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Poll

What method do you use to test for HER2 mutations in patients with advanced NSCLC?

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Next-generation sequencing
   
Sanger sequencing
   
Polymerase chain reaction
   
Other/do not test for HER2 mutations
   

Tutorial

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Poll

In which patients with advanced NSCLC do you consider using trastuzumab deruxtecan?

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Any HER2 alteration
   
HER2 mutations or HER2 overexpression
   
HER2 mutations only
   
Other/do not prescribe trastuzumab deruxtecan
   

Tutorial

This icon indicates there is a poll question. Click it when you see it to interact with your peers.

Poll

Which of these best describes your approach to HER2 testing in advanced solid tumours?

Submit your answer to see the results

I test all patients
   
I test when no other tx options available
   
I never test
   
Other
   
 
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Lung Cancer CE/CME accredited

touchPANEL DISCUSSION
A visually engaging discussion designed to emulate a ‘live’ panel experience and provide clinicians with practical expert insights to address their clinical challenges. Useful tips below will show how to navigate the activity. Close

Expanding HER2 horizons: Implications for NSCLC and beyond

  • Select in the video player controls bar to choose subtitle language. Subtitles available in English, Spanish.
  • A practice aid is available for this activity in the Toolkit
  • Downloads including slides are available for this activity in the Toolkit
Learning Objectives

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

  • Evaluate the clinical implications for tissue-agnostic HER2-targeted treatments for patients with advanced cancer
  • Discuss the latest data for HER2 targeting therapies in patients with advanced NSCLC and HER2 alterations
  • Outline best practices and guidelines for biomarker testing to establish HER2 status in patients with advanced NSCLC
Overview

In this activity, two medical oncologists and a pathologist discuss key considerations on tissue-agnostic HER2 targeting in solid tumours, the latest clinical trial data for approved and emerging HER2-targeted therapies in NSCLC, and best practices for testing for HER2 alterations in NSCLC.

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, pulmonologists and pathologists involved in the management of patients with solid tumours, including NSCLC.

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 Lyudmila Bazhenova discloses: Advisory board or panel fees from Abbvie, Anheart, AstraZeneca, Bayer, Bioatla, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Gilead, Janssen, Merck, Neuvogen, Novocure, Pfizer, Regeneron, Sanofi, Summit and Teligene (All Relationships Terminated). Consulting fees from Daichi and Pfizer (All Relationships Terminated).

Dr Razelle Kurzrock discloses: Grant/research support from Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda and TopAlliance. Advisory board/panel, consultant and speaker’s bureau fees from Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Inc., Biological Dynamics, Caris, CureMetrix, Daiichi, Datar Cancer Genetics, Eisai, EOM Pharmaceuticals, Iylon, LabCorp, Lanuaria, Merck, NeoGenomics, Neomed, Pfizer, Precirix, Prosperdtx, Regeneron, Roche, Turning Point Therapeutics, Volastra and X-Biotech. Support (royalties, patent, etc.) Dr Kurzrock is the co-founder and serves on the board of CureMatch.

Dr Ignacio Wistuba discloses: Advisory board or panel fees from Abbvie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Catalyst Therapeutics, Daiichi Sankyo, Flame, Genentech/Roche, Gl Therapeutics, Guardant Health, Janssen, Johnson & Johnson, Merck, Merus, Novartis, Oncocyte, Pfizer, Regeneron and Sanofi. Grants/research support from 4D, Adaptimmune, Adaptive, Akoya, Amgen, Bayer, Bristol Myers Squibb, EMD Serono, Genentech, Iovance, Johnson & Johnson, Karus, Medimmune, Merck, Novartis, Pfizer and Takeda. Speaker’s bureau fees from AstraZeneca, Genentech/Roche, Medscape, Merus, Merck, Pfizer and Platform Health.

Content reviewer

Danielle Walker, DNP, APRN, AGNP-C has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Contributors

Hannah Fisher 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.

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.

Date of original release: 25 September 2024. Date credits expire: 25 September 2025.

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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  • Select in the video player controls bar to choose subtitle language. Subtitles available in English, Spanish.
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  • Downloads including slides are available for this activity in the Toolkit

Topics covered in this activity

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touchPANEL DISCUSSION
Expanding HER2 horizons: Implications for NSCLC and beyond
0.75 CE/CME credit

Question 1/5
Your patient has advanced biliary tract cancer that has progressed following multiple lines of treatment, including durvalumab + gemcitabine + cisplatin and FOLFOX. You determine that there are limited satisfactory treatment options remaining for this patient. Which of the following would you test to guide the potential use of an agent with a tumour-agnostic approval?

BRCA1, breast cancer gene 1; FOLFOX, folinic acid, fluorouracil and oxaliplatin; HER, human epidermal growth factor receptor; PD-L1, programmed cell death ligand 1.

A recent tumour-agnostic indication for trastuzumab deruxtecan was approved by the FDA in adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options.1 The DESTINY-PanTumor02 trial reported an ORR of 56.3% in patients with biliary tract cancer with HER2 overexpression (IHC 3+).2 

Abbreviations

HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ORR, objective response rate.

References

  1. FDA. Trastuzumab deruxtecan PI. 2024. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2024/761139s028lbl.pdf (accessed 16 August 2024).
  2. Meric-Bernstam F, et al. J Clin Oncol. 2024;42:47–58.
Question 2/5
In the phase Ib element of the BEAMION-Lung1 trial, what ORR has been reported with zongertinib in patients with advanced HER2-mutated NSCLC?

HER2, human epidermal growth factor receptor 2; NSCLC, non-small cell lung cancer; ORR, objective response rate.

The phase I/II BEAMION-Lung1 trial of zongertinib in patients with advanced, unresectable and/or metastatic NSCLC reported an ORR of 74% in an interim futility analysis of the phase Ib element, which included 23 patients either pretreated or therapy naive (dependent on the cohort) with a HER2 mutation.1,2

Abbreviations

HER2, human epidermal growth factor receptor 2; NSCLC, non-small cell lung cancer; ORR, objective response rate.

Reference

  1. Heymach J, et al. Presented at: 2024 ASCO Annual Meeting, Chicago, IL, USA. 30 May– 3 June 2024. Abstr. 8514.
  2. ClinicalTrials.gov. NCT04886804. Available at: https://clinicaltrials.gov/study/NCT04886804 (accessed 28 August 2024).
Question 3/5
In the Destiny-Lung01 and Destiny-Lung02 trials investigating trastuzumab deruxtecan in patients with advanced HER2-mutated NSCLC, in what range were the ORRs for this patient cohort?

HER2, human epidermal growth factor receptor 2; ORR, objective response rate.

The phase II Destiny-Lung01 trial reported an ORR of 55% in patients with metastatic NSCLC harbouring activating HER2 mutations at a dose of 6.4 mg/kg (n=91),1 while the phase II Destiny-Lung02 reported an ORR of 56% at a dose 6.4 mg/kg (n=50) and 50% at a dose of 5.4 mg/kg (n=102).2

Abbreviations

HER2, human epidermal growth factor receptor 2; NSCLC, non-small cell lung cancer; ORR, objective response rate.

References

  1. Li BT, et al. N Engl J Med. 2022;386:241–51.
  2. Jänne PA, et al. Presented at: 2024 ASCO Annual Meeting, Chicago, IL, USA. 31 May–4 June 2024. Abstr. 8543.
Question 4/5
Your patient is newly diagnosed with stage IV metastatic NSCLC. You are aware of the need to test the patient for HER2 alterations to help inform treatment decisions. Based on NCCN guidelines, when would you perform these tests for this patient?

HER2, human epidermal growth factor receptor 2; ICI, immune checkpoint inhibitor; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer.

NCCN guidelines recommend molecular testing, including HER2, in patients with advanced or metastatic disease at clinical presentation.

Abbreviations

HER2, human epidermal growth factor receptor 2; NCCN, National Comprehensive Cancer Network.

Reference

NCCN. NSCLC. V7.2024. Available at: www.nccn.org (accessed 17 August 2024).

Question 5/5
You have sent tissue and plasma samples from your patient with newly diagnosed advanced NSCLC for molecular testing. You receive the results of the plasma testing, which is negative for all driver mutations. Assuming all options are feasible for this patient, what should you do next?

NSCLC, non-small cell lung cancer.

The NCCN guidelines recommend complete genotyping for EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET and HER2 via biopsy and/or plasma testing. Combinations of tissue and plasma testing, either concurrently or in sequence, are acceptable. However, negative results (meaning the absence of a definitive driver mutation) by one method suggests the use of a complementary method, and therefore in this situation the results of the tissue biopsy are required. 

Abbreviations

EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor 2; NCCN, National Comprehensive Cancer Network.

Reference

NCCN. NSCLC. V7.2024. Available at: www.nccn.org (accessed 17 August 2024).

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