AEGEAN: Analysis Explores Impact of Post-Surgical MRD Status in NSCLC

Certain patients with resectable non-small cell lung cancer (NSCLC) may not benefit from perioperative durvalumab plus neoadjuvant chemotherapy, according to exploratory analyses of the AEGEAN trial presented at the 2025 American Society of Clinical Oncology Annual Meeting.

In the phase 3 study, the combination significantly improved event-free survival (EFS) and pathological complete response (pCR) compared with neoadjuvant chemotherapy alone in patients with stage II-IIIb NSCLC who had an Eastern Cooperative Oncology Group Performance Status of 0 or 1.

However, previous analyses have suggested that patients without circulating tumor DNA (ctDNA) clearance during neoadjuvant treatment or with molecular residual disease (MRD) after surgery had worse outcomes.

A team of researchers, led by Martin Reck, MD, PhD, of Lung Clinic Grosshansdorf in Grosshansdorf, Germany, evaluated the regimen’s efficacy based on post-surgery MRD status, neoadjuvant ctDNA dynamics, pathological response, genomic mutations, and outcomes.

Their analysis identified a small high-risk subgroup of patients with worse prognosis who have a potentially reduced benefit from the AEGEAN regimen.

At a median 6.9 weeks post-surgery, 10% of patients were MRD-positive (durvalumab: n=10; placebo: n=7) and 90% were MRD-negative (durvalumab: n=78; placebo: n=73). Most of the MRD-positive patients (88%) had received a stage III NSCLC diagnosis. In addition, nine of the MRD-positive patients in the durvalumab arm also had ctDNA detected before surgery.

In the durvalumab arm, none of the MRD-positive patients achieved pCR or major pathological response.

Furthermore, the researchers observed worse disease-free survival (DFS) rates among patients who were MRD-positive. At 12 months, the overall DFS was 14.3% for MRD-positive patients compared with 89.3% for MRD-negative patients. Moreover, this was true in both the durvalumab and placebo arms. However, in the MRD-positive patients, DFS rates were better in those who were treated with durvalumab versus placebo.

In the durvalumab arm, KEAP1 and KMT2C were associated with MRD positivity. While there was no EFS benefit among patients with mutations in either arm, those with wild type (KEAP1wt) showed EFS benefit.