2017-wclc-阿帕替尼肺癌領域成果盤點

1、,,,,2017 WCLC,,阿帕替尼肺癌領域成果盤點,中央醫(yī)學事務系統(tǒng)2017年10月 上海,Lu Yao,,,,,2017年世界肺癌大會,,,,,,,第18屆IASLC/WCLC 日本 橫濱周彩存 教授 - 阿帕替尼多線治療失敗的晚期非鱗非小細胞肺癌的療效和安全性研究張曉春 教授 –阿帕替尼治療原發(fā)性肺空洞回顧性研究張曉春 教授 –阿帕替尼治療腫瘤肺轉(zhuǎn)移肺空洞回顧性研究劉雨桃 教授 -阿帕替尼治療二線及二

2、線后化療失敗小細胞肺癌患者的前瞻性研究 宋勇 教授-阿帕替尼挽救治療晚期NSCLC患者的研究吳志勇 教授 -阿帕替尼聯(lián)合替吉奧治療后線治療NSCLC患者的有效性研究史清明 教授 –阿帕替尼治療NSCLC二線后聯(lián)合S-1探索性研究趙瓊 教授 –影像組學對阿帕替尼治療NSCLC末線治療探索性研究的評估,Ahead-L305 研究總體設計,?研究性質(zhì)：單中心、單臂、II期臨床研究?研究者：上海市肺科醫(yī)院腫瘤內(nèi)科 周

3、彩存 教授?研究設計：,?,主要終點：ORR,?,次要終點：PFS、DCR、OS，安全性,,治療直至PD、 死亡或不可耐受毒性,,阿帕替尼500mg,,年齡≥18歲，男女不限 不適用于現(xiàn)有標準治療方案的 末線非鱗非小細胞肺癌ECOG PS 0-2肝腎及骨髓功能良好(n=40),,,,,死亡,,隨訪,,,,,40%的患者為四線--十二線,*無法評價：1例于用藥15日后失訪脫落，1例臨床進展,Ahead-L305 研究結果,

4、,,,,,,,,,,,,,,,,,,,,,,AE名稱（≥10%）,例數(shù)（%）（1-4級）,例數(shù)（%）（3-4級）,合計,31 (77.5),9 (22.5),血小板減少,5 (12.5),2 (5),高血壓 蛋白尿,7(17.5)10 (25),2 (5)1 (2.5),手足皮膚反應 口腔潰瘍 咽部潰瘍,11 (27.5)9 (22.5)1（2.5）,2 (5)01（2.5）,乏力 食欲下降,8 (20)

5、5 (12.5),00,,,?高血壓、蛋白尿、手足皮膚反應以及口腔黏膜潰瘍?nèi)匀皇亲畛Ｒ姷牟涣挤磻?常見的3級不良反應為高血壓、血小板減少和手足皮膚反應；,,,,,,導致劑量暫停的AE,例數(shù)（%）,合計血小板減少 手足皮膚反應 高血壓蛋白尿 總膽紅素升高 咯血,9（22.5）3（7.5）2（5）1（2.5）1（2.5）1（2.5）1（2.5）,劑量減量,7（17.5%）,Ahead-L305 研究

6、結果,,,,,數(shù)據(jù)截至2017年03月12日,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

7、,,,,,,,,,,,,,,,,18 個月,PD前服藥時長,PD后服藥時長,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,6線-SD3線-SD3線-SD5線-SD5線-SD6線-SD3線-PR3線-SD2線-SD4線-SD4線-SD3線-SD6線-PR4線-PR2線-SD3線-SD2線-PR4線-SD4線-PR3線-PR2線-SD12線-SD5線-S

8、D3線-PR5線-SD7線-PR6線-SD3線-PD3線-PD4線-PD2線-SD3線-PD3線-3線-PD2線-PD3線-PD3線-SD3線-SD5線-3線-PD,Ahead-L305 研究 用藥時長,Ahead-L305 研究 PD后繼續(xù)服藥病例情況,?38例已進展病人中有9例進展后仍繼續(xù)服藥；?9例進展后繼續(xù)服藥患者4人死亡，5人PD。29例進展后未繼續(xù)用藥的病人中14例已死亡。,,

9、,,,,,,,,,,,,,,,,4540,38,9,50,10,15,20,25,3530,40,總數(shù),進展,PD后繼續(xù)用藥,病 例 數(shù),,數(shù)據(jù)截至2017年3月12日,*總數(shù)40例，38例進展，2例失訪,,,,,,,,,,,,,,,I,他到皿且 exe白antì-tumor effects by selectìvely ìnhìbìtìng VEGFR-2 A s

10、ìngle-arm Phase 2 study of 姐姐nìb monotherapy ìn advanced non-squamous NSCLC patìents showed promìsìng response acrossmultìple therapy lìnes (P3.02C-025，WCLC 2016 Abs

11、tracts). Wereport the updated effìcacy and safety data，as well as the clìnìcal,benefrt of contìnuìng 旦旦到舊jQ beyond ìnìtìal progressìon.,I,。同,I,The prìmary endpo

12、6;nt: overall response rate (ORR),The secondary endpoìnts: progression-free survival (PFS)，overall,I,[ Death 1,U 山川，,n a u' u e t d d u,e,L X,U W O,n-k tu 幣 em 巴 M,E 『 3,cg 口,t o emw時,陽,"-m,d叫,

13、a r,e e ov- P3T d,Age主 18 ，Male & Female advanced non-squamo us NSCLC patientsheavily pretreatedECOG PS 0-2 (n=咽),Follow-up visit,After study discontìnuatìon， 到國監(jiān) monotherapy or combìned therapy w

14、as allowed for patients on disease progression at the dìscretìon of the ìnvestìgators and under the consent of patients.,|: 二1l1Î:W: .F.lf.t州時 a且且由,,,,,I!1ßWt>>lmm,..fiiji#l#J"(ll

15、lrmlll.in#&1!,i!tiØ*,ðil.j#,.,,il,,,",,,m,,,m,,,,!JjITlil!,,m,,,,.,,,,,,,,,,i.,,,,,,D,,.,,ij(,.Mjlm,,,il"I.]1,,.,,1,,J[.],，,,,,4,,',,,,,9,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Em6 3%and EmI t_,,,lll

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17、1titwml.,mu a on.,|布，【昨E叫,The cutoff date,duratlon 0 apa.t r,dosage of 477 0 :,IIì11íi,w .ijjmm '.l,i]r:w(.] (,m !l!líW,t;mmm'I' 1Ie]I i#ltilr:r[.];i,89I圃叫,,OCR were,21.1% and,re

18、spectively. The median,progression-free (PFS),li'1!l'!I'm'''''i1l9l'm wæJ were.,0,，,..,t!lm1!1iQ""1,8,'!,.i,，,t" n.;"IIHI,Ðm.,，.t 'I iU :t

19、!ß!m,"，,'b,1t,.. .,......m 12 ....a.. .I.;,Patients continued apatinib alone,or combined therapy after progression,陽一…l,p:U巴 ... ?.. 裝鞠曲,E,俑G叼rn司 副班曲t'lJIm!礎陽 ;:J,E,aRatini b+Oocetaxel 500 mg,

20、PR,13.11,Second progression,Apatinib250mgSO4.24 mosOeaApatinib500mgNE0.33 町10SOeath帕川川 盯 111叫m陽,th,,!,,刷刷,,…,,u,伽n,,,陽…a,,,…D川w,,,,陀………a,,由礎,,h,,,e川PR… 附陽………刷,e例…… 缸C,肌,eω叫,,斗d,,斗,,1,,,叫,,脅h…,,,川『川川咐唰i,川

21、刷lilI川,,I陽…,,,,,l,,EllIiOOlß陽rmTIjIill'EIjIi rnmaiTm Rmllijtilñlimñl.(.，,,...Wijl,,,liiIililijlSl,,ω,,mo…,叫川川川on川,,…,…,,n,,川,,,a,,,叫,,a,,削,,,,,,Erml 而,陽,,l協(xié)陽陽…,,,陽,,怡e,,,町陽,,m叫,,,rr..l,,ω,,,,,,叫a 叫,,

22、,rn11川,,叫叫抽刷刷州r m,,l怡,,I!ml mmmamρI .,,????,,'"陰仰 豆 stomatltls,,,,. 0 ""'m!m"ël,,,,,,,þJ'…j叫叫…,AEs induded Grade 3 HFSRβeD.lWlJ.Iàíl】 盯Bβ,CONCLUSIONS,This updated ana

23、lysis furlher confirmed the efficacy and safety of apa創(chuàng)nib for heavily treated advanced non-squamous NSCLC. Continuing agatinib monotherap y or combined therapy could bring clinicalbenefit.,,cω[.1J1I((;s叩 !I:Iníl叫,

24、,,? 1 ;t J ? J ? ? ? ? ，1.1 U 11 11 ，‘ .1 .',蛐…………-Fig2.Ka抖ar>-M酷1Cllrve of O...e:raU Su:M'Ia!,， .,M…_..撞·國-,Fgt.Kap an-Meier CUN!l! 01Progression-rre:e

25、SVrvi...a.!,,張曉春教授回顧性研究總體設計,研究題目：阿帕替尼治療原發(fā)性肺癌和其他實體瘤的回顧性研究,研究設計：非干預、單臂、登記性 研究單位： 青島大學附屬醫(yī)院 主要研究者： 張曉春 教授,2015-2017年,,,,分層因素：性別、年齡、病理分型、 分期、手術史、化療線數(shù)(一般因素）空洞、CEA 研究終點：評估空洞和CEA對于患者PFS的影響,張曉春教授回顧性研究總體進展,,,,原發(fā)肺癌二線后mPFS：10.09月

26、,,,無空洞,-,---,,有空洞,,,?原發(fā)性肺癌和肺轉(zhuǎn)移瘤患者使用阿帕替尼誘導產(chǎn)生空洞， 形成空洞的患者mPFS明顯高于無空洞組；?原發(fā)性肺癌二線后mPFS可達到10.09個月；,,,A Prospective Study of Apatinib in Advanced Small Cell Lung Cancer Patients Failed from Two or More Lines of Chemotherapy

27、阿帕替尼治療二線及二線后化療失敗小細胞肺癌患者的前瞻性研究,Authors:Yutao Liu; Xingsheng Hu; Shengyu Zhou; Peng Liu; Junling Li; Yan Wang; Xuezhi Hao; Yuankai Shi*Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Antican

28、cer Molecular Targeted Drugs,National Cancer Center/Cancer Hospital，Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing,100021，China,? 主要研究終點：無進展生存期（PFS）,,,,二線及二線后化療失敗的 小細胞肺癌患者(n=25),,治療直

29、至疾病進展 或不可耐受,,,,阿帕替尼500mg qd,劉雨桃教授 SCLC研究總體設計,劉雨桃教授 SCLC研究結果,? 2016年11月10日至2017年6月18日，共入組10例患者? 10例患者均可進行有效性評估，第一周期末首次療效評價：1例患者PR，8例患者SD，1例患者PD,,第一周期末療效評價患者靶病灶變化情況,劉雨桃教授 SCLC研究結果,? 截至2017年6月18日，4例患者進展出組，6例患者仍繼續(xù)治療? 不

30、良反應可管理可耐受，1例患者發(fā)生3級高血壓，1例患者發(fā)生3級蛋白尿,,,,Study on the Effect of Apatinib Salvage Treatment of Advanced Non-Small Cell Lung Cancer. 阿帕替尼挽救治療晚期NSCLC患者的研究,Authors:Z. Xu, Chunwei Xu, W. Wang, Q. Xu, Wu Zhuang, Z. Song, Y. Zhu,

31、 M. Shi, Gang Chen, T.F. Lv, Yong SongNanjing General Hospital of Nanjing Command, PLA., Nanjing/China,宋勇教授 NSCLC研究總體設計,,觀察二線或三線治療失敗的NSCLC患者72例,,疾病進展或 符合終止標準,,阿帕替尼750mg qd,,,,,,,宋勇教授 NSCLC研究結果,? 2014年3月至2016年3月，共觀察7

32、2例患者；? 72例患者可進行有效性評估，ORR=13.89%，DCR=83.33%，中位PFS=4.8? AE發(fā)生率=83.33%，3級及以上AE發(fā)生率=30.55%,個月,,,,Study on the effect of apatinib salvage treatment of advanced non-small cell lung cancerZhenwu Xu1, Chunwei Xu1, Wenxian Wan

33、g2, Qian Xu3, Wu Zhuang1, Zhengbo Song2, Youcai Zhu4, Mingwei Shi5, Gang Chen1, Meiyu Fang2, Tangfeng Lv6, Yong Song61Fujian Cancer Hospital, 2Zhejiang Cancer Hospital, 3Fujian Union Hospital Affiliated Fujian Medical U

34、niver 4Zhejiang Rongjun Hospital, 5Chinese Academy of Sciences Cancer Hospital 6Jinling Hospital, Nanjing University SchoolCorrespondence to:Meiyu Fang, M.D. & PhD. or Gang Chen, M.D. & PhD.,sity,of Medicine,

35、China,,For questions， please contact Gang Chen（naichengang@126.com）,Printed by,,,,2017 IASLC WCLCAbstract #8285,,,,,Introduction Nodefinitive chemotherapeutic,regimen has been established in patient

36、s with non-lung,small-cellcancer(NSCLC),who failed second- orthird-line,treatment. The study ofthisaimisto,investigate the effect of apatinib in advanced non-small cell lung cancer.,,,Methods7

37、2 patients with advanced non- small cell lung cancer treated in our hospital from March 2014 to March 2016 were selected and given oral apatinib (750mg, qd) to tumor progression, death or toxicity i

38、ntolerance so far. The,objectiveresponseratediseasecontrolrate,(ORR),(DCR),,progression free survival (PFS),,andtoxicsideeffects,were Single,observedandobserved.,factor analysis was used to c

39、ompare the relationship between the clinical features and PFS.,,,,,ResultsThe median PFS of the patients was 4.8 months (95%CI:4.7-5.0). The results of single factor analysis showed that there were no s

40、ignificant differences between different gender, age, PS score, histological type, drive gene mutation and metastasis foci, the number of metastasis, metastasis, treatment history, line number a

41、nd duration of treatment in patients with PFS (P>0.05). The ORR of this group was 13.89%, DCR was 83.33%. According to the clinical data of 72 patients in the treatment of patients with the clinical effica

42、cy of the waterfall plot, we can see that there are 54 cases of patients with lesions to reduce the diameter of tumor lesions as the effective treatment of the standard, there were 10 patients with

43、 of PR. There are various types of adverse events occurred in 60 patients, the incidence rate was 83.33%, including 22 cases (30.55%) for the aged III.,Conclusions,Apatinib is a effectiveand,safe treatment,

44、inadvanced non-small cell lung cancer, andcan be carried out more in-depth researchand application in clinic.,,宋勇教授 NSCLC研究結果,The Efficiency of Apatinib Plus S-1 as Laterline Chemotherapy for Advanced Non-smal

45、l-Cell Lung Cancer. 阿帕替尼聯(lián)合替吉奧后線治療NSCLC患者的有效性研究,Authors:Zhiyong Wu, Guanghai Dai, Jianyu Wu, Yanrong Wang PLA General Hospital, Beijing/China,吳志勇教授 NSCLC研究總體設計,,回顧性分析二線或三線化療失 敗的NSCLC患者15例,,疾病進展或 符合終止標準,,阿帕替尼250mg qd+替吉

46、奧 40/60mg bid d1-14（21天為1周期）,,,,,,mPFS=3個月,吳志勇教授 NSCLC研究結果,? 2016年3月30日至2017年6月1日，共納入15例患者，12例可評估；? 12例患者可進行有效性評估，ORR=50%，DCR=83%，中位PFS=3個月? 最常見AE為高血壓(41.6%，5/12)，口腔黏膜炎(50%，6/12)，手足綜合征(33%，4/12)，乏力(33%，4/12)? 主要的3

47、級或4級AE有高血壓（16.6%，2/12），口腔黏膜炎（8.3%，1/12）和乏力（8.3%，1/12）,,,,,,,DCR83%,,,,,,,,,,,吳志勇教授 NSCLC研究結果,f』 S統(tǒng),喃ω仰va系,何仙也 懺 務,VArA,事,;-,/ h、a學,兌mf c,"的川川U AU,醫(yī),，飛 e央,飛、J M,中,BackgroundThere is no standard treatment st

48、rategy for patients,with advanced non-small cell lung cancer (NSCLC),who experienced progression with three or more lines,of chemotherapy. Apatinib ，a new tyrosine kinase,inhibitor targeting vascular endo

49、thelial growth factor,receptor 2 (VEGFR-2)，has been shown confirming,antitumor activity and manageable toxicities in breastRECIST criteria，the disease control rate was 83%，,and gastric cancers. Clinical tria

50、ls of apatinib on non­ sma川 cell lung cancer show that progression-付ee survival is improved，but the objective response rate is still low. However， It remains to be explored whet her the combi

51、ned treatment of apatinib plus S1 could be furthe r e何ective on NSCLC.MethodsWe retrospectively assessed the efficacy and safety of apatinib plus S1 in patients with advanced NSCLC after the failure of secon

52、d or third-line chemotherapy. The study group comprised 15 patients who received oral apatinib，at a dose of 250 mg daily，and S1，at a dose of 40-60mg bid 01-14，repeat eve叩 3 weeks ，for progression after the failure

53、of second or third-line chemotherapy for advanced NSCLC. Treatme nt was continued until disease progression,ResultsBetween Mar 30，2016 and Jun 1，2017，15 patients,were enrolled. In 15 patients，the re were 12 patie

54、nts,available for efficacy and safety evaluation. 4/12,(33%) patients experienced dose reduction during,treatment. Followed up to Jun 20 ，2017 ，the median,during time of treatment was 3 months. According to

55、,10/12 (pa叫al response 50%，6/ 12 and stable disease 33%，4/12). The most frequent treatment-related adverse events were seconda叩 hype同ension (41.6%，,5/12)， oralmucositis(50%， 6/12)， hand-foot,syndrome (33%，4/12) a

56、nd 陽tigue (33%，4/12). Main grade 3 or 4 toxicities were hypertension (16.6%， 2門2)，oral mucositis (8.3%，1/12) and fatigue (8.3%， 1/12),Corresponding author:Guanghai Dai，E-mail: daigh301@Vip.sina.com; Presenting au仙

57、。r:Zhiyong Wu,ConclusionsA patinib plus S1 exhibits superior activity and,acceptable toxicity for the heavily pretreated patients,with advanced non-small cell lung cancer.,::1-'---'-' ' 111&#

58、39;1'1,…,-,Character-istics,N('‘},Pa，tlents enroles,15lZyears6Z3 70,Patl町、ts eYaluated,AgemedlanR割草eSEXMale,8(67),f量mal量 a恒3),ECOGPS。,旦旦旦,5(4Z)到25),No.of pr-evious CT I ines23咀Abbr@vla宦lon!,3(25)9f

59、7S),ECOG PS. Eastern CO。阻ratlve 0"曲Iocv Group,peñom回nces國tusCT. CMm otMraPY,A11information and materials contained on this poster are protected by copyright,.阿帕苔尼聯(lián)合苔吉奧治療后線治療非小細胞肺癌患者顯示出眾的高效性，且不良反應可接受,史清明教授

60、肺鱗癌 研究總體設計,?研究性質(zhì)：單臂、開放、多中心、探索性研究?研究者：安徽胸科醫(yī)院史清明教授?研究設計：阿帕替尼治療二線治療失敗晚期肺鱗癌,?,主要終點：PFS,,至少接受過一次兩藥含鉑方案 化療失敗的肺鱗癌患者，至少 具有一個可測量病灶（N=30）,,,,PD不可耐受毒性患者要求停藥,,阿帕替尼，250-500mg/天，連續(xù)服用； 替吉奧60 mg/m2/天，連續(xù)服14 天，休7 天,?,次要終點

61、：OS，DCR，ORR，QoL，安全性,,史清明教授肺鱗癌 研究總體進展,,? 入組16例：男：女=15:1；PS 1：2：3=9：6：1? ORR=6.25%，DCR=43.75%、PFS、OS不成熟? 主要的不良事件集中在高血壓、手足皮膚反應、蛋白尿、乏力、腹瀉? 僅有1例患者出現(xiàn)了三級腹瀉,? 已入選 2017 WCLC；,Therapeutic Response Assessment of Non–Small Cel

62、l Lung Cancer Patients Treated With Apatinib: A Radiomics Approach based on CT Texture Features影像組學法評估阿帕替尼治療NSCLC響應,Authors:Department of Thoracic Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang

63、 University, Hangzhou,Zhejiang Province, ChinaDepartment of Radiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, ChinaDepartment of Radiotherapy, The First

64、Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ZhejiangProvince, ChinaGeneral Electric Health Care, China,趙瓊教授 影像組學研究總體設計,? 影像組學（radiomics）是通過對CT、MRI、PET等醫(yī)學影像感興趣區(qū)域提取數(shù)百個定量，對這些特征進行篩選、分析，用于描述

65、腫瘤生物學特征和異質(zhì)性等信息的一種高通量定量分析方法。? 影像組學在非小細胞肺癌（NSCLC）的精準治療中具有較大潛在應用價值，可用于肺結節(jié)良、惡性 淋巴結轉(zhuǎn)移、腫瘤基因表型等生物學特性判定，以及腫瘤對治療的反應性、預后及放射性肺損傷的 預測，為個體化治療提供客觀依據(jù)。? 病例來源于作者單位參研的阿帕替尼治療NSCLC III期研究（NCT 02332512）。作者單位納入19例 患者。依據(jù)RECIST標準，這19例患者被歸

66、為響應者（CR、PR）和無響應者（SD、PD）。治療后， 提取CT影像特征，利用LASSO邏輯回歸建立模型以區(qū)分應答者和非應答者。,趙瓊教授 影像組學研究進展,,,? 共有108張CT圖；隨機選取75張作為內(nèi)部模型構建隊列，剩余33張作為獨立驗證隊列。Radiomics共提取384個CT特征；其中21個用于模型構建。ROC曲線下面積（AUC）為0.903。獨立驗證隊列 的AUC為0.714。,趙瓊教授 影像組學研究進展,? 本研究建