Treatment Sequencing in HER2-Mutated NSCLC: First-Line and Beyond

In this segment, Drs. Santos and Lopes explore treatment sequencing strategies for patients with HER2-mutated NSCLC, a rapidly evolving area of clinical decision-making. The discussion addresses the current positioning of HER2-targeted therapies relative to chemotherapy and immunotherapy, particularly in the first-line setting.

Historically, patients with HER2 mutations were treated with standard platinum-based chemotherapy ± immunotherapy due to a lack of targeted options. However, with the emergence of effective ADCs, there is increasing interest in earlier-line integration of HER2-targeted therapy.

Key considerations include patient characteristics, disease burden, and the relative efficacy of available regimens. The speakers also discuss the limited benefit of immunotherapy in oncogene-driven NSCLC, a well-recognized pattern seen across multiple molecular subsets, including HER2.

The conversation highlights ongoing clinical trials evaluating HER2-targeted therapies in the first-line setting, which may further shift treatment paradigms. The importance of individualized treatment planning is emphasized, particularly as new data continue to emerge.

Sequencing decisions must balance efficacy, toxicity, and evolving evidence, with a clear trajectory toward increased use of targeted therapies earlier in the disease course.