Expanding Adjuvant Targeted Therapy Beyond EGFR and the Promise of Neoadjuvant Approaches in NSCLC

Dr. Herbst asks Dr. Kareff about other targetable alterations now supported by adjuvant therapy data in NSCLC. Dr. Kareff describes the field as mirroring NCCN and ASCO guidelines across multiple biomarker-driven indications. He highlights the alectinib adjuvant data presented by Dr. Ramalingam at ASCO 2024 following chemoradiation, adjuvant selpercatinib data presented at ASCO 2026, and emerging investigation of adjuvant TKI therapy for patients with HER2 mutations currently in various trials. He frames this as the broader precision oncology revolution, where identifying a mutation obligates clinicians to treat it aggressively across the disease continuum.

Dr. Herbst raises neoadjuvant targeted therapy as a growing area of interest, noting its potential to shrink tumors before surgery, enable less extensive operations, and potentially improve long-term outcomes. Dr. Kareff describes discussing neoadjuvant osimertinib (NeoADAURA approach) at his tumor board, though he has not yet embarked on this with a patient given access limitations in his hybrid community-academic setting. NeoADAURA demonstrated major pathologic response rates of approximately 26% with neoadjuvant osimertinib compared with approximately 2% with placebo. He notes that the critical unanswered question remains whether pathologic response translates into durable survival improvement, drawing a parallel to questions that existed even before ADAURA's long-term data emerged.

Dr. Herbst describes using neoadjuvant osimertinib selectively in cases where tumor anatomy might require more extensive surgery; in these cases, close monitoring and planning for continued adjuvant targeted therapy afterward are essential. He reiterates the importance of using the best available targeted agents as early in the disease course as possible, and of building longitudinal databases to capture long-term outcomes across perioperative and adjuvant settings.