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

• Published in: Nature communications Vol. 12; no. 1; p. 6450
• Main Authors: Liu, Si-Yang, Bao, Hua, Wang, Qun, Mao, Wei-Min, Chen, Yedan, Tong, Xiaoling, Xu, Song-Tao, Wu, Lin, Wei, Yu-Cheng, Liu, Yong-Yu, Chen, Chun, Cheng, Ying, Yin, Rong, Yang, Fan, Ren, Sheng-Xiang, Li, Xiao-Fei, Li, Jian, Huang, Cheng, Liu, Zhi-Dong, Xu, Shun, Chen, Ke-Neng, Xu, Shi-Dong, Liu, Lun-Xu, Yu, Ping, Wang, Bu-Hai, Ma, Hai-Tao, Yan, Hong-Hong, Dong, Song, Zhang, Xu-Chao, Su, Jian, Yang, Jin-Ji, Yang, Xue-Ning, Zhou, Qing, Wu, Xue, Shao, Yang, Zhong, Wen-Zhao, Wu, Yi-Long
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 49/23; 631/67/1059/602; 631/67/1612/1350; 631/67/69; 692/4028/546; 692/53/2423; Adjuvant therapy; Biomarkers; Biomarkers, Tumor - genetics; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Chemotherapy; Cisplatin - therapeutic use; Copy number; Disease-Free Survival; Epidermal growth factor receptors; ErbB Receptors - genetics; Gefitinib; Gefitinib - therapeutic use; Genomics; Humanities and Social Sciences; Humans; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; multidisciplinary; Mutants; Mutation; Myc protein; Non-small cell lung carcinoma; p53 Protein; Patients; Protein-tyrosine kinase; Science; Science (multidisciplinary); Small cell lung carcinoma; Subgroups; Survival; Thyroid transcription factor 1; Tumors; Tyrosine
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26806-7

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. Adjuvant gefitinib improves outcomes in non-small cell lung cancer (NSCLC) patients compared to chemotherapy, but not in all cases. Here, the authors find genomic biomarkers of response to gefitinib in NSCLC patients from the ADJUVANT trial, and propose a score to stratify them by potential benefit from the treatment.