About the Study: Which patient populations with non–small cell lung cancer (NSCLC) with a mutation in the epidermal growth factor receptor (EGFR) would benefit from a first-line treatment of an intensified combination therapy? In this randomized phase 3 study including 294 patients with advanced NSCLC and an EGFR mutation and concurrent TP53 mutations, first-line osimertinib plus chemotherapy significantly improved median progression-free survival compared with osimertinib alone (34.0 months vs 15.6 months; hazard ratio for disease progression or death, 0.44). This study provides evidence for incorporating TP53-based molecular risk stratification into first-line clinical decision-making because the efficacy of intensified combination therapy justifies the added treatment-related burden in this high-risk population.
Corresponding Authors: Hongyun Zhao, MD (zhaohy@sysucc.org.cn), Yunpeng Yang, MD (yangyp@sysucc.org.cn), and Li Zhang, MD (zhangli@sysucc.org.cn), Dongfeng East Rd 651, Guangzhou 510060, Guangdong, China.
10.1001/jama.2026.10599
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