Martin Reck, MD, PhD, on Postsurgical MRD, Genomic Mutations, and Outcomes in Resectable NSCLC: AEGEAN Trial

It's my pleasure to present here at the ASCO meeting the data of the MRD analysis from the AEGEAN trial in patients with resectable non-small cell lung cancer. While in the AEGEAN trial perioperative durvalumab with neoadjuvant chemotherapy improved event-free survival and pCR compared to chemotherapy alone, furthermore, we collected plasma samples during treatment, during the neoadjuvant therapy, before and after surgery, and at the adjuvant treatment. Here at ASCO, we reported data on patients who were MRD positive after surgery assessed by the ctDNA analysis. When we look at the biomarker-available population, 10% of the MRD-available patients were MRD positive, and when we look at patients' characteristics, these were mostly patients with locally advanced non-small cell lung cancer, patients with mediastinal lymph node metastasis. Compared to the MRD-negative patients, the MRD-positive patients had worse outcomes in terms of disease-free survival. We do see a trend favoring durvalumab versus placebo also in these patients. However, the trend was small. Furthermore, we looked at the genetic features of the patients who were diagnosed with MRD positivity in the ctDNA-available patients. We performed a whole exome analysis and in the 17 MRD-positive patients we found a number of mutations which do have an impact on IO response including KMT2C and the KEAP1 mutation. Therefore, in summary, what we have seen in this MRD analysis is that 10% are MRD positive. These patients do have a worse prognosis, and the whole exome analysis did show an association between certain mutations including KEAP1 and KMT2C and the MRD positivity. The numbers were small. However, this is a very important result which requires further investigation, because we have identified a poor prognostic group of patients with probably no benefit from the immunotherapy.