HER2-Altered Non-Small Cell Lung Cancer — 5-Minute Journal Club: Microlearning Activity 3

Management of HER2-altered non-small cell lung cancer (NSCLC) is evolving rapidly with the integration of HER2-directed antibody-drug conjugates like trastuzumab deruxtecan (T-DXd) and novel tyrosine kinase inhibitors (TKIs) such as zongertinib and sevabertinib. Clinical data from the DESTINY-Lung02 trial demonstrate that 5.4 mg/kg of T-DXd offers superior efficacy and a more favorable safety profile compared to higher doses, particularly regarding interstitial lung disease. While ctDNA serves as a valuable tool for monitoring resistance mechanisms and disease burden, it does not yet guide treatment holidays. Ongoing research, including the PANTUMOR-1 study, evaluates the efficacy of these targeted therapies across various histologies and HER2-mutant populations. Furthermore, the field is shifting toward earlier intervention in adjuvant and neoadjuvant settings, with a focus on mitigating toxicities like GI distress and pneumonitis to maintain patient quality of life.