Guangjian Yang1, Jun Li2, Haiyan Xu3, Yaning Yang1, Lu Yang1, Fei Xu1, Bing Xia4, Viola W Zhu5, Misako Nagasaka6, Yan Yang7, Yapin Li7, Weini Qiu7, Jianming Ying8, Sai-Hong Ignatius Ou5, Yan Wang9. 1. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan Nan Li, Chaoyang District, Beijing, 100021, China. 2. Center of Clinical Laboratory Medicine, Chinese People's Liberation Army General Hospital, No.28 Fuxing Road, Haidian District, Beijing, 100853, China. 3. Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. 4. USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Ave, Los Angeles, CA, 90033, USA. 5. Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA, 92868, USA. 6. Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA. 7. Haalthy Co., Ltd., Beijing, China. 8. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. 9. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan Nan Li, Chaoyang District, Beijing, 100021, China. Electronic address: wangyanyifu@163.com.
Abstract
OBJECTIVES: To describe the treatment patterns and outcomes of Chinese non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in real-world as EGFR ex20ins consist of a diverse group of mutations with limited information on the clinical outcome of these patients treated with chemotherapy or EGFR tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: Real-world treatment outcomes of Chinese NSCLC patients harboring EGFR ex20ins were retrospectively analyzed based on medical records at different institutions and detailed web-based patient questionnaires. RESULTS: Between March 17, 2018 and December 20, 2018, 165 advanced EGFR ex20ins NSCLC patients treated in 99 hospitals from 26 different regions in China were analyzed. Thirty-nine different molecular variants of EGFR ex20ins were identified with V769_D770insASV being the most common (23.0 %). Central nervous system (CNS) metastasis occurred in 23.0 % of patients at the time of baseline diagnosis. Median progression-free survival (PFS) was significantly longer in patients who received first-line platinum-based chemotherapy (6.4 m; 95 % CI: 5.7-7.1) than all-generation EGFR TKIs (2.9 m; 95 %CI: 1.5-4.3; P < 0.001) or 1st-generation EGFR TKIs (2.0 m; 95 %CI: 0.2-3.8; P < 0.001). Median PFS was numerically longer in patients who received second-line chemotherapy (4.0 m; 95 %CI: 3.2-4.8) than those received second-line EGFR TKIs (2.0 m; 95 %CI: 1.1-2.9; P = 0.342). Patients with CNS metastasis had numerically shorter median PFS than those without CNS metastasis when treated with 1st-line chemotherapy (3.6 m; 95 %CI: 0-8.0 vs. 6.5 m; 95 %CI: 4.9-8.1; P = 0.645) or 1st-line EGFR TKIs (2.0 m; 95 %CI: 0.8-3.2 vs. 2.9 m; 95 %CI: 2.1-3.7; P = 0.058). CONCLUSION: Chemotherapy is superior to current approved EGFR TKIs as 1st- or 2nd-line treatment of EGFR ex20ins mutations. CNS metastasis conferred numerically shorter PFS with chemotherapy or EGFR TKIs treatment. Targeted agent against EGFR ex20ins with CNS activity is urgently needed.
OBJECTIVES: To describe the treatment patterns and outcomes of Chinese non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in real-world as EGFR ex20ins consist of a diverse group of mutations with limited information on the clinical outcome of these patients treated with chemotherapy or EGFR tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: Real-world treatment outcomes of Chinese NSCLC patients harboring EGFR ex20ins were retrospectively analyzed based on medical records at different institutions and detailed web-based patient questionnaires. RESULTS: Between March 17, 2018 and December 20, 2018, 165 advanced EGFR ex20ins NSCLC patients treated in 99 hospitals from 26 different regions in China were analyzed. Thirty-nine different molecular variants of EGFR ex20ins were identified with V769_D770insASV being the most common (23.0 %). Central nervous system (CNS) metastasis occurred in 23.0 % of patients at the time of baseline diagnosis. Median progression-free survival (PFS) was significantly longer in patients who received first-line platinum-based chemotherapy (6.4 m; 95 % CI: 5.7-7.1) than all-generation EGFR TKIs (2.9 m; 95 %CI: 1.5-4.3; P < 0.001) or 1st-generation EGFR TKIs (2.0 m; 95 %CI: 0.2-3.8; P < 0.001). Median PFS was numerically longer in patients who received second-line chemotherapy (4.0 m; 95 %CI: 3.2-4.8) than those received second-line EGFR TKIs (2.0 m; 95 %CI: 1.1-2.9; P = 0.342). Patients with CNS metastasis had numerically shorter median PFS than those without CNS metastasis when treated with 1st-line chemotherapy (3.6 m; 95 %CI: 0-8.0 vs. 6.5 m; 95 %CI: 4.9-8.1; P = 0.645) or 1st-line EGFR TKIs (2.0 m; 95 %CI: 0.8-3.2 vs. 2.9 m; 95 %CI: 2.1-3.7; P = 0.058). CONCLUSION: Chemotherapy is superior to current approved EGFR TKIs as 1st- or 2nd-line treatment of EGFR ex20ins mutations. CNS metastasis conferred numerically shorter PFS with chemotherapy or EGFR TKIs treatment. Targeted agent against EGFR ex20ins with CNS activity is urgently needed.
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