Hai-Yan Tu1, E-E Ke2, Jin-Ji Yang2, Yue-Li Sun2, Hong-Hong Yan2, Ming-Ying Zheng2, Xiao-Yan Bai2, Zhen Wang2, Jian Su2, Zhi-Hong Chen2, Xu-Chao Zhang2, Zhong-Yi Dong3, Si-Pei Wu2, Ben-Yuan Jiang2, Hua-Jun Chen2, Bin-Chao Wang2, Chong-Rui Xu2, Qing Zhou2, Ping Mei4, Dong-Lan Luo4, Wen-Zhao Zhong2, Xue-Ning Yang2, Yi-Long Wu5. 1. Southern Medical University, Guangzhou, 510080, People's Republic of China; Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China. 2. Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China. 3. Southern Medical University, Guangzhou, 510080, People's Republic of China. 4. Department of Pathology, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China. 5. Southern Medical University, Guangzhou, 510080, People's Republic of China; Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China. Electronic address: syylwu@live.cn.
Abstract
INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations are a heterogeneous group exhibiting differential responses to EGFR inhibitors. This retrospective study reviews the prevalence of uncommon EGFR mutations in a Chinese NSCLC cohort and the clinical characteristics and efficacy of EGFR tyrosine kinase inhibitors (TKIs) associated with these patients. MATERIALS AND METHODS: A total of 5363 lung cancer patients were screened and underwent EGFR genotyping at the Guangdong Lung Cancer Institute. Of those with uncommon EGFR mutations, the clinical characteristics and responses to EGFR-TKIs were reviewed retrospectively. RESULTS: Uncommon EGFR mutations were observed in 218 patients, comprising 11.9% of all patients with documented EGFR mutations. More smokers (30.7% vs. 24.3%, P=0.039) and males (54.1% vs. 44.4%, P=0.007) were among the patients with uncommon mutations compared with common mutations. The most frequent uncommon mutations were exon 20 insertions (30.7%, n=67), followed by G719X mutations (21.1%, n=46) and compound L858R mutations (17.0%, n=37). Favorable efficacy was observed in patients harboring compound L858R or G719X mutations, with a median progression-free survival (PFS) of 15.2 (95% CI: 8.7-21.7) or 11.6 (95% CI: 3.6-19.6) months, respectively. The median PFS of those with the T790M mutation or an exon 20 insertion was 1.0 (95% CI: 0.0-2.2) and 3.0 (95% CI: 1.3-4.7) months, respectively. CONCLUSION: This study reviewed the prevalence of uncommon EGFR mutations and their sensitivity to EGFR-TKIs. Favorable responses were observed in patients with G719X and compound L858R mutations, indicating that they may benefit from EGFR-TKIs as a first-line therapy.
INTRODUCTION:Patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations are a heterogeneous group exhibiting differential responses to EGFR inhibitors. This retrospective study reviews the prevalence of uncommon EGFR mutations in a Chinese NSCLC cohort and the clinical characteristics and efficacy of EGFR tyrosine kinase inhibitors (TKIs) associated with these patients. MATERIALS AND METHODS: A total of 5363 lung cancerpatients were screened and underwent EGFR genotyping at the Guangdong Lung Cancer Institute. Of those with uncommon EGFR mutations, the clinical characteristics and responses to EGFR-TKIs were reviewed retrospectively. RESULTS: Uncommon EGFR mutations were observed in 218 patients, comprising 11.9% of all patients with documented EGFR mutations. More smokers (30.7% vs. 24.3%, P=0.039) and males (54.1% vs. 44.4%, P=0.007) were among the patients with uncommon mutations compared with common mutations. The most frequent uncommon mutations were exon 20 insertions (30.7%, n=67), followed by G719X mutations (21.1%, n=46) and compound L858R mutations (17.0%, n=37). Favorable efficacy was observed in patients harboring compound L858R or G719X mutations, with a median progression-free survival (PFS) of 15.2 (95% CI: 8.7-21.7) or 11.6 (95% CI: 3.6-19.6) months, respectively. The median PFS of those with the T790M mutation or an exon 20 insertion was 1.0 (95% CI: 0.0-2.2) and 3.0 (95% CI: 1.3-4.7) months, respectively. CONCLUSION: This study reviewed the prevalence of uncommon EGFR mutations and their sensitivity to EGFR-TKIs. Favorable responses were observed in patients with G719X and compound L858R mutations, indicating that they may benefit from EGFR-TKIs as a first-line therapy.
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