Incorporating Shared Decision-Making and Patient Preference in Treatment Choice for HER2-Mutation mNSCLC

Incorporating Shared Decision-Making and Patient Preference in Treatment Choice for HER2-Mutation Metastatic NSCLC

The rapid pace of therapeutic development in HER2-mutated non–small cell lung cancer (NSCLC), including recent approvals within weeks of clinical discussions, necessitates comprehensive patient education and shared decision-making approaches. Clinicians must present treatment options side by side, facilitating informed discussions about patient priorities, goals, and preferences when choosing between available second-line therapies. This patient-centered approach becomes particularly important given the distinct characteristics and administration requirements of different HER2-targeted options, allowing patients to participate actively in treatment selection based on their individual circumstances and values.

The practical differences between T-DXd and zongertinib significantly impact patient experience and quality-of-life considerations. T-DXd requires IV administration as an antibody-drug conjugate, necessitating peripheral IV access and more frequent clinical visits for monitoring. The therapy carries chemotherapy-like toxicities including nausea, vomiting, neutropenia, and interstitial lung disease risk, requiring closer surveillance with repeat echocardiograms to monitor for cardiac dysfunction and more frequent imaging (typically every 6-9 weeks initially). These factors contribute to increased health care utilization and potential impact on patient daily functioning.

In contrast, zongertinib offers the convenience of once-daily oral administration as a targeted tyrosine kinase inhibitor, though it requires patient adherence and specific monitoring protocols including liver function testing every 2 weeks for the first 12 weeks. After the initial monitoring period, patients experience fewer required clinical visits and standard imaging intervals of approximately 3 months. Patient-reported outcomes favor zongertinib, with higher improvements in functional status, respiratory symptoms including cough and dyspnea, and greater durability of symptomatic improvements. The cumulative toxicity profile of chemotherapy-based approaches vs the targeted nature of zongertinib represents a crucial consideration in treatment sequencing, supporting the preference for zongertinib followed by trastuzumab deruxtecan in clinical practice to optimize both efficacy and patient experience throughout the treatment continuum.