Kaiyan Chen1, Xiaoqing Yu1,2, Haiyang Wang1,2, Zhiyu Huang1, Yanjun Xu1, Lei Gong1, Yun Fan3,4. 1. Department of Chemotherapy, Zhejiang Cancer Hospital, No.1 East Banshan Road, Gongshu District, Hangzhou, 310022, China. 2. Department of Oncology, The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, China. 3. Department of Chemotherapy, Zhejiang Cancer Hospital, No.1 East Banshan Road, Gongshu District, Hangzhou, 310022, China. fanyun@zjcc.org.cn. 4. Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology and Cancer Research Institute, Hangzhou, 310022, China. fanyun@zjcc.org.cn.
Abstract
PURPOSE: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. However, the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 L858R mutation) remains undetermined. METHODS: Seven hundred and fifty-five non-small cell lung cancer (NSCLC) patients with EGFR mutation analyses for TKI therapy were identified between October 2010 and December 2015 in East of China. And 66 patients bearing uncommon EGFR mutations were included to collect data from TKI response and prognosis. We categorised EGFR uncommon mutations as: sensitizing rare mutations (group 1: G719X, L861Q, S768I); Ex20 ins (group 2), or complex mutations (G719X + L861Q, G719X + S768I, 19 del + T790M, 19 del + L858R, L858R + S768I, and L858R + T790M; group 3). RESULTS: Of 66 patients given EGFR-TKI treatment, rare sensitive mutations, Ex20 ins, and complex mutations were identified in 37 (56.1%), 9 (13.6%), and 20 (33.3%) cases, respectively. TKI efficacy in patients harboring uncommon EGFR mutations exhibited a tumor response rate of 28.8% and a median progression-free survival (PFS) of 4.8 months. Additionally, patients with complex EGFR mutations had significantly longer PFS when compared with the remaining sensitizing rare mutations or Ex20 ins cases (8.6 vs. 4.1 vs. 3.1 months; p = 0.041). Importantly, complex EGFR mutations were independent predictors of increased overall survival (Hazard Ratios = 0.31; 95% confidence intervals: 0.11-0.90; p = 0.031). Among them, patients harboring Del-19 combined with L858R mutations showed a tendency to have higher response rate (RR) and improved PFS than those with other complex mutation patterns (RR: 66.7 vs. 14.3%, p = 0.021; PFS: 10.1 vs. 8.6 months, p = 0.232). CONCLUSIONS: Personalized treatment should be evolving in different types of uncommon EGFR mutations. Clinical benefit from EGFR-TKIs was higher in NSCLC patients with complex EGFR mutations than those with other uncommon EGFR mutation types.
PURPOSE:Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. However, the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 L858R mutation) remains undetermined. METHODS: Seven hundred and fifty-five non-small cell lung cancer (NSCLC) patients with EGFR mutation analyses for TKI therapy were identified between October 2010 and December 2015 in East of China. And 66 patients bearing uncommon EGFR mutations were included to collect data from TKI response and prognosis. We categorised EGFR uncommon mutations as: sensitizing rare mutations (group 1: G719X, L861Q, S768I); Ex20 ins (group 2), or complex mutations (G719X + L861Q, G719X + S768I, 19 del + T790M, 19 del + L858R, L858R + S768I, and L858R + T790M; group 3). RESULTS: Of 66 patients given EGFR-TKI treatment, rare sensitive mutations, Ex20 ins, and complex mutations were identified in 37 (56.1%), 9 (13.6%), and 20 (33.3%) cases, respectively. TKI efficacy in patients harboring uncommon EGFR mutations exhibited a tumor response rate of 28.8% and a median progression-free survival (PFS) of 4.8 months. Additionally, patients with complex EGFR mutations had significantly longer PFS when compared with the remaining sensitizing rare mutations or Ex20 ins cases (8.6 vs. 4.1 vs. 3.1 months; p = 0.041). Importantly, complex EGFR mutations were independent predictors of increased overall survival (Hazard Ratios = 0.31; 95% confidence intervals: 0.11-0.90; p = 0.031). Among them, patients harboring Del-19 combined with L858R mutations showed a tendency to have higher response rate (RR) and improved PFS than those with other complex mutation patterns (RR: 66.7 vs. 14.3%, p = 0.021; PFS: 10.1 vs. 8.6 months, p = 0.232). CONCLUSIONS: Personalized treatment should be evolving in different types of uncommon EGFR mutations. Clinical benefit from EGFR-TKIs was higher in NSCLCpatients with complex EGFR mutations than those with other uncommon EGFR mutation types.
Authors: Gregory J Riely; Joel W Neal; D Ross Camidge; Alexander I Spira; Zofia Piotrowska; Daniel B Costa; Anne S Tsao; Jyoti D Patel; Shirish M Gadgeel; Lyudmila Bazhenova; Viola W Zhu; Howard L West; Tarek Mekhail; Ryan D Gentzler; Danny Nguyen; Sylvie Vincent; Steven Zhang; Jianchang Lin; Veronica Bunn; Shu Jin; Shuanglian Li; Pasi A Jänne Journal: Cancer Discov Date: 2021-02-25 Impact factor: 39.397
Authors: Insu Kim; Jung Seop Eom; Eun Jung Jo; Jeongha Mok Ki Uk; Kwangha Lee; Ki Uk Kim; Hye-Kyung Park; Min Ki Lee; Mi-Hyun Kim Journal: Thorac Cancer Date: 2019-05-30 Impact factor: 3.500