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Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202)

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Frontiers of Medicine 2022年第5期16卷 766-772页

作者： Jianhua Shi Ying cheng Qiming Wang Kai Li Lin Wu Baohui Han Gongyan chen Jianxing He Jie Wang Haifeng Qin Xiaoling Li Department of Medical Oncology Linyi Cancer HospitalLinyi 276002China Department of Thoracic Medical Oncology Jilin Cancer HospitalChangchun 130012China Department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhou 450003China Department of Pulmonary Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Thoracic Medical Oncology The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University(Hunan Cancer Hospital)Changsha 410031China Department of Respiratory Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of Respiratory Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Thoracic Surgery The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Pulmonary Oncology The Fifth Medical Centre of Chinese PLA General HospitalBeijing 100039China Department of Medical Oncology Liaoning Cancer HospitalShenyang 110042China

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ≥ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gamma-glutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.

关键词： anlotinib chemotherapy short-term relapsed small-cell lung cancer

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A fully absorbable biomimetic polymeric micelle loaded with cisplatin as drug carrier for cancer therapy

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Regenerative Biomaterials 2018年第1期5卷 1-8页

作者： Weihua Zhuang Boxuan Ma gongyan Liu Xiaobing chen Yunbing Wang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China Department of Biomass Chemistry National Engineering Laboratory of Clean Technology of Leather ManufactureSichuan UniversityChengdu 610064China

cis-dichlorodiammineplatinum(II)(CDDP)-loaded polymeric micelles for cancer therapy have been developed to reduce the serious side effects of cisplatin CDDP.Herein,polymeric micelles incorporated with cisplatin are prepared based on the complexation between CDDP and hydrophilic poly(L-glutamic acid)-b-poly(2-methacryloyloxyethyl phosphorylcholine)(PLG-b-PMPC)diblock copolymers.These CDDP-loaded micelles possess an average size of 91nm with narrow distribution,providing remarkable stability in media containing proteins.The release of CDDP from the micelles is faster at pH 5.0 and pH 6.0 than that at pH 7.4 and in a sustained manner without initial burst release.In addition,there is almost no difference in cellular uptake between these CDDP-loaded micelles and free CDDP.Moreover,in vitro cytotoxicity test shows they possess high efficacy to kill 4T1 cells as compared with free drug.Thus,PLG-b-PMPC copolymer might be a promising carrier for CDDP incorporating in cancer therapy.

关键词： drug delivery cisplatin polymeric micelles cancer therapy

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Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment:A phase 2 clinical trial(BG01-1801)

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Cancer Pathogenesis and Therapy 2024年第2期2卷 103-111页

作者： Yuankai Shi Gongyan chen Yanqiu Zhao Jing Zhao Lin Lin Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted DrugsBeijing 100021China Department of Respiration Harbin Medical University Cancer HospitalHarbinHeilongjiang 150040China Respiratory Department of Internal Medicine Henan Provincial Cancer HospitalZhengzhouHenan 450003China Department of Pulmonary and Critcal Care Medicine Peking Union Medical College HospitaChinese Academy of Medical Sciences&Peking Union Medical College Beijing100021China

Background:Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer(NSCLC),but acquired resistance presents challenges.The aim of this open-label,multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone,a novel genetically engineered epothilone analog and microtubule-stabilizing agent,as a third-or later-line treatment for locally advanced ormetastatic NSCLC.Methods:Patients who had failed standard second-line treatment(including platinum-containing chemotherapy or targeted therapy)received utidelone(40 mg/m?via intravenous injection daily,day 1-5)every 21 days.The primary endpoint was the objective response rate(ORR).Secondary endpoints were the duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.Results:From March 12,2019 to January 18,2021,26 pretreated patients with locally advanced or metastatic NSCLC(100%of patients had received prior platinum and 65.4%patients had received prior taxane treatment)were enrolled(80.8%of patients had adenocarcinoma).At baseline,nine(34.6%)patients had received secondline treatment,10(38.5%)patients had received third-line treatment,and seven(26.9%)patients had received fourth-or later-line treatment.By the data cut-off date of August 10,2021,the median follow-up was 7.49 months(range,1.4-26.7 months).The ORR was 15.4%(95%confidence interval[CI],4.4%-34.9%)in the intention-totreat(ITT)cohort(N=26)and 19.0%(95%CI,5.4%-41.9%)in the per-protocol(PP)cohort(N=21).The disease control rate was 69.2%(95%CI,48.2%-85.7%)and 81.0%(95%CI,58.1%-94.6%)in the ITT and PP cohorts,respectively.The median DoR was 4.1 months(95%CI,3.1-5.1 months)in the ITT cohort.The median PFS was 4.37 months(95%CI,2.50-5.29 months)in the ITT cohort and 4.37 months(95%CI,2.50-9.76 months)in the PP cohort.The median OS was not reached,and the 12-month OS rate was 69%(95%CI,45.1%-84.1%).Grade 3/4 treatment-emergent adverse events occurred in 38.5%of patients,and the most common was

关键词： Utidelone Locally advanced or metastatic non-small-cell lung cancer Efficacy Platinum-and taxane-refractory

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Third-line or above anlotinib in relapsed and refractory small cell lung cancer patients with brain metastases:A post hoc analysis of ALTER1202,a randomized,double-blind phase 2 study

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Cancer Innovation 2023年第3期2卷 181-190页

作者： Ying cheng Qiming Wang Kai Li Jianhua Shi Baohui Han Lin Wu Gongyan chen Jianxing He Jie Wang Haifeng Qin Xiaoling Li Department of Thoracic Medical Oncology Jilin Cancer HospitalChangchunChina Department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouChina Department of Pulmonary Oncology Tianjin Medical University Cancer HospitalTianjinChina Department of Medical Oncology Linyi Cancer HospitalLinyiChina Department of Respiratory Medicine Shanghai Chest HospitalShanghai Jiaotong UniversityShanghaiChina Department of Thoracic Medical Oncology Hunan Cancer HospitalChangshaChina Department of Respiratory Medicine Harbin Medical University Cancer HospitalHarbinChina Department of Thoracic Surgery The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Thoracic Medical Oncology Cancer Hospital Chinese Academy of Medical SciencesBeijingChina Department of Pulmonary Oncology The Fifth Medical Centre of Chinese PLA General HospitalBeijingChina Department of Medical Oncology Liaoning Cancer Hospital and InstituteShenyangChina

Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM.Methods:This was a subgroup analysis of the ALTER1202 trial,which was a randomized,placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC.This study included patients with BM at baseline.The efficacy and safety outcomes included progression-free survival(PFS),overall survival(OS),central nervous system(CNS),objective response rate(ORR),CNS disease control rate(DCR),time to CNS progression,and adverse events(AEs).Results:Twenty-one and nine patients with BM were included in the anlotinib and placebo groups,respectively.The median PFS and OS were 3.8 months(95%confidence interval[CI]:1.8-6.1)and 6.1 months(95%CI:4.1-8.0)in the anlotinib group.Anlotinib was associated with a significant improvement in PFS(hazard ratio[HR]=0.15,95%CI:0.04-0.51,p=0.0005)and OS(HR=0.26,95%CI:0.09-0.73,p=0.0061)than placebo.Anlotinib significantly prolonged the time to CNS progression(p<0.0001).The anlotinib group had a higher CNS DCR than placebo(95.2%vs.22.2%,p=0.0001).The most common grade 3 or higher AEs were increased lipase(19.0%),hypertension(14.3%),and hyponatremia(14.3%)in the anlotinib group.Conclusions:Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM,significantly delaying CNS progression.

关键词： anlotinib angiogenesis inhibitors brain metastasis advanced small cell lung cancer safety

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Polyphenol based hybrid nano-aggregates modified collagen fibers of biological valve leaflets to achieve enhanced mechanical,anticoagulation and anti-calcification properties

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Journal of Leather Science and Engineering 2022年第1期4卷 394-408页

作者： Shufen Li Shiying Lang Zhiqian chen Jingruo chen Weihua Zhuang Yangrui Du Yawen Yao gongyan Liu Mao chen Laboratory of Heart Valve Disease West China HospitalSichuan University37 Guoxue AlleyChengdu 610041China The Key Laboratory of Leather Chemistry and Engineering of Ministry of Education College of Biomass Science and EngineeringSichuan UniversityChengdu 610065China University of California Davis 1 Shields AveDavisCA 95616USA Faculty of Science and Engineering Aachen-Maastricht Institute for Biobased Materials(AMIBM)Maastricht UniversityBrightlands Chemelot Campus6167 RD GeleenThe Netherlands Department of Cardiology West China HospitalSichuan University37 Guoxue AlleyChengdu 610041China Regenerative Medicine Research Center West China HospitalSichuan University37 Guoxue AlleyChengdu 610041China

Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPly-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPly-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.

关键词： Tannic acid Bioprosthetic heart valve Antibacterial and anti-calcification

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金融助力开创乡村振兴新征程

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中国金融 2021年第18期 9-11页

作者：陈共炎中国银河证券

在庆祝中国共产党成立100周年大会上,习近平总书记代表党和人民庄严宣告,经过全党全国各族人民持续奋斗,我们实现了第一个百年奋斗目标,在中华大地上全面建成了小康社会,历史性地解决了绝对贫困问题,正在意气风发向着全面建成社会主义... 详细信息

在庆祝中国共产党成立100周年大会上,习近平总书记代表党和人民庄严宣告,经过全党全国各族人民持续奋斗,我们实现了第一个百年奋斗目标,在中华大地上全面建成了小康社会,历史性地解决了绝对贫困问题,正在意气风发向着全面建成社会主义现代化强国的第二个百年奋斗目标迈进。

关键词：绝对贫困乡村振兴小康社会庄严宣告社会主义现代化强国全面建成金融助力新征程

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履职尽责决胜脱贫攻坚

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中国金融 2020年第18期 9-10页

作者：陈共炎中国银河证券股份有限公司

今年是决战脱贫攻坚、决胜全面小康收官之年。党的十八大以来,党中央把脱贫攻坚作为全面建成小康社会的底线任务和标志性指标,作出了一系列重大部署。金融系统紧紧围绕“精准扶贫、精准脱贫”基本方略,深化金融改革,优化金融环境,强化... 详细信息

今年是决战脱贫攻坚、决胜全面小康收官之年。党的十八大以来,党中央把脱贫攻坚作为全面建成小康社会的底线任务和标志性指标,作出了一系列重大部署。金融系统紧紧围绕“精准扶贫、精准脱贫”基本方略,深化金融改革,优化金融环境,强化金融服务,收获了许多决战脱贫攻坚的典型经验和优秀做法,为决胜全面小康提供了有力的金融支持和保证。当前,在新冠肺炎疫情防控常态化背景下,我们更要凝心聚力,迎难而上,以必胜信念高质量打赢脱贫攻坚战,确保如期全面建成小康社会。

关键词：脱贫攻坚精准扶贫精准脱贫典型经验金融服务疫情防控必胜信念党的十八大以来

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IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

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Chinese Journal of Cancer Research 2024年第2期36卷 103-113页

作者： Yi-Long Wu Shun Lu Gongyan chen Jianxing He Jifeng Feng Yiping Zhang Liyan Jiang Hongming Pan Jianhua Chang Jian Fang Amy Cai Lilian Bu Jane Shi Jinjing Xia Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai Lung Cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China Department of Thoracic Oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Medical Oncology Jiangsu Cancer HospitalNanjing 210009China Department of Medical Oncology Zhejiang Cancer HospitalHangzhou 330022China Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of Medical Oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China Department of Thoracic Oncology Beijing Cancer HospitalBeijing 100142China Product Development Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

关键词： Atezolizumab East Asia non-small cell lung cancer programmed death-ligand 1 inhibitors monoclonal antibody

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CTLA-4在肺癌中的研究进展

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现代肿瘤医学 2021年第2期29卷 348-352页

作者：李丽陈公琰哈尔滨医科大学附属肿瘤医院黑龙江哈尔滨150000

细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)是一种白细胞分化抗原,也是T细胞上的一种跨膜受体,目前针对CTLA-4在抑制T细胞免疫应答中所起作用的研究取得了一定的突破和成绩,与程序性死亡受体1(p... 详细信息

细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)是一种白细胞分化抗原,也是T细胞上的一种跨膜受体,目前针对CTLA-4在抑制T细胞免疫应答中所起作用的研究取得了一定的突破和成绩,与程序性死亡受体1(programmed death receptor-1,PD-1)共同打开了肿瘤治疗的新局面。通过对上述两个靶点的抑制,可以激活免疫系统,增强T细胞介导的免疫反应,从而增强患者的抗肿瘤能力,并且相应的免疫检查点抑制剂(例如抗CTLA-4单克隆抗体Ipilimumab)已用于黑色素瘤、肺癌等癌种的临床治疗。现就CTLA-4、抗CTLA-4单克隆抗体在肺癌中的作用机制及研究进展作一综述。

关键词： CTLA-4 肺癌抗CTLA-4单克隆抗体肺癌免疫治疗

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基于PD-1/PD-L1抑制剂的非小细胞肺癌免疫治疗预测标志物的研究进展

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现代肿瘤医学 2021年第10期29卷 1822-1825页

作者：王佳慧陈公琰哈尔滨医科大学附属肿瘤医院呼吸内科黑龙江哈尔滨150000

肺癌的发病率及死亡率均居世界首位,其中非小细胞肺癌约占所有肺癌类型的85%,传统放化疗的有效率十分有限,靶向治疗的耐药问题广泛存在。随着对肿瘤免疫逃逸机制的不断深入研究,以PD-1/PD-L1抑制剂为首的免疫治疗有望为患者带来新的曙... 详细信息

肺癌的发病率及死亡率均居世界首位,其中非小细胞肺癌约占所有肺癌类型的85%,传统放化疗的有效率十分有限,靶向治疗的耐药问题广泛存在。随着对肿瘤免疫逃逸机制的不断深入研究,以PD-1/PD-L1抑制剂为首的免疫治疗有望为患者带来新的曙光。但相关临床研究提示,非选择人群只有约20%可从中获益,故筛选优势人群迫在眉睫。本文将对目前非小细胞肺癌PD-1/PD-L1抑制剂免疫治疗预测标志物的研究进展作一综述,旨在帮助临床更好的选择非小细胞肺癌免疫治疗优势人群,使患者最大程度获益。

关键词：非小细胞肺癌免疫治疗 PD-1/PD-L1抑制剂标志物

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