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Focus Questions
Why are tumour-agnostic approaches important in the advancement of precision oncology?
What examples are there of tumour-agnostic biomarkers and therapies?
How do HER2 alterations manifest in various solid tumours?
Why is HER2 an important tumour-agnostic biomarker?
How is HER2 status assessed in solid tumours?
What are some of the challenges associated with assessing HER2 status?
How might approval of the first HER2-directed tumour-agnostic therapy impact the way we treat solid tumours?
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Expanding the reach of HER2 in solid tumours: A spotlight on tumour-agnostic approaches

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Dr Dana Chase is an associate professor at the Division of Gynecologic Oncology in the Department of Obstetrics & Gynecology, David Geffen School of Medicine at the University of California in Los Angeles (UCLA), USA. read more

Dr Chase graduated with honours from Brown University in 1996. She went on to complete her medical degree in 2007, residency in obstetrics and gynaecology and gynaecologic oncology fellowship in 2011 at the University of California, Irvine. In 2011, Dr Chase joined the Division of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center in Phoenix.

Dr Chase’s expertise includes research and collaborative projects on scientific questions relating to quality of life, symptom management and supportive care. She is a member of NRG Oncology and a member of the following committees: Health Outcomes Research; Patient Centered Outcomes Research; Cancer Prevention and Control; Elderly; and the Data Monitoring Committee Panel A. 

Dr Chase is a fellow of the American Congress of Obstetricians and Gynecologists, as well as an active member of the Society of Gynecologic Oncology and American Society of Clinical Oncology. She is a reviewer for Gynecologic Oncology and the American Journal of Obstetrics and Gynecology. Dr Chase has authored more than 61 peer-reviewed articles along with over 45 abstracts dealing predominantly with the prevention and chemotherapy of gynaecologic malignancies and patient quality of life.

Dr Dana M. Chase discloses: Consultancy fees from AstraZeneca, Eisai, GSK and ImmunoGen. Other financial support from GSK. Speaker’s bureau fees from AstraZeneca, Eisai, GSK, ImmunoGen and Pfizer.

Learning Objectives

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

  • Discuss the implications of tumour-agnostic approaches in oncology and the role of tumour-agnostic biomarkers, such as HER2, across solid tumour types
  • Evaluate the use of HER2 as a tumour-agnostic biomarker in expanding the application of HER2-targeted therapies across various HER2-positive cancers
Overview

In this interview, Dr Dana Chase answers a series of questions on the tumour-agnostic potential of HER2 as a biomarker and its implications for the use of HER2-targeted therapies beyond the traditional boundaries of histological classification in oncology.

This activity is jointly provided by USF Health and touchIME.

Target Audience

This activity has been designed to meet the educational needs of oncologists, including head and neck cancer specialists, gastrointestinal oncologists and genitourinary oncologists involved in the management of solid tumours. 

USF Accreditation

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

Dr Dana M. Chase discloses: Consultancy fees from AstraZeneca, Eisai, GSK and ImmunoGen. Other financial support from GSK. Speaker’s bureau fees from AstraZeneca, Eisai, GSK, ImmunoGen and Pfizer.

Content reviewer

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

Touch Medical Contributors

Kathy Day 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 0.5 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.5 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.

Date of original release: 8 August 2024. Date credits expire: 8 August 2025.

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

EBAC® Accreditation

touchIME is an EBAC® accredited provider since 2023.

This programme is accredited by the European Board for Accreditation of Continuing Education for Health Professionals (EBAC®) for 0.5 hour of effective education time.

The Accreditation Council for Continuing Medical Education (ACCME®), and the Royal College of Physicians and Surgeons of Canada hold an agreement on mutual recognition on substantive equivalency of accreditation systems with EBAC®.

Through an agreement between the European Board for Accreditation of Continuing Education for Health Professionals and the American Medical Association (AMA), physicians may convert EBAC® CE credits to AMA PRA Category 1 CreditsTM. Information on the process to convert EBAC® credit to AMA credit can be found on the AMA website. Other health care professionals may obtain from the AMA a certificate of having participated in an activity eligible for conversion of credit to AMA PRA Category 1 CreditTM.

Faculty Disclosure Statement / Conflict of Interest Policy

In compliance with EBAC® guidelines, all speakers/chairpersons participating in this programme have disclosed or indicated potential conflicts of interest which might cause a bias in the presentations. The Organizing Committee/Course Director is responsible for ensuring that all potential conflicts of interest relevant to the event have been mitigated and declared to the audience prior to the CME activities.

Requirements for Successful Completion

Certificates of Completion may be awarded upon successful completion of the post-test and evaluation form. If you have completed one hour or more of effective education through EBAC® accredited CE activities, please contact us at accreditation@touchime.org to receive your EBAC® CE credit certificate. EBAC® grants 1 CE credit for every hour of education completed. 

Date of original release: 8 August 2024. Date credits expire: 8 August 2025.

Time to Complete: 30 minutes

If you have any questions regarding the EBAC® credits, please contact accreditation@touchime.org

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

Breast Cancer / Colorectal Cancer / Gastrointestinal Cancers / Lung Cancer
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Expanding the reach of HER2 in solid tumours: A spotlight on tumour-agnostic approaches
0.5 CE/CME credit

Question 1/5
You are discussing recent approvals of tumour-agnostic agents with your colleague. They ask you to explain how agnostic therapies in advanced/metastatic settings differ from standard treatment approaches for solid tumours. Which of the following explanations might you provide?

Tumours are usually enriched for one or more molecular alteration.1 Treating patients based on the mutations or alterations that drive tumour growth rather than the tumour origin and histological classification of disease can enable a more tailored approach to care, which could potentially lead to improvements in treatment outcomes.2 Additionally, these alterations (or biomarkers) can often predict response to therapy, further aiding in the optimization of therapeutic outcomes.1

References

  1. European Society for Medical Oncology. Oncology Pro. Tumour-agnostic treatments. Available at: https://oncologypro.esmo.org/oncology-in-practice/anti-cancer-agents-and-biological-therapy/targeting-ntrk-gene-fusions/overview-of-cancers-with-ntrk-gene-fusion/precision-medicine/tumour-agnostic-treatment (accessed 18 July 2024).
  2. Subbiah, V et al. CA Cancer J Clin. 2024;1–20. doi:10.3322/caac.21844
Question 2/5
Which of the following tests should be performed to determine whether a patient is eligible for HER2-directed therapy in a tumour-agnostic setting?

HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization; NGS, next-generation sequencing.

IHC testing is the most commonly used method for the clinical classification of HER2-positive tumours,1 and is essential for the use of HER2-targeted therapies in a tumour-agnostic setting.2 The CAP and ASCO have jointly issued specific guidance on IHC classification in breast and gastric cancers, in which it is recommended that IHC testing is followed by ISH if the IHC result is 2+ (equivocal) in non-tumour-agnostic settings.3–5

Abbreviations

ASCO, American Society of Clinical Oncology; CAP, College of American Pathologists; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization.

References

  1. Zhou Y, et al. Signal Transduct Target Ther. 2024;9:132.
  2. Fam-trastuzumab deruxtecan-nxki. Highlights of Prescribing Information, 2024. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2024/761139s028lbl.pdf (accessed 18 July 2024).
  3. Wolff AC, et al. J Clin Oncol. 2018;36:2105–22.
  4. Ivanova M, et al. Virchows Arch. 2024;484:3–14.
  5. Bartley AN, et al. J Clin Oncol. 2017;34:447–64.
Question 3/5
You are part of a team managing a 35-year-old man with unresectable biliary tract cancer. Biomarker testing reveals overexpression of HER2 (IHC 3+). Your colleague asks what this might mean for the patient’s disease trajectory and potential outcomes. How would you respond?

HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry.

HER2 is an emerging biomarker in solid tumour types such as biliary tract, bladder, cervical, colorectal, endometrial, ovarian and pancreatic cancers.1,2 HER2 overexpression is associated with an aggressive phenotype, poor prognosis, increased risk of recurrence and limited benefit from chemotherapy.1

Abbreviations

HER2, human epidermal growth factor receptor 2.

References

  1. Meric-Bernstam F, et al. J Clin Oncol. 2024;42:47–58.
  2. Yan M, et al. Cancer Metastasis Rev. 2015;34:157–64.
Question 4/5
You are managing a 53-year-old woman with pancreatic cancer and prior treatment with chemotherapy. Biomarker testing reveals a HER2 expression level of IHC 2+. Based on the current FDA-approved HER2-targeted tumour-agnostic therapies, what would you recommend for this patient?

FDA, US Food and Drug Administration; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NGS, next-generation sequencing.

HER2 overexpression can occur in a range of solid tumours, including breast, gastric, biliary tract, bladder, pancreatic and gynaecological tumours.1 HER2-overexpressing tumours are assessed using IHC testing to assess eligibility for HER2-targeted therapy.1 In the tumour-agnostic setting, only patients with unresectable or metastatic solid tumours and an IHC score of 3+ are eligible for treatment with a HER2-targeted agent.2 This is reflected in the latest NCCN guidelines for patients with pancreatic cancer.3

Abbreviations

FDA, US Food and Drug Administration; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NCCN, National Cancer Comprehensive Network; NGS, next-generation sequencing.

References

  1. Meric-Bernstam F, et al. J Clin Oncol. 2024;42:4–58.
  2. Fam-trastuzumab deruxtecan-nxki. Highlights of Prescribing Information, 2024. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2024/761139s028lbl.pdf (accessed 18 July 2024).
  3. NCCN Guidelines. Pancreatic Adenocarcinoma. Version 2.2024. www.nccn.org/ (accessed 18 July 2024).
Question 5/5
In the Phase II DESTINY-PanTumor02 trial, the tumour-agnostic activity of trastuzumab deruxtecan was assessed among patients with a variety of HER2-expressing solid tumours. Which cohort of patients demonstrated the greatest clinical benefits?

HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry.

The DESTINY-PanTumor02 assessed the efficacy and safety of trastuzumab deruxtecan at a dose of 5.4 mg/kg once every 3 weeks in patients with biliary tract, bladder, cervical, endometrial, ovarian, pancreatic and other tumours, who had locally advanced or metastatic disease after ≥1 systemic treatment or without alternative treatments. In the overall cohort, the ORR was 37.1%, median DOR was 11.3 months, median PFS was 6.9 months and median OS was 13.4 months. In the IHC 3+ cohort, the ORR was 61.3%, median DOR was 22.1 months, median PFS was 11.9 months and median OS was 21.1 months.

Abbreviations

DOR, duration of response; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

Reference

Meric-Bernstam F, et al. J Clin Oncol. 2024;42:4–58.

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