Pemetrexed-based chemotherapy for non-small-cell lung cancer patients with EGFR exon 20 insertion mutation: a multicenter study

Chun-Wei Xu; Wen-Xian Wang; Dong Wang; Qi-Ming Wang; Xing-Xiang Pu; You-Cai Zhu; Jian-Hui Huang; Zong-Yang Yu; Zhao-Lei Cui; Xiao-Hui Chen; Jin-Luan Li; Yong Fang; Hong Wang; Wu Zhuang; Shi-Jie Lan; Xin Cai; Yin-Bin Zhang; Wen-Bin Gao; Li-Ping Wang; Ke-Lin She; Chuang-Zhou Rao; Yue-Fen Zhou; Mei-Yu Fang; Li-Yun Miao; Lei Lei; Tang-Feng Lv; Yong Song

doi:10.21037/tlcr-20-382

Pemetrexed-based chemotherapy for non-small-cell lung cancer patients with EGFR exon 20 insertion mutation: a multicenter study

Transl Lung Cancer Res. 2020 Oct;9(5):1853-1861. doi: 10.21037/tlcr-20-382.

Authors

Chun-Wei Xu¹, Wen-Xian Wang², Dong Wang¹, Qi-Ming Wang³, Xing-Xiang Pu⁴, You-Cai Zhu⁵, Jian-Hui Huang⁶, Zong-Yang Yu⁷, Zhao-Lei Cui⁸, Xiao-Hui Chen⁹, Jin-Luan Li¹⁰, Yong Fang¹¹, Hong Wang¹², Wu Zhuang¹³, Shi-Jie Lan¹⁴, Xin Cai¹⁵, Yin-Bin Zhang¹⁶, Wen-Bin Gao¹⁷, Li-Ping Wang¹⁸, Ke-Lin She¹⁹, Chuang-Zhou Rao²⁰, Yue-Fen Zhou⁶, Mei-Yu Fang², Li-Yun Miao²¹, Lei Lei², Tang-Feng Lv¹, Yong Song¹

Affiliations

¹ Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
² Department of Medical Oncology, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou China.
³ Department of Internal Medicine, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
⁴ Department of Medical Oncology, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
⁵ Department of Thoracic Disease Center, Zhejiang Rongjun Hospital, Jiaxing, China.
⁶ Department of Oncology, Lishui Municipal Central Hospital, Lishui, China.
⁷ Department of Medical Oncology, the 900th Hospital of the Joint Logistics Team (the Former Fuzhou General Hospital), Fujian Medical University, Fuzhou, China.
⁸ Department of Clinical Laboratory, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China.
⁹ Department of Thoracic Surgery, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China.
¹⁰ Department of Radiotherapy, Xiamen Cancer Hospital, the First Affiliated Hospital of Xiamen University, Xiamen, China.
¹¹ Department of Oncology, Sir Run Run Shaw Hospital, Hangzhou, China.
¹² Department of Lung Cancer, the Fifth Medical Center, General of PLA, Beijing, China.
¹³ Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.
¹⁴ Department of Oncology, the First Hospital of Jilin University, Changchun, China.
¹⁵ Department of Oncology, the First Affiliated Hospital of Dalian Medical University, Dalian, China.
¹⁶ Department of Oncology, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.
¹⁷ Department of Oncology, Shenzhen Luohu People's Hospital, Shenzhen Guangdong, China.
¹⁸ Department of Oncology, Baotou Cancer Hospital, Baotou, China.
¹⁹ Department of Thoracic Surgery, the Central Hospital of Shaoyang City, Shaoyang, China.
²⁰ Department of Radiation and Chemotherapy, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China.
²¹ Department of Respiratory Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

Abstract

Background: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied.

Methods: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins.

Results: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767_V769dupASV (33/119, 27.73%), S768_D770dupSVD (19/119, 15.97%), N771_H773dupNPH (11/119, 9.24%), A763_Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 vs. 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 vs. 19.6 months, P=0.0769). Patients harboring A767_V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P<0.05).

Conclusions: To the best of our knowledge, it is the largest cohort study of advanced NSCLC patients with EGFR ex20ins across China. Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins.

Keywords: Exon 20 insertion (ex20ins); chemotherapy; non-small-cell lung cancer (NSCLC); pemetrexed.