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Case Challenge: Treatment Strategies for a 72-Year-Old Woman With Newly Diagnosed HER2-Overexpression and PD-L1–Positive Metastatic NSCLC

Case Challenge
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This activity is available for 1.00 CME/CE credit(s).

Released: August 25, 2026

Expiration: February 24, 2027

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HER2 has emerged as an important biomarker and therapeutic target in NSCLC, but its testing and clinical interpretation remain complex. Distinguishing HER2 mutations from HER2 gene amplification and protein overexpression is essential for identifying eligible patients and appropriately selecting and sequencing therapy. This interactive case will examine comprehensive HER2 testing and interpretation, treatment selection and sequencing for HER2-overexpressing NSCLC, and the recognition and management of trastuzumab deruxtecan–associated adverse events, including interstitial lung disease.

HER2 Overexpression NSCLC Case

Pre Assessment

Assess your current knowledge and clinical approach before beginning your Case Challenge.
1.

How many people with non-small-cell lung cancer (NSCLC) do you provide care for in a typical month?

2.

For those who practice in academic or community settings, please indicate your practice setting:

3.

Patients with which of the following HER2 alterations are eligible for enrollment on the ongoing phase III DESTINY-Lung06 trial evaluating first-line trastuzumab deruxtecan (T-DXd) plus pembrolizumab in patients with unresectable/metastatic non-squamous NSCLC?

4.

Which of the following testing approaches would comprehensively identify patients who may be candidates for HER2-directed therapy in the frontline or subsequent-line settings?

5.

A patient with HER2-overexpressing metastatic NSCLC who progressed on first-line chemoimmunotherapy achieves a partial response to T-DXd. Six months later, routine CT imaging reveals asymptomatic ground-glass opacities consistent with asymptomatic interstitial lung disease (ILD).

Which management approach best balances continued disease control with patient safety?