A multicenter-retrospective study of non-small-cell lung carcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations: different subtypes of EGFR exon 19 deletion-insertions exhibit the clinical characteristics and prognosis of non-small cell lung carcinoma

Ying Chen; Jinhe Xu; Lei Zhang; Yingfang Song; Wen Wen; Jun Lu; Zhongquan Zhao; Wencui Kong; Wei Liu; Aiping Guo; Mariacarmela Santarpia; Tadaaki Yamada; Xiuyu Cai; Zongyang Yu

doi:10.21037/tlcr-22-48

A multicenter-retrospective study of non-small-cell lung carcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations: different subtypes of EGFR exon 19 deletion-insertions exhibit the clinical characteristics and prognosis of non-small cell lung carcinoma

Transl Lung Cancer Res. 2022 Feb;11(2):238-249. doi: 10.21037/tlcr-22-48.

Authors

Ying Chen^#¹, Jinhe Xu^#², Lei Zhang¹, Yingfang Song¹, Wen Wen¹, Jun Lu³, Zhongquan Zhao¹, Wencui Kong¹, Wei Liu¹, Aiping Guo⁴, Mariacarmela Santarpia⁵, Tadaaki Yamada⁶, Xiuyu Cai⁷, Zongyang Yu¹

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Fuzhou General Hospital of Fujian Medical University, Dongfang Hospital of Xiamen University, The 900th Hospital of the Joint Logistic Support Force, PLA, Fuzhou, China.
² Department of Respiratory and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China.
³ Laboratory of Basic Medicine, Fuzong Clinical College (900th Hospital of the Joint Logistics Team), Fujian Medical University, Fuzhou, China.
⁴ Department of Medical Oncology, Dongfang Hospital of Xiamen University, Fuzhou General Hospital of Fujian Medical University, The 900th Hospital of the Joint Logistic Support Force, PLA, Fuzhou, China.
⁵ Medical Oncology Unit, Department of Human Patology "G. Barresi", University of Messina, Messina, Italy.
⁶ Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁷ Department of VIP Inpatient, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

^# Contributed equally.

Abstract

Background: The aim of this study was to investigate the clinical features, immunohistochemistry (IHC), compound mutation, and prognosis of patients with non-small cell lung cancer (NSCLC) harboring exon 19 deletion-insertion mutations.

Methods: This retrospective analysis included 4,666 NSCLC patients harboring epidermal growth factor receptor (EGFR) mutations in a multi-center study from January 2017 to December 2020, and 69 patients with EGFR exon 19 deletion-insertions were taken to account. Next-generation sequencing (NGS) was used to detect the subtype of EGFR exon 19 deletion-insertions. These mutations were correlated with clinical features, immunophenotype and molecular characteristics of tumors and outcomes of patients.

Results: Sixty-nine patients with EGFR exon 19 deletion-insertions were analyzed in this study, comprising 24 cases (34.8%) with L747_P753delinsS, 9 cases (13.1%) with L747_A750delinsP, both 5 cases (7.2%) in E746_A750delinsQP, E746_S752delinsV and both 4 cases (5.8%) in E746_T751delinsA and L747_T751delinsP. Twenty-nine males (42%) and 40 females (58%), with a median age of 59.7 years; 12 (21.7%) participants were smokers and 54 (78.3%) were nonsmokers. The compound mutations were tumor protein 53 (TP53) (45.83%), phosphoinositide-3-kinase (PIK3CA) (11.59%), and almost 16.67% in retinoblastoma 1 (RB1), melanocyte stimulating hormone (MSH), and myelocytomatosis (MYC). The best overall response was complete response (CR) in 47.8% of patients, partial response (PR) in 33.3% and stable disease (SD) in 13.1% of patients. Correlation between immunoreactivity of Napsin A, thyroid transcription factor (TTF), cytokeratin (CK7), surfactant proteins B (SPB), and the subtypes of EGFR exon 19 deletion-insertion was significantly statistically different (P<0.05). The disease control rate (DCR) was 29%. The median progression-free survival (mPFS) and 95% confidence interval (CI) of exon 19 deletion-insertion subtypes were 14.821 (9.917 to 19.726) months for L747_P753delinsS, 23.500 (15.877 to 31.123) months for L747_A750delinsP, 26.667 (11.731 to 41.603) months for L747_T751delinsP, and 11.713 (7.786 to 15.639) months for the others. Patients receiving treatment with 3rd generation tyrosine kinase inhibitors (TKI) had the shortest progression-free survival (PFS) (median: 7.179, 95% CI: 3.969-10.388).

Conclusions: The subtypes of exon 19 deletion-insertion exhibited different clinical characteristics compared with other common mutations. Our finding argued in favor of analyzing the correlation between immunoreactivity and the subtypes of EGFR exon 19 deletion-insertion. The EGFR exon 19 deletion-insertion mutations exhibited limited sensitivity to 3rd generation TKI. Moreover, in light of therapeutic effect for the subtype, L747_T751delinsP achieved longer PFS.

Keywords: EGFR exon 19 deletion-insertion; next-generation sequencing (NGS); non-small cell lung cancer (NSCLC).