At ESMO 2025, John Heymach presented this AEGEAN exploratory analysis during Mini Oral Session 2 — Non-metastatic NSCLC, outlining how CT-based radiomic features—alone and combined with on-treatment ctDNA—relate to pathological complete response (pCR) and event-free survival (EFS) in the perioperative durvalumab setting.
Background
AEGEAN previously showed that perioperative durvalumab plus neoadjuvant platinum chemotherapy improved event-free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in resectable NSCLC. Earlier analyses linked ctDNA clearance during neoadjuvant therapy to better EFS and pCR, and radiologic response in the durvalumab arm to pCR. This report evaluates whether radiomic features—with or without on-treatment ctDNA—can function as early-response biomarkers for pCR and EFS.
Methods
AEGEAN is a double-blind, placebo-controlled trial (NCT03800134). Treatment-naïve, stage II–IIIB(N2) resectable NSCLC patients were randomized 1:1 to neoadjuvant durvalumab or placebo every 3 weeks for 4 cycles, each with platinum chemotherapy, followed by adjuvant durvalumab or placebo every 4 weeks for 12 cycles after surgery. Radiomics were extracted from CT scans; the key feature was delta energy of the primary lung tumor from screening to pre-surgery. ctDNA was measured using patient-specific, tumor-informed assays. Predictive performance for pCR (AUC) and association with EFS (C-index; Cox models) were assessed for radiomics alone and for radiomics + C3D1 ctDNA status.
Results
Of 366 modified-intent-to-treat patients in the durvalumab arm, radiomics were available for 235 (rBEP); 111 of these also had C3D1 ctDNA (rcBEP_C3D1).
- Prediction of pCR: Radiomics AUC 0.78 (rBEP) and 0.82 (rcBEP_C3D1); radiomics + ctDNA AUC 0.84 (rcBEP_C3D1).
- Association with EFS: Radiomics C-index 0.668 (rBEP) and 0.708 (rcBEP_C3D1); radiomics + ctDNA C-index 0.787 (rcBEP_C3D1).
Conclusions
In AEGEAN, radiomic features, with or without on-treatment ctDNA, predicted pCR and showed a good association with EFS. The combination of radiomics + C3D1 ctDNA provided the strongest signal, supporting their potential as early-response biomarkers to guide perioperative immunochemotherapy strategies in resectable NSCLC.
You can read the full abstract here.