Yuankai Shi

Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial.

The purpose of this study was to assess the efficacy, safety, and pharmacokinetics of cisplatin‐based chemotherapy plus cetuximab as first‐line treatment in Chinese and Korean patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).

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

Efficacy of erlotinib in previously treated patients with advanced non-small cell lung cancer: Analysis of the Chinese subpopulation in the TRUST study

OBJECTIVEnThis study is to analyze the data of Chinese subpopulation in the Tarceva Lung Cancer Survival Treatment Study (TRUST-China) which was a global Phase IV study designed to provide erlotinib to previously treated patients with Stage IIIB/IV non-small cell lung cancer.nnnMETHODSnPatients with pathologically confirmed, unresectable Stage IIIB/IV non-small cell lung cancer who were previously failed on or unsuitable for chemotherapy or radiotherapy were given erlotinib (150 mg/day, oral) until disease progression, intolerable toxicity or death. Efficacy and toxicity of the agent were evaluated.nnnRESULTSnIn total, 519 patients Chinese patients were analyzed. The TRUST-China had similar baseline characteristics to TRUST-Global except the greater percentage of adenocarcinoma and non-smoker cases. The response rate and disease control rate were 24.7 and 75.3%, respectively. Median progression-free survival and overall survival were 6.4 and 15.4 months in the general Chinese population in the TRUST, and 10.2 and 18.9 months in non-smokers with adenocarcinoma (n = 254). Median progression-free survival and overall survival were significantly longer in non-smokers with adenocarcinoma than those in other groups (P ≤ 0.0001 and P ≤ 0.0001, respectively). Eastern Cooperative Oncology Group Performance Status (≥ 2 vs. ≤ 1, hazard ratio = 1.746, P < 0.0001) and histology (squamous cell carcinoma vs. adenocarcinoma, hazard ratio = 1.595, P = 0.0008) were independent risk factors that affected survival according to Cox regression multivariate analysis.nnnCONCLUSIONSnWe confirmed the efficacy and safety of erlotinib in Chinese patients. Non-smoking patients with adenocarcinoma histology had the best clinical benefits. (NCT00949910).

Application of Single-Molecule Amplification and Resequencing Technology for Broad Surveillance of Plasma Mutations in Patients with Advanced Lung Adenocarcinoma

Liquid biopsy to access the circulating tumor DNA is a promising surrogate for invasive tumor genotyping. We designed a multiplex assay based on circulating single-molecule amplification and resequencing technology (cSMART) to simultaneously detect and quantitate hot spot EGFR, KRAS, BRAF, ERBB2, and ALK plasma DNA variants in 103 patients with advanced lung adenocarcinoma. In validation studies using an analytical mutation standard, the sensitivity of the assay for EGFR mutation detection was at least 0.1% and specificity was 100%. The diagnostic detection sensitivity was one mutant molecule per 2 mL of plasma. The most frequently detected plasma mutations were EGFR variants L858R (21.4%), exon 19 deletions (19.4%), T790M (9.7%), and KRAS G12X variants (9.7%). Rarer were BRAF V600X (1.95%) and ERBB2 exon 20 (0.97%) variants. In single samples, four novel EGFR exon 19 deletions, one KIF5B-ALK, and two EML4-ALK variants were also detected. From comparisons of 103 matched plasma and tumor specimen genotypes, 75 (72.8%) were concordant, 9 (8.8%) were partially concordant, and 19 (18.4%) were discordant. Overall, the combined positive and negative concordance rate for detection of each oncogenic variant exceeded 90%. On the basis of these findings, we propose that cSMART displays the diagnostic hallmarks of a comprehensive plasma genotyping assay, with potential application for precisely monitoring changes in plasma mutation levels in response to targeted drug therapy.

Efficacy and safety of third-line treatment with anlotinib in patients with refractory advanced non-small-cell lung cancer (ALTER-0303): a randomised, double-blind, placebo-controlled phase 3 study

Abstract Background Anlotinib hydrochloride, an oral tyrosine kinase inhibitor targeting VEGFR, FGFR, PDGFR, and c-kit, showed promising efficacy in a phase 2 study. Here, we evaluated the efficacy and safety of anlotinib as third-line treatment for advanced non-small-cell lung cancer. Methods We did a randomised, double-blind, placebo-controlled phase 3 trial (ALTER-0303) at 31 sites. Eligible patients with stage 3B/4 non-small-cell lung cancer who progressed after at least two lines of previous therapies were randomly assigned (2:1) to receive anlotinib (12 mg once a day from day 1 to 14 of a 21-day cycle) or placebo until progression or intolerable toxicity. Enrolled patients harbouring EGFR or ALK mutations must have failed in previous match-targeted therapies. The primary endpoint was overall survival. This trial is registered with ClinicalTrials, number NCT02388919. Findings Between February, 2015, and August, 2016, we randomly assigned 437 patients. The baseline characteristics of the anlotinib group (n=294) and placebo group (n=143) were well balanced in age, gender, ECOG performance status, and gene status. With 292 overall survival events (67%), a significant improvement in overall survival was observed in the anlotinib group compared with the placebo group (hazard ratio 0·68, 95% CI 0·54–0·87 p=0·0018), according to investigator-assessed results (table). Interpretation The ALTER-0303 trial met its primary endpoint; anlotinib significantly improved overall survival in advanced non-small-cell lung cancer with a manageable safety profile. The results strongly suggest that anlotinib should be considered as a candidate for the third-line treatment or beyond in advanced non-small-cell lung cancer. Funding Chia-tai Tianqing Pharmaceutical Co Ltd.

The efficacy and safety of icotinib in patients with advanced non-small cell lung cancer previously treated with chemotherapy: A single-arm, multi-center, prospective study

Background Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Methods Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. Results From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9–6.6 m) and 5.4 months (95%CI 3.1–7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). Conclusions In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. Trial Registration ClinicalTrials.gov NCT02486354

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.

Expert Consensus on the Diagnosis and Treatment of Bone Metastasis in Lung Cancer (2014 version)

Expert Consensus on the Diagnosis and Treatment of Bone Metastasis in Lung Cancer (2014 version) Yan SUN, Zhongzhen GUAN, Meilin LIAO, Xin YU, Changli WANG, Jie WANG, Xiaohui NIU, Yuankai SHI, Xiuyi ZHI, Yunpeng LIU, Mengzhong LIU, Yiping ZHANG, Yue YANG, Jingnan SHEN, Gongyan CHEN, Qinghua ZHOU, Caicun ZHOU, Qisen GUO, Lili TANG, Jianchun DUAN , Jun LIANG, Yingjian ZHANG, Ying CHENG 22 Cancer Hospital, Chinese Aacademy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; SunYat-Sen University Cancer Center,Guangzhou 510060, China; Shanghai Chest Hospital, Shanghai, 200030, China; Department of psychiatry, Peking University Sixth Hospital, Beijing 100191, China; Department of Lung Cancer Surgery, Tianjin Cancer Hospital, Tianjin 300060, China; Department of oracic Medical Oncology, Beijing Cancer Hospital, Peking University, Beijing 100142, China; Department of Orthopedic Oncology Surgery, Beijing Jishuitan Hospital, Beijing 100035, China; Department of Medical Oncology, Cancer Hospital, Chinese Aacademy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Department of oracic Surgery, Beijing Lung Cancer Center, Beijing Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Departmentof Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China; Department of Radiotherapy, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China; Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou 310022, China; Department of oracic Surgery, Beijing Cancer Hospital, Peking University, Beijing 100142, China; Department of Orthopedic Oncology Surgery, the First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, China; Department of Medical Oncology, Haerbin Medical University Cancer Hospital, Haerbin 150081, China; Department of oracic Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Departmentof Medical Oncology, Shanghai Pulmonary Hospital, Shanghai 200433, China; Department of Medical Oncology, Shandong Province cancer Hospital, Jinan 250117, China; Department of rehabilitation, Beijing Cancer Hospital, Peking University, Beijing 100142, China; Department of Medical Oncology, the A ated Hospital of Qingdao University, Qingdao 266003, China; Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Medical Oncology, Jilin Cancer Hospital, Changchun 130012, China DOI: 10.3779/j.issn.1009-3419.2014.02.01

Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non–Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial

Importance Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. A phase 2 trial showed anlotinib to improve progression-free survival with a potential benefit of overall survival, leading to the phase 3 trial to confirm the drug’s efficacy in advanced non–small cell lung cancer (NSCLC). Objective To investigate the efficacy of anlotinib on overall survival of patients with advanced NSCLC progressing after second-line or further treatment. Design, Setting, and Participants The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical trial designed to evaluate the efficacy and safety of anlotinib in patients with advanced NSCLC. Patients from 31 grade-A tertiary hospitals in China were enrolled between March 1, 2015, and August 31, 2016. Those aged 18 to 75 years who had histologically or cytologically confirmed NSCLC were eligible (nu2009=u2009606), and those who had centrally located squamous cell carcinoma with cavitary features or brain metastases that were uncontrolled or controlled for less than 2 months were excluded. Patients (nu2009=u2009440) were randomly assigned in a 2-to-1 ratio to receive either 12 mg/d of anlotinib or a matched placebo. All cases were treated with study drugs at least once in accordance with the intention-to-treat principle. Main Outcomes and Measures The primary end point was overall survival. The secondary end points were progression-free survival, objective response rate, disease control rate, quality of life, and safety. Results In total, 439 patients were randomized, 296 to the anlotinib group (106 [36.1%] were female and 188 [64.0%] were male, with a mean [SD] age of 57.9 [9.1] years) and 143 to the placebo group (46 [32.2%] were female and 97 [67.8%] were male, with a mean [SD] age of 56.8 [9.1] years). Overall survival was significantly longer in the anlotinib group (median, 9.6 months; 95% CI, 8.2-10.6) than the placebo group (median, 6.3 months; 95% CI, 5.0-8.1), with a hazard ratio (HR) of 0.68 (95% CI, 0.54-0.87; Pu2009=u2009.002). A substantial increase in progression-free survival was noted in the anlotinib group compared with the placebo group (median, 5.4 months [95% CI, 4.4-5.6] vs 1.4 months [95% CI, 1.1-1.5]; HR, 0.25 [95% CI, 0.19-0.31]; Pu2009<u2009.001). Considerable improvement in objective response rate and disease control rate was observed in the anlotinib group over the placebo group. The most common grade 3 or higher adverse events in the anlotinib arm were hypertension and hyponatremia. Conclusions and Relevance Among the Chinese patients in this trial, anlotinib appears to lead to prolonged overall survival and progression-free survival. This finding suggests that anlotinib is well tolerated and is a potential third-line or further therapy for patients with advanced NSCLC. Trial Registration ClinicalTrials.gov identifier: NCT02388919