Frontiers in Oncology (Sep 2020)
Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma
- Long-Hua Guo,
- Ming-Feng Zhang,
- He-Long Zhang,
- Jian-Ying Zhou,
- Xiao-Hong Cai,
- Yu Long,
- Qi-Sen Guo,
- Nong Yang,
- Jun Zhao,
- Zhan-Hong Xie,
- Bo Jiang,
- Ying Zhu,
- Yun Fan,
- Cong-Ying Xie,
- Yi Hu,
- Yu Yao,
- Jun Jia,
- Xiao-Ling Li,
- Jiu-Wei Cui,
- Xi-Zhao Sui,
- Wen Lin,
- Ying Cheng,
- Hui-Juan Wang,
- Chang-Li Wang,
- Ming-Fang Zhao,
- Gui-Bin Qiao,
- Li-Jun Peng,
- Lin Yang,
- Gong-Yan Chen,
- Kai-Can Cai,
- Xin-Hua Xu,
- Liang-Ming Zhang,
- Guo-Sheng Feng,
- Jing-Min Zhou,
- Guo-Wu Wu,
- Xiao-Rong Dong,
- Li-Feng Wang,
- Hong-Mei Zhang,
- Ya-Jie Gao,
- Qiu-Ying Jiang,
- Shun-Dong Cang,
- Zhi-Xiong Yang,
- Xia Song,
- Xiao-Qing Liu,
- Bo Zhu,
- Feng-Xia Chen,
- Chun-Hong Hu,
- Xi Chen,
- Yi-Long Wu,
- Qing Zhou
Affiliations
- Long-Hua Guo
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-Sen University, Meizhou, China
- Ming-Feng Zhang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China
- He-Long Zhang
- Department of Oncology, The Second Affiliated Hospital of Air Force Military Medical University, Xi'an, China
- Jian-Ying Zhou
- Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Xiao-Hong Cai
- Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Yu Long
- Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Qi-Sen Guo
- Internal Medicine (Respiratory) of Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shangdong Academy of Medical Sciences, Shangdong Cancer Hospital and Institute, Jinan, China
- Nong Yang
- Lung Cancer and Gastrointestinal Unit, Department of Medical Oncology, Hunan Cancer Hospital/Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China
- Jun Zhao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China
- Zhan-Hong Xie
- Respiratory Medicine Department, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute for Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Bo Jiang
- 0Department of Cadre Medical Oncology, No.3 Hospital Affiliated to Kunming Medical College (Yunnan Tumor Hospital), Kunming, China
- Ying Zhu
- 0Department of Cadre Medical Oncology, No.3 Hospital Affiliated to Kunming Medical College (Yunnan Tumor Hospital), Kunming, China
- Yun Fan
- 1Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
- Cong-Ying Xie
- 2Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Yi Hu
- 3Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China
- Yu Yao
- 4Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Jun Jia
- 5Department of Oncology, Dongguan People's Hospital, Dongguan, China
- Xiao-Ling Li
- 6Department of Thoracic Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
- Jiu-Wei Cui
- 7Cancer Center, The First Hospital of Jilin University, Changchun, China
- Xi-Zhao Sui
- 8Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
- Wen Lin
- 9Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
- Ying Cheng
- 0Department of Medical Oncology, Jilin Provincial Cancer Hospital, Changchun, China
- Hui-Juan Wang
- 1Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou, China
- Chang-Li Wang
- 2Department of Lung Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
- Ming-Fang Zhao
- 3Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Gui-Bin Qiao
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China
- Li-Jun Peng
- 4Department of Thoracic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, China
- Lin Yang
- 5Department of Thoracic Surgery, Shenzhen People's Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, China
- Gong-Yan Chen
- 6Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
- Kai-Can Cai
- 7Department of Thoracic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, China
- Xin-Hua Xu
- 8Oncology Department, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, China
- Liang-Ming Zhang
- 9Department of Medical Oncology, Yantai Yuhuangding Hospital, Yantai, China
- Guo-Sheng Feng
- 0Chemotherapy Section One, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
- Jing-Min Zhou
- 1Department of Respiratory and Critical Care, Tianjin Chest Hospital, Tianjin, China
- Guo-Wu Wu
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-Sen University, Meizhou, China
- Xiao-Rong Dong
- 2Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Li-Feng Wang
- 3Oncology Department, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Hong-Mei Zhang
- 4Department of Clinical Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
- Ya-Jie Gao
- 5Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Qiu-Ying Jiang
- 6Department of Oncology, The Second Hospital Affiliated to Harbin Medical University, Harbin, China
- Shun-Dong Cang
- 7Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, China
- Zhi-Xiong Yang
- 8Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Xia Song
- 9Department of Respiratory Medicine, Shanxi Provincial Cancer Hospital, Taiyuan, China
- Xiao-Qing Liu
- 0Department of Pulmonary Oncology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
- Bo Zhu
- 1Institute of Cancer, Xinqiao Hospital, The Third Military Medical University, Chongqing, China
- Feng-Xia Chen
- 2Thoracic Surgery, Hainan General Hospital, Haikou, China
- Chun-Hong Hu
- 3Cancer Center, The Second Xiangya Hospital, Central South University, Changsha, China
- Xi Chen
- 4Department of Oncology, The 900th Hospital of the People's Liberation Army Joint Service Support Force, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- Yi-Long Wu
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China
- Qing Zhou
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China
- DOI
- https://doi.org/10.3389/fonc.2020.01568
- Journal volume & issue
-
Vol. 10
Abstract
Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy.Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed.Results: The median DOT was 9.1 months (95% CI: 8.5–9.8), and the median OS was 26.2 months (95% CI: 24.2–28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set.Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.
Keywords
