A NEW post hoc analysis of the phase 3 ADAURA trial suggests that molecular residual disease (MRD) detection may help predict recurrence in patients with resected stage IB–IIIA EGFR-mutated non-small-cell lung cancer (NSCLC), raising the question of whether longer osimertinib therapy could improve outcomes. The findings indicate that MRD-positive patients may be at higher risk of recurrence, particularly after the standard 3-year adjuvant treatment period.
Researchers conducted an exploratory analysis of 220 patients from ADAURA, including 112 who received osimertinib and 108 who received placebo. MRD was assessed using tumour-informed circulating tumour DNA (ctDNA) and was compared with disease-free survival (DFS) events observed through imaging. The study aimed to evaluate whether MRD could serve as an early predictor of recurrence and whether patients who develop MRD positivity after stopping osimertinib might benefit from extended adjuvant therapy.
The results revealed that MRD positivity preceded DFS events by a median of 4.7 months (95% CI: 2.2–5.6). At 36 months, the DFS and MRD event-free rate was significantly higher in the osimertinib group (86%) compared to placebo (36%), with a hazard ratio of 0.23 (95% CI: 0.15–0.36). However, 25% of patients in the osimertinib group experienced DFS or MRD events, with most occurring after treatment cessation (68%) and within the first year of discontinuation (58%). At 24 months post-treatment, the DFS and MRD event-free rate had declined to 66%. These findings suggest that MRD could serve as an early indicator of recurrence risk, particularly after discontinuation of osimertinib.
MRD detection may help identify patients who could benefit from prolonged adjuvant osimertinib, though further clinical studies are needed to confirm its role in guiding treatment duration. These results highlight the potential of ctDNA-based MRD monitoring in optimising long-term management strategies for EGFR-mutated NSCLC.
Reference
Herbst RS et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer. Nat Med. 2025; DOI: 10.1038/s41591-025-03577-y.
