Recent advancements in the treatment of HER2-mutant non-small cell lung cancer (NSCLC) are focusing on targeted therapies, specifically tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs). Newer TKIs, such as zongertinib and sevabertinib, are demonstrating promising results, but exhibit distinct mechanisms and associated side effects.
Zongertinib is designed as a selective inhibitor of HER2, while sevabertinib targets both HER2 and epidermal growth factor receptor (EGFR).This dual inhibition by sevabertinib can lead to increased gastrointestinal side effects, attributable to EGFR blockade.Both drugs have shown meaningful objective response rates when used as second-line treatments for patients wiht HER2-mutated NSCLC.
A key distinction lies in patient eligibility.While tkis generally present a more manageable toxicity profile, ADCs currently have a broader approval scope. ADCs are approved for use in patients with tumors harboring HER2 mutations and those with HER2 protein overexpression – a difference that expands the potential patient population benefiting from targeted treatment.
Treatment decisions require careful consideration of individual drug toxicities and patient-specific factors,including pre-existing conditions like lung disease. Ongoing clinical trials are crucial to refine treatment sequencing and optimize outcomes as these novel therapies continue to evolve the landscape of HER2-mutant NSCLC treatment. As of January 21, 2026, clinical evaluation remains essential to determine the optimal use of these agents and their place in the broader treatment paradigm.
