Comparing Safety Profiles and Future Directions in HER2-Targeted Therapy

In this closing episode, Dr Julia Rotow compares the safety considerations associated with HER2-directed ADCs and TKIs and discusses how these profiles influence sequencing strategies. She outlines the cytotoxic-related adverse events commonly observed with ADCs—such as cytopenias, gastrointestinal symptoms, and alopecia—as well as the need for supportive care and early monitoring for pulmonary toxicity. She then reviews the adverse event patterns associated with HER2 TKIs, noting that each agent has a distinct tolerability profile informed by its degree of selectivity, with common toxicities including rash, diarrhea, and liver enzyme elevations. The episode also introduces emerging HER2 TKIs in development, including sevabertinib, and discusses ongoing randomized studies designed to clarify their role in earlier lines of therapy. Dr Rotow concludes by reflecting on the rapidly evolving treatment landscape and the need for comprehensive biomarker assessment to ensure that patients with HER2-altered NSCLC can access appropriate targeted therapies.