Cuimin Ding

China experts consensus on the diagnosis and treatment of advanced stage primary lung cancer (2016 version)

Yuankai SHI, Yan SUN, Jinming YU, Cuimin DING, Ziping WANG, Changli WANG, Dong WANG, Cunde WANG, Zheng WANG, Mengzhao WANG, Xiuyi ZHI, You LU, Jifeng FENG, Yunpeng LIU, Xiaoqing LIU, Wei LIU, Gang WU, Xiaomei LI, Kai LI, Enxiao LI, Wei LI, Gongyan CHEN, Zhengtang CHEN, Ping YU, Ning WU, Milu WU, Wenhua XIAO, Li ZHANG, Yiping ZHANG, Shucai ZHANG, Shujun YANG, Xia SONG, Dongmei LIN, Rongcheng LUO, Li SHAN, Caicun ZHOU, Zongmei ZHOU, Qiong ZHAO, Chengping HU, Yi HU, Qisen GUO, Jianhua CHANG, Cheng HUANG, Xuan ZENG, Baohui HAN, Xiaohong HAN, Bo JIA, Ying HAN and Yu HUANG 1Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 4Beijing Cancer Hospital, 9Peking Union Medical College Hospital, 10Beijing Xuanwu Hospital, Capital Medical University, 14The 307th Hospital of Chinese People’s Liberation Army, 16Chinese People’s Liberation Army General Hospital, 22Department of Imaging Diagnostic, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 24The First Affiliated Hospital of Chinese People’s Liberation ArmyGeneral Hospital, 26Beijing Chest Hospital, Capital Medical University, Beijing, 36Shanghai Chest Hospital, Shanghai Jiaotong University, 31Shanghai PulmonaryHospital, Tongji University, 34Cancer Hospital, FudanUniversitay, Shanghai, 2Shandong Province Cancer Hospital, Ji’nan, 3The Fourth Hospital of HebeiMedical University, Shijiazhuang, 5Tianjin Medical University Cancer Institute & Hospital, Tianjin, 6Daping Hospital, The Third Military Medical University, Chongqing, 20Xinqiao Hospital of The Third Military Medical University, Chongqing, 7Yunnan Province Cancer Hospital, Kunming, 11West China Hospital of Sichuan University, Chengdu, 21Sichuan Cancer Hospital, Chengdu, 12Jiangsu Cancer Hospital, Nanjing, 13The First Hospital of China Medical University, Shenyang, 15Huazhong University of Science and Technology Union Hospital, Wuhan, 17The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an, 18The First Hospital of Jilin University, Changchun, 19HarbinMedical University Cancer Hospital, Harbin, 23Qinghai University Affiliated Hospital, Xining, 25Zhejiang Cancer Hospital, Hangzhou, 32The First Affiliated Hospital, Zhejiang University, Hangzhou, 27Henan Province Cancer Hospital, Zhengzhou, 28Shanxi Province Cancer Hospital, Taiyuan, 29Nanfang Hospital, Nanfang Medical University, Guangzhou, 30Cancer Hospital of Xinjiang Medical University, Urumqi, 33Xiangya Hospital, Central South University, Changsha, and 35Fujian Cancer Hospital, Fuzhou, China

Detection of EGFR mutations in plasma circulating tumour DNA as a selection criterion for first-line gefitinib treatment in patients with advanced lung adenocarcinoma (BENEFIT): a phase 2, single-arm, multicentre clinical trial

BACKGROUND Detection of EGFR mutations in tumour tissue is the gold-standard approach to ascertain if a patient will benefit from treatment with an EGFR tyrosine kinase inhibitor. However, if tissue is scant, another strategy is to use circulating tumour DNA (ctDNA), but this method needs validation in clinical trials. We did a prospective clinical trial to assess ctDNA-based EGFR mutation detection as a selection criterion for patients with lung adenocarcinoma receiving gefitinib as first-line treatment. METHODS BENEFIT is a multicentre, single-arm, phase 2 clinical trial at 15 centres in China. Patients aged 18-75 years with stage IV metastatic lung adenocarcinoma and EGFR mutations detected in ctDNA were given oral gefitinib 250 mg once daily as first-line treatment. The primary endpoint was the proportion achieving an objective response. Secondary endpoints included median progression-free survival and safety. Next-generation sequencing (NGS) of a 168-gene panel was used for genetic analysis of baseline blood samples. The primary efficacy analysis was done by intention to treat in patients who had at least one post-baseline tumour assessment. The safety analysis was done in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02282267. FINDINGS Between Dec 25, 2014, and Jan 16, 2016, 426 patients were screened for the trial, of whom 188 with EGFR mutations in ctDNA were enrolled and received gefitinib. 183 patients had one or more post-baseline tumour assessment and were included in the primary efficacy analysis. Median follow-up was 14·5 months (IQR 12·2-16·5). At the time of data cutoff (Jan 31, 2017), 152 patients had progressive disease or had died. The proportion achieving an objective response was 72·1% (95% CI 65·0-78·5). Median progression-free survival was 9·5 months (95% CI 9·07-11·04). Of 167 patients with available blood samples, 147 (88%) showed clearance of EGFR mutations in ctDNA at week 8, and median progression-free survival was longer for these patients than for the 20 patients whose EGFR mutations persisted at week 8 (11·0 months [95% CI 9·43-12·85] vs 2·1 months [1·81-3·65]; hazard ratio [HR] 0·14, 95% CI 0·08-0·23; p<0·0001). From baseline NGS data in 179 patients, we identified three subgroups of patients: those with EGFR mutations only (n=58), those with mutations in EGFR and tumour-suppressor genes (n=97), and those with mutations in EGFR and oncogenes (n=24). Corresponding median progression-free survival in these subgroups was 13·2 months (95% CI 11·5-15·0), 9·3 months (7·6-11·0), and 4·7 months (1·9-9·3), respectively (EGFR mutations only vs mutations in EGFR and tumour-suppressor genes, HR 1·78, 95% CI 1·23-2·58; p=0·002; EGFR mutations only vs mutations in EGFR and oncogenes, 2·66, 1·58-4·49; p=0·0003). The most common grade 3 or 4 adverse events were hepatic function abnormalities (n=24). Serious adverse events were reported in 17 (9%) patients. No unexpected safety events for gefitinib were recorded. INTERPRETATION Detection of EGFR mutations in ctDNA is an effective method to identify patients who might benefit from first-line gefitinib treatment. Further analyses of dynamic alterations of EGFR mutations and accompanying gene aberrances could predict resistance to gefitinib. FUNDING Guangdong Association of Clinical Trials, AstraZeneca, National Natural Sciences Foundation Key Programme, and National Key Research and Development Programme of China.

China experts consensus on icotinib for non-small cell lung cancer treatment (2015 version)

According to Chinese Cancer Registry Annual Report in 2011, the incidence rate of lung cancer was 48.32/100,000 and the mortality rate was 39.27/100,000 in China in 2011, being the highest among all cancers (1). Most patients with nonsmall cell lung cancer (NSCLC) which accounts for 85% of all lung cancers have entered the advanced stage at the first visit to hospital and thus missed the opportunity for surgery. As the main treatment for advanced NSCLC, chemotherapy has reached a plateau in its efficacy and has been restricted in clinical application due to adverse reactions. In recent years, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), thanks to their definite efficacy, mild adverse reaction and convenience for oral use, have broken the bottleneck of traditional chemotherapeutic drugs and become an essential treatment for advanced NSCLC.

China experts consensus on icotinib for non-small cell lung cancer treatment (2015 version).

According to Chinese Cancer Registry Annual Report in 2011, the incidence rate of lung cancer was 48.32/100,000 and the mortality rate was 39.27/100,000 in China in 2011, being the highest among all cancers (1). Most patients with non-small cell lung cancer (NSCLC) which accounts for 85% of all lung cancers have entered the advanced stage at the first visit to hospital and thus missed the opportunity for surgery. As the main treatment for advanced NSCLC, chemotherapy has reached a plateau in its efficacy and has been restricted in clinical application due to adverse reactions. In recent years, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), thanks to their definite efficacy, mild adverse reaction and convenience for oral use, have broken the bottleneck of traditional chemotherapeutic drugs and become an essential treatment for advanced NSCLC.

Establishment of a prospective multicenter cohort for advanced non-small cell lung cancer in China (CAPTRA-Lung study): CAPTRA-Lung study

The CAPTRA‐Lung study (NCT03334864) is a prospective observational study that will capture real‐world data of patients with advanced or metastatic non‐small cell lung cancer (NSCLC) across China. The study aims to complement the results from current therapeutic regimens to improve the standard of diagnosis and treatment, evaluate the effectiveness and safety of systemic therapy, and determine the factors influencing the outcomes and responses to treatment. From January 2018 to December 2023, eligible patients with advanced or metastatic NSCLC who are receiving treatment and participating in follow‐up at 16 institutions in China, will be enrolled. The demographic, clinical, laboratory, and treatment characteristics and responses to treatment will be recorded in a case report form and transcribed into an electronic data capture system. Overall survival, progression‐free survival, overall response rate, and incidence of adverse events will be calculated from the time of initial enrolment until progression evaluated by physicians, last contact, date of death, or analysis cutoff date, respectively. Based on the disease characteristics and treatment strategies, four sub‐cohorts will also be established. This study cohort could serve as a pool of patients with advanced or metastatic NSCLC to support further research.