Jamie E. Chaft, MD, FASCO, on Resectable EGFR-Mutated NSCLC: NeoADAURA Results

At ASCO 2025, I presented the primary results of the phase three NEOADAURA study. NEOADAURA is a randomized global three-arm study evaluating patients with resectable EGFR-mutant non-small cell lung cancer. The study randomized patients 1:1:1 to neoadjuvant osimertinib with chemotherapy, osimertinib monotherapy, or chemotherapy and placebo. The primary study endpoint was major pathologic response. The study fills a huge unmet need as currently our standard of care for patients with resectable lung cancer appropriate for neoadjuvant chemotherapy are treated with chemoimmunotherapy, and patients with EGFR-driven lung cancer are not appropriate for this approach. So we've been stuck with chemotherapy, unsure of the prospective efficacy. This randomized study showed that osimertinib with or without chemotherapy was statistically significantly better than chemotherapy and placebo in terms of inducing a major pathologic response defined as less than or equal to 10% viable tumor cells in the resection specimen. We also presented the early data for event-free survival, which while at only 15% maturity shows an early separation of the curves, which is encouraging. The reality was patients treated with what is our current standard of care chemotherapy preoperatively had a risk of progression not proceeding to surgery, accounting for the early difference in event-free survival. The safety was as expected for each individual agent and the combinations and there were no new concerning safety signals. We saw additional efficacy endpoints, increase in N2 nodal downstaging of 50% versus 20% as well as pathologic complete response visualized in the osimertinib arms, but didn't occur at all in the chemotherapy control arm. In my perspective, osimertinib fills an unmet need and should be considered with or without chemotherapy in the preoperative management of patients with resectable EGFR-mutant lung cancer for whom neoadjuvant therapy is recommended.