Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes
Si‐Yang Liu, Hua Bao, Qun Wang, Weimin Mao, Yedan Chen, Xiaoling Tong, Song-Tao Xu, Lin Wu, Yucheng Wei, Yong-Yu Liu, Chun Chen, Ying Cheng, Rong Yin, Fan Yang, Shengxiang Ren, Xiaofei Li, Jian Li, Cheng Huang, Zhidong Liu, Shun Xu, Ke‐Neng Chen, Shidong Xu, Lunxu Liu, Ping Yu, Buhai Wang, Haitao Ma, Hong‐Hong Yan, Song Dong, Xu‐Chao Zhang, Jian Su, Jin‐Ji Yang, Xue‐Ning Yang, Qing Zhou, Xue Wu, Yang Shao, Wen‐Zhao Zhong, Yi‐Long Wu
Abstract
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.