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HER2 Altered NSCLC

CE / CME

HER2-Directed ADCs in HER2-Mutant and HER2-Overexpressing NSCLC

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Nurse Practitioners/Nurses: 1.00 Nursing contact hour

Released: March 18, 2026

Expiration: September 17, 2026

Matthew Gubens
Matthew Gubens, MD, MS, FASCO
Estelamari Rodriguez
Estelamari Rodriguez, MD, MPH
CME/CE Information

Activity

Progress
1 2 3
Course Completed

Introduction

In this module, Matthew Gubens, MD, MS, FASCO, and Estelamari Rodriguez, MD, MPH, review the rationale for targeting HER2 in non-small-cell lung cancer (NSCLC), optimal testing strategies for HER2, and data on HER2-directed antibody–drug conjugates (ADCs) in NSCLC as well as the practical applications of HER2-targeted therapy and emerging HER2-directed approaches in NSCLC. These topics were presented by Dr Gubens and Dr Rodriquez during a previously held virtual-live webinar titled, “Unlocking the Full Potential of HER2-Directed ADCs in HER2-Mutant and Overexpressing Lung Cancer: Testing Applications, Data Insights, and Effective Decision-making for Patient-Centric Care.”

Please note that the key points discussed in this module are illustrated with thumbnails from accompanying downloadable PowerPoint slidesets, which can be found here or downloaded by clicking any of the slide thumbnails in the module alongside the expert commentary.

Decera Clinical Education plans to measure the educational impact of this activity. A few questions will be asked twice: once at the beginning of the activity and then again after the discussion that informs the best choice. Your responses will be aggregated for analysis, and your specific responses will not be shared.

Before continuing with this educational activity, please take a moment to answer the following questions.

How many people with lung cancer do you provide care for in a typical month?

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

Which of the following is an indication for trastuzumab deruxtecan (T-DXd) in patients with advanced NSCLC who have received a prior systemic therapy?

Case History

A 67-year-old man with a remote history of smoking (<5 pack-year) presents with persistent cough, weight loss, and right upper quadrant pain. Imaging reveals a lung mass and liver and bone lesions; all are positive on PET/CT. A biopsy of the liver lesion confirms lung adenocarcinoma (TTF-1 and Napsin A+). Tissue next-generation sequencing shows a TP53 mutation, and PD-L1 tumor proportion score is 60%. He was treated with a platinum doublet and immunotherapy. After initial response lasting 6 months, he now shows progression in the liver. The patient has an Eastern Cooperative Oncology Group performance status of 1, mildly elevated liver enzymes, and no other comorbidities. Retesting on the original biopsy showed HER2 immunohistochemistry (IHC) 3+ and MET IHC 0 expression.

Which of the following is the most appropriate second-line treatment for this patient?

Case History

The patient is a 65-year-old woman with HER2 mutation–positive lung cancer with bilateral pulmonary nodules and bone metastases. She received carboplatin/pemetrexed/pembrolizumab as first-line therapy with a good partial response initially. Seven months later, she developed headaches and is found to have brain metastases; she started treatment with T-DXd at 5.4 mg/kg. She achieved a good partial response (resolution of brain metastases) but developed grade 2 nausea and vomiting. Because of refractory nausea despite antiemetics, the dose of T-DXd was reduced after cycle 6 to 4.4 mg/kg, and this was followed by improvement in nausea. After cycle 12, she reported acute worsening dyspnea and cough.

At a follow-up visit, she presents with shortness of breath related to her NSCLC. CT scan reveals new worsened right lower lobe infiltrate. Other causes of toxicities to the lungs, toxicities associated with the use of other concomitant medications, and other pathologies such as infection or pulmonary embolism are ruled out. The patient is referred to pulmonologist for further tests. On restaging using high-resolution CT, scattered ground-glass opacities are reported in both lungs. She is asymptomatic and has normal vital signs, including oxygen saturation of 98%. With the involvement of a pulmonologist, she is diagnosed with grade 1 interstitial lung disease (ILD).

At this time, what would you recommend for this patient with asymptomatic (grade 1) ILD?

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