommends that treatment is withheld for patients who develop grade 3 or 4 hepatotoxicity, and that the patient’s ALT/AST is monitored weekly until resolution to grade 1 or baseline. It is also recommended to resume at a reduced dose. If hepatotoxicity recurs at grade 3 or higher, treatment should be discontinued.1,2

Abbreviations

ALT, alanine transaminase; AST, aspartate aminotransferase.

References

  1. Retevmo (selpercatinib) prescribing information. 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/213246s002lbl.pdf (accessed 9 February 2022).
  2. Gavreto (pralsetinib) prescribing information. 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/213721s004lbl.pdf (accessed 9 February 2022).
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