Navigating HER2-Mutant NSCLC Pathology and Management: A Webinar Preview With Helena A. Yu, MD, and Maria Arcila, MD

Advances in Detection of HER2 Alterations in NSCLC

HER2 alterations are now recognized as actionable biomarkers in NSCLC, with important implications for first-line and subsequent treatment. Dr. Arcila emphasizes that HER2 testing should not be isolated, but embedded within broad molecular profiling for all patients with advanced or metastatic NSCLC at the time of diagnosis.

“Oncologists should order testing for HER2 alterations as part of a broad molecular profiling for all patients with advanced or metastatic non–small cell lung cancer, and this is at the time of diagnosis,” she explains. Such an approach not only detects HER2 mutations but also identifies other targetable alterations, ensuring that precious biopsy material is used efficiently.

Practical Strategies for Community Testing

Recognizing the variability in access to next-generation sequencing (NGS), Dr. Arcila will address real-world constraints and solutions. Because resources may be limited at different institutions, she will outline bridging strategies using polymerase chain reaction (PCR)–based and multiplex assays when comprehensive NGS is not immediately accessible.

“The most important thing is to have an assay that is able to detect all of the alterations that are required,” she notes, stressing the need to choose technologies that use the least amount of DNA so that “you can test all of the biomarkers from a small biopsy.” The webinar will provide community teams with practical algorithms for stepwise testing—testing first for key alterations and then reflexing to broader profiling when initial results are negative.

Integrating New HER2-Directed Therapies Into Clinical Practice

Once HER2 mutations are identified, treatment decisions can be transformative. Dr. Yu underscores that more than half of patients with non–small cell lung cancer will have a driver mutation, and outcomes are “clearly better if their treatment matches their oncogene profile.”

She will review current HER2-directed agents, including trastuzumab deruxtecan, and highlight the impact of newer oral HER2-directed tyrosine kinase inhibitors. “Previously we had a good drug, trastuzumab deruxtecan, but it is an intravenous drug; so to have oral targeted therapies to give our patients, and to give them in the first line, is really an amazing thing for our patients,” Dr. Yu explains. The discussion will cover efficacy data, toxicities, and practical guidance on how to integrate these agents into first-line and subsequent lines of therapy.

What to Expect in the Webinar

When asked what messages they most look forward to sharing in the webinar, Dr. Yu said she is most eager to “highlight these new oral therapies—zongertinib and sevabertinib—how to give, them, what the efficacy is like, what the side effects are like, and how to integrate them into your practice.”

Dr. Arcila added, “From my side, I think it’s really important to recognize that although HER2 mutations are rare, they are a possibility for patients. It’s important to implement the testing and be able to identify these patients expeditiously so that you can treat them.”

Key Takeaways

• Broad molecular profiling at diagnosis is essential for all patients with advanced or metastatic NSCLC.
• HER2 mutations are actionable targets that can significantly influence first-line and subsequent treatment decisions.
• Practical testing strategies—including NGS and multiplex/PCR-based approaches—can be tailored to institutional resources while preserving limited tissue.
• The HER2 treatment landscape now includes trastuzumab deruxtecan and newly approved oral HER2-directed TKIs, expanding options for patients.
• Early, systematic testing and rapid integration of targeted therapies are critical to improving outcomes for patients with HER2-mutant NSCLC.

Be sure to register for the webinar on January 8th or January 26th to gain practical, clinic-ready insights on closing the gap between detection and optimal treatment in HER2-mutant NSCLC.