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Breast Cancer CME ACCREDITED Watch Time: 30 mins

touchTALKS Emerging HER-targeted antibody-drug conjugates for advanced breast cancer: What are we discovering?

Join Dr Judy King as she talks through the differences between novel antibody-drug conjugates and trastuzumab emtansine, and the latest data on these emerging therapies in the treatment of advanced breast cancer.

 
Emerging HER2-targeted ADCs: How do they differ from T-DM1?

Dr Judy King talks us through the structure of antibody-drug conjugate (ADC)s and how novel ADCs are utilising both the classical ADC mechanism of action and the bystander killing effect. She also briefly reviews novel human epidermal growth factor receptor (HER)2-targeted ADCs either recently approved or in development for the treatment of breast cancer and highlights how these therapies may provide additional treatment options for patients.

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Emerging HER2-targeting ADCs for advanced breast cancer: What do the data show?

Dr Judy King reviews the latest data on the use of novel HER2-targeted ADCs for the treatment of advanced breast cancer and discusses the management of adverse events.

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New ADCs and new targets: Looking to the future for advanced HER2+ and HER2-low breast cancer

Dr Judy King walks us through the latest data on the use of HER2-targeted ADCs in the treatment of HER2-low advanced breast cancer and reviews the development of novel therapeutics targeting HER3.

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Overview & Learning Objectives
Overview

In this activity, Dr Judy King, an expert in breast cancer, discusses the emerging human epidermal growth factor receptor (HER)-targeted antibody-drug conjugates (ADCs) in development for the treatment of breast cancer, and how these therapies may change clinical practice.

This activity has been jointly provided by Oakstone and touchONCOLOGY. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians.

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Target audience

This activity has been designed to meet the needs of oncologists, nurses and other healthcare professionals involved in the management of patients with breast cancer.

Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Faculty

Dr Judy King discloses: Advisory board/consultancy fees from Eisai, Eli Lilly and Company, Genomic Health, Novartis, Pfizer Inc. and Roche.

Content Reviewer

Walter Murray Yarbrough, MD has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Alison Scott has no financial interests/relationships or affiliations in relation to this activity.

Requirements for successful completion

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. A score of 70% or higher is needed to obtain CME credit. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

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 (AME). European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Date of original release: July 08, 2020. Date credits expire: July 08, 2021.

Learning Objectives

After watching this activity participants should be better able to:

  • Describe how the structure and mechanism of action of antibody-drug conjugates may address current unmet treatment needs in patients with advanced breast cancer
  • Evaluate clinical data for emerging anti-HER2 antibody-drug conjugates used to treat patients with HER2-positive advanced breast cancer
  • Discuss how clinical practice may change with the emergence of novel HER-targeted antibody-drug conjugates for patients with advanced breast cancer
Faculty & Disclosures
Dr Judy King

Royal Free London NHS Foundation Trust, London, UK

Judy King is a consultant medical oncologist at the Royal Free London NHS Foundation Trust in the UK. She qualified from Cambridge University and Guys and St Thomas’ School of Medicine and Dentistry in 2001 and completed a PhD in T cell immunotherapy of malignancies in 2008. During her specialty training, she also completed a Darzi Fellowship in Leadership and Management and completed a Postgraduate Certificate from Leeds Business School.
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Dr King’s main research interest is in combining chemotherapy and novel agents with immunotherapy and human epidermal growth factor receptor (HER)2-directed therapies. She also sits on the Joint Specialty Committee for Medical Oncology at the Royal College of Physicians and is Oncology Training Director for the Royal Free Hospital.
 

Disclosures: Advisory board/consultancy fees from Eisai, Eli Lilly and Company, Genomic Health, Novartis, Pfizer Inc. and Roche.

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Question 1/5
Which of the following is a component of an antibody-drug conjugate?
Correct

Antibody-drug conjugates are composed of a recombinant monoclonal antibody covalently bound to a cytotoxic drug payload via a synthetic linker.

References
Rinnerthaler G, et al. HER2 directed antibody-drug conjugates beyond T-DM1 in breast cancer. Int J Mol Sci. 2019;20:1115–32.

Question 2/5
Which of the following is a potential mechanism of action of human epidermal growth factor receptor 2-targeted antibody-drug conjugates?
Correct

HER2-targeted ADCs with cleavable linkers bind to HER2 expressed on the surface of tumour cells. The ADC-HER2 complex is internalised by endocytosis and the linker is cleaved by lysosomal proteases to release the cytotoxic payload, inducing cell death. ADCs can also be designed to release the cytotoxic payload to the extracellular space to kill surrounding and bystander cells, including HER2 negative cells. The bystander killing effect can occur when the cytotoxic payload is released from the ADC after binding to HER2 on the tumour cell and before internalisation, or through release of a highly membrane permeable drug payload from the tumour cell into the intracellular space.

Abbreviations
ADC, antibody-drug conjugate; HER2, human epidermal growth factor receptor 2.

References
Rinnerthaler G, et al. HER2 directed antibody-drug conjugates beyond T-DM1 in breast cancer. Int J Mol Sci. 2019;20:1115–32.

Question 3/5
Your patient is a 62-year-old woman with HER2-positive/HR-negative metastatic breast cancer. Based on current standards of care and the latest Phase II data, which other therapies should she have received before you consider treatment with a novel antibody-drug conjugate (assuming this treatment is available to you)?
Correct

Taxanes, trastuzumab and pertuzumab are the current recommended first-line options for the treatment of HER2-positive MBC. T-DM1 is a recommended second-line option where it is available.1,2 Trastuzumab deruxtecan is approved in USA for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting and in Japan for the treatment of patients with HER2-positive unresectable or recurrent breast cancer after prior chemotherapy.3,4

Abbreviations
ADC, antibody-drug conjugate; HER2, human epidermal growth factor receptor 2; MBC, metastatic breast cancer; T-DM1, trastuzumab emtansine.

References

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Breast Cancer. Version3. Invasive Breast Cancer. 2020;14–79.
  2. Cardoso F, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Annals Oncol. 2018;29:1634–57.
  3. Daiichi Sankyo Inc. ENHERTU®: fam-trastuzumab deruxtecan-nxki for injection, for intravenous use. Full prescribing information. 2019. Available at: https://dsi.com/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true (accessed 22 June 2020).
  4. Daiichi Sankyo Inc. (24 March 2020). ENHERTU® approved in Japan for treatment of patients with HER2 positive unresectable or metastatic breast cancer. 2020. Available at: www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/007103.html (accessed 22 June 2020).
Question 4/5
Biopsy results are back for your patient, a 53-year-old woman with advanced breast cancer. Which of the following would class as human epidermal growth factor receptor (HER)2-low metastatic breast cancer?
Correct

Although there is no formal definition of HER2-low metastatic breast cancer, it is currently considered to include breast carcinomas with a HER2 IHC score of 1+ or 2+ and lacking HER2 amplification.

Abbreviations
HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization.

References
Marchiò C, et al. Evolving concepts in HER2 evaluation in breast cancer: Heterogeneity, HER2-low carcinomas and beyond. Sem Cancer Biol. 2020;S1044-579X(20)30049-3.

Question 5/5
The biopsy results confirm that your 53-year old patient has HER2-low/HR-positive metastatic breast cancer. Her prior therapies include fluorouracil, epirubicin and cyclophosphamide, and anastrazole. What could you do next?
Correct

Trastuzumab deruxtecan is not yet approved for the treatment of HER2-low advanced breast cancer.1 The DESTINY-Breast04 Phase III clinical trial (NCT03734029) is recruiting patients with HER2-low unresectable and/or MBC.2

TULIP (NCT03262935) is an ongoing Phase III trial of trastuzumab duocarmazine in patients with HER2-positive unresectable locally advanced and/or MBC.3 T-DM1 has previously been shown to be less effective in patients with HER2-low advanced breast cancer.4

Abbreviations
ADC, antibody-drug conjugate; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; MBC, metastatic breast cancer; T-DM1, trastuzumab emtansine.

References

  1. Daiichi Sankyo Inc. ENHERTU®(2019) Full prescribing information: fam-trastuzumab deruxtecan-nxki for injection, for intravenous use. Full prescribing information. 2019. Available at: https://dsi.com/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true (accessed 22 June 2020).
  2. ClinicalTrials.gov. Trastuzumab deruxtecan (DS-8201a) versus investigator’s choice for HER2-low breast cancer that has spread or cannot be surgically removed [DESTINY-Breast04]. Available at: www.clinicaltrials.gov/ct2/show/NCT03734029 (accessed 4 June 2020).
  3. ClinicalTrials.gov. SYD985 vs physician’s choice in participants with HER2-positive locally advanced or metastatic breast cancer (TULIP). Available at: https://clinicaltrials.gov/ct2/show/NCT03262935 (accessed 22 June 2020).
  4. Yazaki S, et al. Lower response to T-DM1 in metastatic breast cancer patients with HER2 IHC score of 2 and FISH positive compared with IHC score of 3. Annals Oncol. 2017;28(Suppl. 5):v74–108.
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