Aumolertinib with carboplatin–pemetrexed versus aumolertinib for nonsmall cell lung cancer with <i>EGFR</i> and concomitant tumor suppressor genes (ACROSS2): An open‐label, multicenter, randomized phase 3 study
Abstract
ABSTRACT Third‐generation epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR‐TKIs) are standard first‐line therapy for advanced, EGFR ‐mutated nonsmall cell lung cancer (NSCLC). However, their benefit is limited in patients who have co‐existing tumor suppressor gene (TSG) mutations, highlighting a need for intensified strategies to improve outcomes. ACROSS2 (ClinicalTrials.gov identifier NCT04500717) is the first prospective, multicenter, randomized phase 3 study to compare the third‐generation EGFR‐TKI aumolertinib in combination with carboplatin–pemetrexed versus aumolertinib monotherapy in patients who had NSCLC with EGFR mutations and concomitant TSG mutations. In total, 126 patients were enrolled and randomly assigned to either combination therapy ( n = 62) or monotherapy ( n = 64). The primary end point was median progression‐free survival (PFS). At a median follow‐up of 25.3 months, combination therapy significantly prolonged median PFS compared with monotherapy (19.78 vs 16.53 months; hazard ratio, 0.58; 95% confidence interval, 0.34–0.97). Landmark PFS rates at 12, 18, and 24 months were 78.7% versus 65.3%, 67.2% versus 40.8%, and 41.0% versus 29.9%, respectively. Subgroup analyses demonstrated a clear PFS benefit in patients who had co‐existing tumor protein p53 ( TP53 ) mutations. Grade 3 or greater adverse events occurred in 25.9% of patients who received combination therapy versus 17.2% of those who received monotherapy; no drug‐related deaths were observed. Overall survival data were immature (data maturity, 4%). The ACROSS2 trial provides the first prospective evidence supporting a genotype‐directed, chemotherapy‐targeted intensification approach favoring aumolertinib plus carboplatin–pemetrexed for this molecularly defined population.
Article Details
Authors (26)
Jian‐Chun Duan
State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences Beijing China
Jia Zhong
State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences Beijing China
Bo‐Yang Sun
State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences Beijing China
Wen‐Hua Zhao
Department of Respiratory Oncology Guangxi Medical University Cancer Hospital Nanning China
Lin Wu
The Department of Thoracic Medical Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha China
Kai‐Lun Fei
State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences Beijing China
Qian Chu
Department of Oncology Tongji Hospital Huazhong University of Science and Technology Wuhan China
Qi‐Sen Guo
Department of Oncology Shandong Cancer Hospital Affiliated to Shandong University Jinan China
Qi‐Bin Song
Cancer Center Renmin Hospital of Wuhan University Wuhan China
Yan Yu
Department of Respiratory Oncology Harbin Medical University Cancer Hospital Harbin China
Da‐Xing Zhu
Lung Cancer Center West China Hospital Sichuan University Chengdu Sichuan China
Xin‐Yan Liu
Department of Oncology Hebei Chest Hospital Shijiazhuang China
Jun Zhao
Department of Thoracic Oncology Beijing Cancer Hospital Beijing China
Zhi‐Xiang Zhan
Department of Oncology Xinyang Central Hospital Xinyang China
Shi Li
Department of Oncology Shenyang Chest Hospital Shenyang China
Lei Nie
Department of Oncology Shanxi Provincial Cancer Hospital Xian China
Jie Lin
Department of Oncology The Second Affiliated Hospital of Kunming Medical University Kunming China
Xiao‐Dong Peng
Department of Oncology Chengdu Second People's Hospital Chengdu China
Dian‐Sheng Zhong
Department of Oncology Tianjin Medical University General Hospital Tianjin China
Jin Zhou
Department of Oncology Sichuan Cancer Hospital Chengdu China
Li‐Hua Li
Department of Oncology The First People's Hospital of Yunnan Province Kunming China
Yun‐Fang Chen
Department of Oncology Zhumadian Central Hospital Affiliated to Huanghuai University Zhumadian China
Chen Hu
Division of Quantitative Sciences Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore Maryland USA
Tony Mok
State Key Laboratory of Translational Oncology, Department of Clinical Oncology The Chinese University of Hong Kong Hong Kong Special Administrative Region Hong Kong China
Zhi‐Jie Wang
State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences Beijing China
Jie Wang
State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences Beijing China