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The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected  EGFR -mutant stage II–IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified ( TP53  exon4/5 mutations,  RB1  alterations, and copy number gains of  NKX2-1 ,  CDK4 , and  MYC ). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected  EGFR -mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes