Targeted Therapies for Non-Small Cell Lung Cancer — Fifth Annual National General Medical Oncology Summit

Targeted therapies for HER2, RET, ALK, and ROS1 mutations in non-small cell lung cancer are shifting clinical practice, particularly regarding the use of tyrosine kinase inhibitors (TKIs) in adjuvant settings. While osimertinib and alectinib have established roles, clinicians are increasingly extrapolating these approaches to other targets, though randomized trials remain necessary for agents with significant toxicity profiles like MET and BRAF. Immunotherapy is largely ineffective in these oncogene-driven populations and is generally avoided. Trastuzumab deruxtecan and newer TKIs like lorlatinib and talotrectinib demonstrate robust intracranial activity, addressing the high risk of CNS metastasis. However, managing treatment-related toxicities—such as interstitial lung disease, hyperlipidemia, and neuropsychiatric effects—requires careful monitoring and multidisciplinary collaboration. Clinical decision-making now emphasizes shared patient-physician goals, especially when balancing the superior efficacy of newer agents against their distinct side-effect profiles.