According to a pre-specified exploratory analysis with an ultra-sensitive circuating tumor (ct) DNA-based molecular residual disease (MRD) from the phase 3 NeoADAURA trial, baseline MRD status was found to be prognostic for clinical outcomes and pre-surgical MRD-negativity and clearance were associated with major pathological response (MPR).

These data will be presented by Collin Blakely, MD, PhD, University of California, San Francisco, California, at the 2025 IASLC World Conference on Lung Cancer in Barcelona, Spain. 

In this study, 358 patients with resectable EGFR-mutated stage II to IIIB NSCLC with a performance status of ≤ 1, of which 189 had evaluable MRD panes and were included in this analysis. Patients were randomized on a 1-to-1-to-1 basis to receive either 80 mg of once daily neoadjuvant osimertinib for ≥ 9 weeks plus cisplatin or carboplatin with pemetrexed once every 3 weeks for 3 cycles (n = 61), osimertinib monotherapy (n = 64), or placebo plus cisplatin or carboplatin with pemetrexed (n = 64) followed by surgical resection. Personalized tumor-informed MRD panels were used to assess baseline and pre-surgical plasma samples for MRD-positivity (n = 134) or MRD-negativity (n = 55). 

At analysis, the hazard ratio for event-free survival was 0.24 among MRD-negative patients and 0.80 among MRD-positive patients. In the osimertinib plus chemotherapy arm, the baseline MRD-positivity rate was 77% and the pre-surgical MRD-positivity rate was 23%. In the osimertinib monotherapy arm, the baseline MRD-positivity rate was 72% and the pre-surgical MRD-positivity rate 23%. In the placebo plus chemotherapy arm, the baseline MRD-positivity rate was 68% and the pre-surgical MRD-positivity rate was 53%. MRD clearance rates were 83%, 84%, and 58%, respectively. MPR was achieved in 20% of patients with MRD-negativity and 9% of patients with MRD-positivity. MPR was achieved in 24% of patients with MRD clearance and 6% of patients with non-clearance. 

“The tumour-informed, ctDNA-based MRD assay had a greater tumour detection rate vs. single EGFR gene mutation testing,” concluded Dr Blakely et al. “Baseline MRD status was prognostic for clinical outcomes” and “pre-surgical MRD[negativity] and clearane were associated with MPR.” They noted “Longer follow-up will determine how MRD status may guide treatment decisions in this setting."

Source:

Blakely C, Robichaux J, Lee SY, et al. Molecular residual disease (MRD) analysis from NeoADAURA: Neoadjuvant osimertinib ± chemotherapy in resectable EGFRm NSCLC. Presented at the 2025 IASLC World Conference on Lung Cancer. September 6-9, 2025. Barcelona, Spain. Abstract OA02.02