Martin Reck, MD, PhD, on Postsurgical MRD, Genomic Mutations, and Outcomes in Resectable NSCLC: AEGEAN Trial
2025 ASCO Annual Meeting
Martin Reck, MD, PhD, of LungenClinic Grosshansdorf, Germany, discusses data from the phase III AEGEAN trial that studied perioperative durvalumab and neoadjuvant chemotherapy. Patients who were MRD-positive after surgery had significantly worse disease-free survival compared to MRD-negative patients. In addition, mutations in KEAP1 and KMT2C were associated with MRD positivity and reduced benefit from the regimen, identifying a small high-risk subgroup with poor prognosis (Abstract 8009).
Transcript
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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.
The ASCO Post Staff
David Allen Barbie, MD, of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, reviews specific clinical and molecular features of early progressors and long-term progression-free survivors from the phase III ADRIATIC trial, which assessed consolidation durvalumab vs placebo after concurrent chemoradiotherapy for limited-stage small cell lung cancer (Abstract 8014).
The ASCO Post Staff
Andrew Kuykendall, MD, of Moffitt Cancer Center, discusses findings from the phase III VERIFY trial, which compared the efficacy of rusfertide vs placebo in patients with polycythemia vera who continue their current standard of care therapy (Abstract LBA3).
The ASCO Post Staff
Stuart J. Wong, MD, of the Medical College of Wisconsin and Plenary discussant, reviews findings from the phase III NIVOPOSTOP randomized trial, which investigated the adjuvant use of nivolumab added to radiochemotherapy for patients with resected head and neck squamous cell carcinoma who are at high risk of relapse (LBA2).
The ASCO Post Staff
Clifford A. Hudis, MD, FASCO, FACP, Chief Executive Officer of ASCO, discusses ASCO Guidelines Assistant, an AI-based collaboration between ASCO and Google Cloud which draws from ASCO’s evidence-based, published clinical practice guidelines, offering clinicians ready access to timely, trustworthy information.
The ASCO Post Staff
Alicia Latham, MD, MS, of Memorial Sloan Kettering Cancer Center, discusses the feasibility of using Pap-derived ctDNA for the detection of sporadic and Lynch syndrome–associated endometrial cancer (Abstract 10503).