仑伐替尼研究解读

ASCO-GI

2019关于仑伐替尼的报道Oral

presentation-探究REFLECT研究中OR状态与OS的关系

PosterNo.316-探讨REFLECT研究中，基于患者基线体重选择仑伐替尼起始剂量对有效性和安全性的影响Poster

No.317-仑伐替尼用于肝细胞癌患者的总生存和不良事件相关性的分析Poster

No.371-REFLECT研究事后分析结果公布REFLECT研究设计全球多中心,随机、开放性、III期非劣效性研究BCLC:巴塞罗那临床肝癌；ECOGPS:东部合作肿瘤组的性能状态；mRECIST:修订的实体瘤反应评价标准；ORR:客观回应率；OS:总存活期；PFS:无进展存活期；:实体肿瘤反应评价标准；TTP:疾病进展时间；TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316分层依据地区（亚太地区或西方国家）门静脉浸润和/或肝外扩散（是或否）ECOG-PS（0或1分）体重（<60kg或≥60kg）乐卫玛®（N

=

478

）12

mg（体重≥60

kg）或8

mg（体重<60

kg）每天一次索拉非尼（n=476

）400

mg每日两次不可切除的肝细胞癌患者（N

=

954）未接受过任何全身治疗BCLC分期B或C期根据mRECIST标准,至少有一处可测量的靶病灶Child-Pugh评分A级ECOG-PS

0或1分良好的组织器官功能排除:肝脏占位≥50%、明显的胆管浸润或门静脉主干浸润随机1:1主要终点:OS次要终点:研究者基于mRECIST标准评估的PFS,TTP,ORR生活质量-安全性和耐 受性仑伐替尼药代动力学 暴露参数治疗直至疾病进展仑伐替尼治疗肝细胞癌患者的III期研究（REFLECT）中OS和客观缓解（OR）之间关系的分析1MasatoshiKudo,2RichardS.Finn,3ShukuiQin,4Kwang-HyubHan,5KenjiIkeda,6Ann-LiiCheng,7FabioPiscaglia,1KazuomiUeshima,8HiroshiAikata,9ArndtVogel,10CarlosLópezLópez,11MarcPracht,12ZhiqiangMeng,13BrunoDaniele,14Joong-WonPark,15DanielPalmer,16CorinaDutcus,17ToshiyukiTamai,16KenichiSaito,18RiccardoLencioni1KindaiUniversityFacultyofMedicine,Osaka,Japan;2GeffenSchoolofMedicine,UCLAMedicalCenter,SantaMonica,CA,USA;3NanjingBayiHospital,NanjingChina;4SeveranceHospital,YonseiUniversity,Seoul,RepublicofKorea;5ToranomonHospital,Tokyo,Japan;6NationalTaiwanUniversityHospitalandNationUniversityCancerCenter,Taipei,Taiwan;7UniversityofBologna,Bologna,Italy;8HiroshimaUniversityHospital,Hiroshima,Japan;9HannoverMedicalSchooGermany;10MarquésdeValdecillaUniversityHospital,Santander,Spain;11CancerInstituteEugèneMarquis,Rennes,France;12FudanUniversity,ShanghaiCanCenter,Shanghai,China;13OspedaledelMare,Napoli,Italy;14NationalCancerCenterKorea,Goyang-si,RepublicofKorea;15TheClatterbridgeCancerCentre,Birkenhead,England,UK;16EisaiInc.,WoodcliffLake,NJ,USA;17EisaiCo.,Ltd.,Tokyo,Japan;18UniversityofPisaSchoolofMedicine,Pisa,Italy;andtheMInstitute,Miami,FL,USAKudoM,et,al.Analysisofsurvivalandobjectiveresponse(OR)inpatientswithhepatocellularcarcinomainaphaseIIIstudyoflenvatinib(REFLECT)[R/OL].ASCO-GI,2019.Abstract186.背景-既往研究证实,基于mRECIST评估的OR状态是OS的独立预测因子ORR=15.6%ORR=11.5%Objective

responseNo

objective

responseObjective

responseNo

objective

responseMeyerT,etal.LiverInt.2017Jul;37(7):1047-1055.LencioniR,etal.JHepatol.2017Jun;66(6):1166-1172.研究目的和方法KudoM,et,al.Analysisofsurvivalandobjectiveresponse(OR)inpatientswithhepatocellularcarcinomainaphaseIIIstudyoflenvatinib(REFLECT)[R/OL].ASCO-GI,2019.Abstract186.研究者按mRECIST标准评估分析经仑伐替尼或索拉非尼治疗的患者OR与OS之间的关系-将应答者(CR或PR)的mOS与无应答者(SD.PD或UNK/NE)的mOS进行比较，不考虑治疗方式。-在第2、4、6个月，以OR状态为界标，使用Cox回归分析，分析OR及其他预后因素与OS之间的关系。结果-应答者mOS显著优于无应答者KudoM,et,al.Analysisofsurvivalandobjectiveresponse(OR)inpatientswithhepatocellularcarcinomainaphaseIIIstudyoflenvatinib(REFLECT)[R/OL].ASCO-GI,2019.Abstract186.根据OR状态对OS进行界标点分析均提示应答者mOS显著优于无应答者2个月界标点分析KudoM,et,al.Analysisofsurvivalandobjectiveresponse(OR)inpatientswithhepatocellularcarcinomainaphaseIIIstudyoflenvatinib(REFLECT)[R/OL].ASCO-GI,2019.Abstract186.4个月界标点分析6个月界标点分析KudREFLECT研究中OS相关预测因子的单/多变量分析参数（逐步选择）单变量分析多变量分析HR[95%

CI]P-valueHR[95%

CI]P-value肉眼可见的门静脉侵入（是vs否）1.55[1.30-1.85]<0.0011.37[1.14-1.64]<0.001基线AFP(ng/mL)(<200

vs≥200)0.52[0.45-0.61]<0.0010.56[0.48-0.66]<0.001基线时肿瘤病灶数量(2

vs

1)1.46[1.23-1.73]<0.0011.40[1.18-1.66]<0.001基线时肿瘤病灶数量(≥3

vs

1)2.24[1.84-2.72]<0.0012.02[1.66-2.47]<0.001肝脏肿瘤病灶（是vs否）2.31[1.67-3.20]<0.0011.68[1.20-2.33]0.002HBV引起(是vs否)1.23[1.06-1.43]0.0061.20[1.03-1.39]0.019HCC手术史(是vs否)0.67[0.57-0.77]<0.0010.84[0.72-0.99]0.032治疗(LEN

vs

SOR)0.93[0.80-1.077]0.3260.85[0.73-0.996]0.044客观缓解(是vs否)0

.61

[0

.49

-0

.76

]<

0

.0010

.61

[0

.49

-0

.76

]<

0

.001o

M,et,al.

Analysis

of

survival

and

objective

response

(OR)

in

patients

with

hepatocellular

carcinoma

in

a

phase

III

study

of

lenvatinib(REFLECT)[R/OL].

ASCO-GI，2019.

Abstract

186.基于非分层Cox回归分析的OS独立预测因子KudoM,et,al.Analysisofsurvivalandobjectiveresponse(OR)inpatientswithhepatocellularcarcinomainaphaseIIIstudyoflenvatinib(REFLECT)[R/OL].ASCO-GI,2019.Abstract186.结论对于HCC患者，无论接受何种治疗，基于mRECIST评估的OR状态是OS的独立预测因子-在REFLECT研究中，基于mRECIST评估的OR状态与OS的关系，其结果与既往报道相同；-对于HCC患者，其他OS的预测因子包括:MPVI、基线AFP水平、肿瘤数量、肿瘤累及部位、既往接受过至少1次治疗、治疗方式。达到OR的患者可获得更长的OS-OR状态与OS之间的关系尚需更多研究验证基于患者体重使用不同起始剂量的仑伐替尼治疗不可切除肝细胞癌的安全性和有效性（

REFLECT）TakujiOkusaka1,KenjiIkeda2,MasatoshiKudo3,RichardS.Finn4,ShukuiQin5,Kwang-HyubHan6,Ann-LiiCheng7,FabioPiscaglia8,MasahiroKobayashi2,MaxSung9,MinshanChen10,LucjanWyrwicz11,Jung-HwanYoon12,ZhenggangRen13,CorinaE.Dutcus14,ToshiyukiTamai15,MinRen14,SeiichiHayato15,HiromitsuKumada21NationalCancerCenterHospital,Tokyo,Japan;2ToranomonHospital,Tokyo,Japan;3KindaiUniversityFacultyofMedicine,Osaka,Japan;4GeffenSchoolofMedicine,UCLAMedicalCenter,SantaMonica,CA,USA;5NanjingBayiHospital,Nanjing,Jiangsu,China;6SeveranceHospital,YonseiUniversity,Seoul,RepublicofKorea;7NationalTaiwanUniversityHospital,Taipei,Taiwan;8UniversityofBologna,Bologna,Italy;9TischCancerInstituteatMountSinai,NewYork,NY,USA;10SunYat-senUniversityCancerCenter,Guangzhou,China;11CentrumOnkologii-Instytutim.,M.SklodowskiejCurie,Warsaw,Poland;12SeoulNationalUniversityHospital,Seoul,RepublicofKorea;13ZhongshanHospitalFudanUniversity,Shanghai,China;14EisaiInc.,WoodcliffLake,NJ,USA;15EisaiCo.,Ltd,Tokyo,Japan背景和目的TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316仑伐替尼Ⅱ期研究结果（202研究）显示,仑伐替尼12mg/d剂量用于不可切除的进展期肝细胞癌在早期剂量调整和体重间存在相关性,因此REFLECT研究做了依据体重的剂量调整。该研究中,受试者随机分配,其中体重<60kg的患者接受8mg/d仑伐替尼治疗剂量,体重≥60kg的患者接受12mg/d的治疗剂量。本研究旨在探讨REFLECT研究中,基于患者基线体重选择仑伐替尼起始剂量对有效性和安全性的影响TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316仑伐替尼不同起始剂量组及索拉非尼组的患者基线特征相似类别仑伐替尼8

mg

(<60

kg)(n=151)仑伐替尼12

mg

(≥60

kg)(n=325)索拉非尼(n=475)年龄中位数，年（范围）65.0

(20,

86)62.0

(24,

88)62.0

(22,

88)性别,n(%)男性女性106

(70.2)45

(29.8)297

(91.4)28

(8.6)400

(84.2)75

(15.8)地域,n(%)西方亚太21

(13.9)130

(86.1)134

(41.2)191

(58.8)156

(32.8)319

(67.2)体重,n(%)<

60

kg≥

60

kg151

(100.0)02

(0.6)323

(99.4)145

(30.5)330

(69.5)ECO

G

P

S

,

n

(%

)0193

(61.6)58

(38.4)211

(64.9)114

(35.1)301

(63.4)174

(36.6)肝功能分级,n(%)

AB151

(100.0)0322

(99.1)3

(0.9)470

(99.0)5

(1.0)肉眼可见门静脉侵犯，肝外播散，或两者兼有,n(%)是否105

(69.5)46

(30.5)223

(68.6)102

(31.4)336

(70.7)139

(29.3)BCL

C分级,n(%)

BC32

(21.2)119

(78.8)71

(21.8)254

(78.2)92

(19.4)383

(80.6)病因,n(%)乙肝丙肝酒精其他未知83

(55.0)40

(26.5)6

(4.0)8

(5.3)14

(9.3)167

(51.4)50

(15.4)30

(9.2)30

(9.2)48

(14.8)227

(47.8)126

(26.5)21

(4.4)32

(6.7)69

(14.5)基线甲胎蛋白浓度,n(%)<

200

ng/mL≥200

ng/mL未测出80

(53.0)71

(47.0)0

(0.0)174

(53.5)150

(46.2)1

(0.3)285

(60.0)187

(39.4)3

(0.6)仑伐替尼不同起始剂量亚组,与索拉非尼组间OS具有可比性体重＜60mg（仑伐替尼8mg）TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316体重≥60mg（仑伐替尼12mg）仑伐替尼不同起始剂量亚组,与索拉非尼组间PFS具有可比性体重＜60mg（仑伐替尼8mg）体重≥60mg（仑伐替尼12mg）TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316ORR在仑伐替尼不同起始剂量亚组间相似不同亚组和索拉非尼组OR具有可比性仑伐替尼8mg/d亚组vs索拉非尼组的ORR为:22.2%vs8.2%（OR=3.16；95%CI:1.56–6.41）仑伐替尼12mg/d亚组vs仑伐替尼组的ORR为:24.9%vs9.7%（OR=3.11；95%CI:2.00–4.85）仑伐替尼不同起始剂量亚组AE总体相似Study

202REFLECT仑伐替尼

12

mg(N=46)仑伐替尼<60

kg8

mg(n=151)仑伐替尼≥60

kg12

mg(n=325)索拉非尼(n=475)任何治疗期不良事件治疗相关46

(100.0)44

(95.7)151

(100.0)143

(94.7)319

(98.2)304

(93.5)472

(99.4)452

(95.2)任何治疗期不良事件≥3治疗相关45

(97.8)40

(87.0)100

(66.2)70

(46.4)257

(79.1)200

(61.5)316

(66.5)231

(48.6)任何严重不良事件治疗相关严重不良事件22

(47.8)14

(30.4)58

(38.4)20

(13.2)147

(45.2)64

(19.7)144

(30.3)48

(10.1)与治疗相关的不良事件导致患者:停药减量药物减量或中断10

(21.7)32

(69.6)N/A16

(10.6)42

(27.8)65

(43.0)26

(8.0)134

(41.2)187

(57.5)34

(7.2)181

(38.1)236

(49.7)TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316IkedaKetal.JGastroenterol.2017;52:512-519.EisaiInc.Dataonfile(Study202CSR).TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316仑伐替尼不同起始剂量亚组AE谱及AE发生率相似首选术语,n(%)仑伐替尼8

mg(<60

kg)(n=151)仑伐替尼12

mg(≥60

kg)(n=325)任何治疗期不良事件151

(100.0)319

(98.2)高血压65

(43.0)136

(41.8)腹泻53

(35.1)131

(40.3)食欲不振50

(33.1)112

(34.5)体重下降43

(28.5)104

(32.0)疲劳42

(27.8)99

(30.5)手足综合征35

(23.2)93

(28.6)蛋白尿37

(24.5)80

(24.6)发声困难28

(18.5)85

(26.2)恶心24

(15.9)69

(21.2)仑伐替尼不同起始剂量对肝功能影响评估肝功能至Child-Pugh≥7分所需时间基线5分的患者仑伐替尼8mg/12mg剂量组、索拉非尼组,中位时间未达到基线6分的患者仑伐替尼8mg剂量组中位时间与索拉非尼组相似,长于仑伐替尼12mg剂量组TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316根据治疗周期调整后,仑伐替尼不同起始剂量亚组AE谱及AE发生率相似首选术语,n(不良反应率)仑伐替尼8

mg(n=151)总持续时间=95.1年仑伐替尼12

mg(n=325)总持续时间=229.1年任何治疗期不良事件18.2619.15高血压0.790.78腹泻1.060.99食欲不振0.630.59体重下降0.500.51疲劳0.520.47手足综合征0.380.46蛋白尿0.560.48发声困难0.300.45相同的用药时间（年）,仑伐替尼不同起始剂量亚组AE谱及AE发生率相似TakujiOkusaka,etal.SafetyandEfficacyofLenvatinibbyStartingDoseBasedonBodyweightinPatients(pts)WithUnresectableHepatocellularCarcinoma(uHCC)inREFLECT.ASCO-GI2019.PosterNo.316结论不同仑伐替尼起始剂量亚组与索拉非尼组的有效性具有可比性。根据治疗周期调整AE发生率后,不同起始剂量仑伐替尼亚组的AE谱及AE发生率相似。 以上REFLECT研究结果支持仑伐替尼一线治疗8mg/d用于＜60kg、12mg/d用于≥60kg的uHCC患者。仑伐替尼治疗肝细胞癌研究中不良事件与总生存之间关系的探究（REFLECT）MaxSung1,RichardS.Finn2,ShukuiQin3,Kwang-HyubHan4,KenjiIkeda5,Ann-LiiCheng6,MasatoshiKudo7,RyosukeTateishi8,MasafumiIkeda9,ValeryBreder10,Kun-MingRau11,YukTingMa12,AngelAlsina13,Baek-YeolRyoo14,ZhenggangRen15,KalgiMody16,CorinaDutcus16,ToshiyukiTamai17,KenichiSaito16,FabioPiscaglia181TischCancerInstituteatMountSinai,NewYork,USA;2GeffenSchoolofMedicine,UCLAMedicalCenter,SantaMonica,CA,USA;3NanjingBayiHospital,Nanjing,Jiangsu,China;4SeveranceHospital,YonseiUniversity,Seoul,Korea;5ToranomonHospital,Tokyo,Japan;6NationalTaiwanUniversityHospitalandNationalTaiwanUniversityCancerCenter,Taipei,Taiwan;7KindaiUniversityFacultyofMedicine,Osaka,Japan;8TheUniversityofTokyoHospital,Tokyo,Japan;9NationalCancerCenterHospitalEast,Chiba,Japan;10NationalMedicalResearchCenterofOncologyn,a,N.N.Blokhin,Russia;11E-DAHospital,Kaohsiung,Taiwan;12QueenElizabethHospital,Birmingham,England,UK;13TampaGeneralHospital,Tampa,FL,USA;14AsanMedicalCenter,UniversityofUlsanCollegeofMedicine,Seoul,RepublicofKorea;15ZhongshanHospitalFudanUniversity,Shanghai,China;16EisaiInc.,WoodcliffLake,NJ,USA;17EisaiCo.,Ltd,Tokyo,Japan;18UniversityofBologna,Bologna,Italy背景与目的既往有多个关于不良事件与治疗药物疗效之间相关性的报道:-皮肤毒性反应是一种表皮生长因子抑制剂的常见不良事件，与临床疗效呈正相关；-有研究表明，索拉非尼不论用于转移性肾癌还是肝癌，患者中出现手足综合征者其临床疗效也明显好于未出现该不良反应者；-有研究显示，在瑞戈非尼治疗的肝癌患者中，手足综合征与OS改善有关。本研究旨在探索仑伐替尼相关的不良事件与OS之间的相关性经仑伐替尼治疗的uHCC患者出现/未出现高血压、腹泻、蛋白尿或甲状腺功能减退与OS显著相关高血压腹泻蛋白尿甲状腺功能减退出现上述不良事件的患者OS显著长于未出现者出现/未出现发声困难患者间OS无显著差异结论高血压、腹泻、蛋白尿或甲状腺功能减退可作为仑伐替尼临床获益的有效预测指标 接受仑伐替尼治疗后的uHCC患者,出现高血压、腹泻、蛋白尿或甲状腺功能减退的患者其OS显著长于未出现上述不良事件者仑伐替尼治疗不可切除肝细胞癌III期研究（REFLECT）事后分析:一线仑伐替尼治疗后的后续抗癌治疗AngelAlsina1,MasatoshiKudo2,ArndtVogel3,Ann-LiiCheng4,WonYoungTak5,Baek-YeolRyoo6,TRJeffryEvans7,CarlosLópezLópez8,BrunoDaniele9,SoamnauthMisir10,MinRen10,NamikiIzumi11,ShukuiQin12,RichardS.Finn131TampaGeneralHospital,Tampa,FL,USA;2KindaiUniversityFacultyofMedicine,Osaka,Japan;3HannoverMedicalSchool,Hannover,Germany;4NationalTaiwanUniversityHospitalandNationalTaiwanUniversityCancerCenter,Taipei,Taiwan;5SchoolofMedicine,KyungpookNationalUniversity,Daegu,RepublicofKorea;6AsanMedicalCenter,UniversityofUlsanCollegeofMedicine,Seoul,RepublicofKorea;7UniversityofGlasgow,BeatsonWestofScotlandCancerCentre,Glasgow,UK;8MarquésdeValdecillaUniversityHospital,Santander,Spain;9OspedaledelMare,Napoli,Italy,10EisaiInc.,WoodcliffLake,NJ,USA;11MusashinoRedCrossHospital,Musashino,Tokyo,Japan;12NanjingBayiHospital,Nanjing,Jiangsu,China;13GeffenSchoolofMedicine,UCLAMedicalCenter,SantaMonica,CA,USAKudoM,et,al.Subsequentanticancermedicationfollowingfirst-linelenvatinib:Aposthocresponderanalysisfromthephase3REFLECTstudyinunresectablehepatocellularcarcinoma.ASCO-GI2019.PosterNo.371背景和目的 仑伐替尼是十多年来首个批准用于不可切除HCC的一线治疗药物。其关键Ⅲ期REFLECT研究达到主要终点，仑伐替尼相比索拉非尼治疗的总生存（OS）在统计学上具有非劣效性（中位OS:13.6个月vs.12.3个月；风险比[HR]:0.92；95%置信度区间[CI]:0.79-1.06）。在次要终点无进展生存、至疾病进展时间、客观缓解率（ORR）方面，仑伐替尼显著优于索拉非尼。 一线和后续治疗中新治疗选择的出现改变了不可切除肝癌的治疗模式，这对药物的合理选择以及抗癌治疗时间及顺序等相关问题带来了挑战。 该事后分析评估REFLECT研究中，仑伐替尼组和索拉非尼组接受后续抗癌治疗的患者的OS；以及对仑伐替尼或索拉非尼有应答的患者后续接受抗癌治疗的情况。KudoM,et,al.Subsequentanticancermedicationfollowingfirst-linelenvatinib:Aposthocresponderanalysisfromthephase3REFLECTstudyinunresectablehepatocellularcarcinoma.ASCO-GI2019.PosterNo.371结果-约1/3患者接受后续抗癌药物治疗在生存随访期间,仑伐替尼组和索拉非尼组中分别有33%和39%的患者接受了后续抗癌药物治疗药物治疗,n(%)仑伐替尼(n=478)索拉非尼(n=476)在生存随访期间接受抗癌药物治疗的患者156

(32.6)184

(38.7)索拉非尼121

(25.3)56

(11.8)氟尿嘧啶20

(4.2)26

(5.5)顺铂18

(3.8)23

(4.8)研究药物15

(3.1)45

(9.5)奥沙利铂14

(2.9)22

(4.6)多柔比星7

(1.5)19

(4.0)卡培他滨7

(1.5)11

(2.3)吉西他滨7

(1.5)14

(2.9)卡博替尼0

(0)11

(2.3)对于一线接受仑伐替尼治疗的患者,索拉非尼是最常见的后续抗癌治疗药物,25%的患者在生存随访期间接受了索拉非尼治疗。而索拉非尼组有12%的患者在生存随访期间重新开始或继续使用索拉非尼。仑伐替尼组有3%患者接受了其他在研抗癌药物治疗,而索拉非尼组为10%。使用仑伐替尼治疗的患者后续接受在研药物治疗的机会有限,因为通常二线治疗的临床试验（如瑞戈非尼或卡博替尼）要求受试者一线索拉非尼治疗失败。KudoM,et,al.Subsequentanticancermedicationfollowingfirst-linelenvatinib:Aposthocresponderanalysisfromthephase3REFLECTstudyinunresectablehepatocellularcarcinoma.ASCO-GI2019.PosterNo.371治疗中止时,仑伐替尼组和索拉非尼组患者状态相似参数仑伐替尼索拉非尼亚太地区(N=308)西方

(N=143)亚太地区(N=304)西方

(N=147)ECOG

PS评分,n(%)

012≥

3120

(39.0)153

(49.7)22

(7.1)13

(4.2)45

(31.5)67

(46.9)20

(14.0)9

(6.3)135

(44.4)132

(43.4)23

(7.6)14

(4.6)54

(36.7)70

(47.6)16

(10.9)6

(4.1)肝功能分级,n(%)

ABC233

(75.6)67

(21.8)8

(2.6)106

(74.1)30

(21.0)5

(3.5)235

(77.3)65

(21.4)4

(1.3)110

(74.8)34

(23.1)2

(1.4)ALT中位数,U/L(范围)a30.0

(3–390)42.0

(9–726)38.0

(6–1032)40.5

(13–1105)AST中位数,U/L(范围)a47.0

(14–470)65.0

(10–2501)59.0

(13–1211)58.5

(17–1065)ALP中位数,U/L(范围)a123.0

(25–885)166.0

(42–1857)130.5

(41–972)169.0

(28–1457)胆红素中位数,μmol/L(范围)a12.1

(2–276)15.2

(3–643)12.2

(3–408)13.3

(3–153)白蛋白中位数,

g/L(范围)a38.0

(21–51)37.0

(19–51)38.0

(22–52)37.0

(19–49)aIn

the

western

region,

2

patients

from

the

lenvatinib

arm

and

1

patient

from

the

sorafenib

arm

had

no

data.ALP,

alkaline

phosphata