Clinical utility of molecular residual disease detection in early-stage resected EGFR-mutated non-small cell lung cancer
Abstract
Molecular residual disease (MRD), detected through circulating tumor DNA, has emerged as a promising biomarker for surveillance in patients with early-stage non-small cell lung cancer (NSCLC) following curative-intent resection. Here we report the MRD analysis from the phase 3 EVIDENCE trial, which includes patients with stage II–IIIA resected EGFR-mutated NSCLC who have received either adjuvant icotinib or chemotherapy. A total of 1,352 plasma samples from 175 patients are analyzed using the MinerVa Prime assay, a personalized tumor-informed MRD platform. At the landmark timepoint, MinerVa Prime detects MRD positivity in 35.8% (38/106) of patients with stage III disease and 14.7% (10/68) of patients with stage II disease, with a longitudinal positivity rate of 47.4%. MRD-positive status is significantly correlated with inferior disease-free survival (DFS), both at landmark (hazard ratio [HR]: 4.44, P < 0.001) and during longitudinal monitoring (HR: 7.82, P < 0.001). Icotinib confers DFS benefits over chemotherapy in both MRD subgroups, enhancing MRD clearance in MRD-positive patients while reducing molecular recurrence in landmark MRD-negative patients. Longitudinal MRD shows a 91.3% negative predictive value, with a median lead time of 169 days prior to clinical recurrence. Among serial monitoring timepoints, MRD status at 24 weeks post-randomization demonstrates the highest prognostic value. For patients with resected EGFR-mutated lung cancer, effective strategies to guide post-surgical surveillance remain an unmet need. Here, the author shows that a personalized blood test may indicate molecular residual disease months before radiological progression.
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Institutions: First Affiliated Hospital Zhejiang University, Fudan University, Zhongshan Hospital, Fujian Medical University, Chinese PLA General Hospital, Union Hospital, Soochow University, Harbin Medical University, Guangzhou Medical University, Tongji Hospital, Shanghai East Hospital, First Affiliated Hospital of Xiamen University, Shantou University, Cancer Hospital of Shantou University Medical College, Capital Medical University, Jilin University, First Affiliated Hospital of Soochow University, Zhejiang Cancer Hospital, Third Affiliated Hospital of Harbin Medical University, First Affiliated Hospital of Guangzhou Medical University, Shanghai Pulmonary Hospital, First Affiliated Hospital of Zhengzhou University, Hunan Cancer Hospital, The First People's Hospital of Changde, Anhui Provincial Hospital, First Affiliated Hospital of Xi'an Jiaotong University, First Hospital of Jilin University, The First People's Hospital of Changzhou, Jiangsu Cancer Hospital, Genecast (China), Nantong Tumor Hospital, Fuzhou Pulmonary Hospital of Fujian, Beijing Chest Hospital, ShenZhen People’s Hospital, Betta Pharmaceuticals (China)