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HER2 Overexpression in NSCLC: From Testing to Treatment

Clinical Thought

The landscape of HER2-positive NSCLC has evolved to encompass HER2 mutations, HER2 gene amplification, and HER2 protein overexpression—distinct alterations that require different clinical management approaches. In this commentary, experts discuss the nuances of biomarker testing for HER2-mutated and HER2-overexpressing NSCLC and share how they currently approach treatment selection and sequencing.

Released: August 26, 2026

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Provided by Clinical Care Options, LLC dba Decera Clinical Education.

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Supporters

This activity is supported by educational grants from AstraZeneca and Daiichi Sankyo, Inc.

AstraZeneca

Daiichi Sankyo, Inc.

Target Audience

This program is intended for oncologists and other healthcare professionals caring for patients with NSCLC

Learning Objectives

Upon completion of this activity, participants should be able to:

  • Implement evidence-based strategies for accurate HER2 biomarker testing in NSCLC, including appropriate use of IHC, ISH, and NGS, to ensure consistent identification and reporting of HER2 overexpression and guide selection of HER2-directed therapies

  • Plan individualized sequencing strategies for HER2-overexpressing NSCLC using current evidence and patient-centered considerations

  • Devise proactive measures for monitoring and managing adverse events associated with HER2-directed ADCs and tailor salvage therapy for relapsed HER2-overexpressing NSCLC

Financial Disclosures

Primary Author

Benjamin Levy, MD, FASCO: consultant/advisor/speaker: AstraZeneca, DSI, Janssen, Merck, Pfizer, Takeda.

Helena Yu, MD: consultant/advisor/speaker: AstraZeneca, Blossom Hill, Bristol Myers Squibb, Daiichi Sankyo, Janssen, Summit, SystImmune, Taiho.

Additional Disclosures

Generative artificial intelligence (AI) tools were used for revising or refining educational content. All AI-assisted content underwent human review, editing, and validation by qualified faculty and accredited education staff to ensure scientific accuracy, balance, and compliance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education.