Bo Zhang1, Jianlin Xu2, Xueyan Zhang3, Ping Gu4, Huimin Wang5, Shuyuan Wang6, Jie Qian7, Rong Qiao8, Yanwei Zhang9, Wenjia Yang10, Fangfei Qian11, Yan Zhou12, Jun Lu13, Lele Zhang14, Baohui Han15. 1. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: zb1063253078@163.com. 2. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: xujianlin1018@163.com. 3. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: zhangxueyan570@163.com. 4. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: anita.gu.ping@hotmail.com. 5. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: chestwhm@126.com. 6. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: 18817519225@163.com. 7. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: qianjie225@126.com. 8. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: qiaoxkyy@hotmail.com. 9. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: zhangyw198691@163.com. 10. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: 13764623117@163.com. 11. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: qianfangfei@outlook.com. 12. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: yzhou716@163.com. 13. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: lujun512@yahoo.com. 14. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: le91221@163.com. 15. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: 18930858216@163.com.
Abstract
OBJECTIVES: Occasionally, primary 20 T790M/insertion plus sensitive mutations can be detected within a single tumor sample by routine molecular testing, but the optimal clinical management for these patients is unclear. Herein, we determined the optimal treatment strategy for these patients. MATERIALS AND METHODS: From January 2011 to January 2017, patients diagnosed with epidermal growth factor receptor (EGFR) mutation were screened. For these harboring primary 20 T790M/insertion plus sensitive mutations, the effectiveness of the first or third generation tyrosine kinase inhibitors (TKIs) were retrospectively analyzed. RESULTS: 16,842 individuals were screened during the study period with 5900 positive patients identified. Sixty-one patients were confirmed to have primary 20 T790M/insertion plus sensitive mutations (1% of all EGFR-mutant patients, 95% CI, 0.8%-1.3%). Among them, 31 eligible patients were included for survival analyses. The median progression-free survival (PFS) of the 15 osimertinib-treated patients was 18.0 months (95% CI, 15.1-20.9 months), which was greatly longer than the 16 patients who were treated with first generation TKIs (1.2 months, 95% CI, 0.9-1.6, P < 0.001). Similar results were also observed in overall survival (OS) with 25.1 months (95% CI, not calculable) in the osimertinib group and 17.3 months (95% CI, 9.3-25.4 months) in the first generation TKI group (P = 0.02). CONCLUSIONS: For patients harboring primary resistant and sensitive mutations detected by routine clinical methods, first generation TKIs are ineffective even with the presence of sensitive mutations. However, osimertinib shows great survival benefit, and thus, should be considered during the whole clinical management.
OBJECTIVES: Occasionally, primary 20 T790M/insertion plus sensitive mutations can be detected within a single tumor sample by routine molecular testing, but the optimal clinical management for these patients is unclear. Herein, we determined the optimal treatment strategy for these patients. MATERIALS AND METHODS: From January 2011 to January 2017, patients diagnosed with epidermal growth factor receptor (EGFR) mutation were screened. For these harboring primary 20 T790M/insertion plus sensitive mutations, the effectiveness of the first or third generation tyrosine kinase inhibitors (TKIs) were retrospectively analyzed. RESULTS: 16,842 individuals were screened during the study period with 5900 positive patients identified. Sixty-one patients were confirmed to have primary 20 T790M/insertion plus sensitive mutations (1% of all EGFR-mutant patients, 95% CI, 0.8%-1.3%). Among them, 31 eligible patients were included for survival analyses. The median progression-free survival (PFS) of the 15 osimertinib-treated patients was 18.0 months (95% CI, 15.1-20.9 months), which was greatly longer than the 16 patients who were treated with first generation TKIs (1.2 months, 95% CI, 0.9-1.6, P < 0.001). Similar results were also observed in overall survival (OS) with 25.1 months (95% CI, not calculable) in the osimertinib group and 17.3 months (95% CI, 9.3-25.4 months) in the first generation TKI group (P = 0.02). CONCLUSIONS: For patients harboring primary resistant and sensitive mutations detected by routine clinical methods, first generation TKIs are ineffective even with the presence of sensitive mutations. However, osimertinib shows great survival benefit, and thus, should be considered during the whole clinical management.