肿瘤维持治疗进展

Click to edit Master text styles,Second level,Third level,Click to edit Master title style,一、背景,NSCLC,治疗模式,传统的,NSCLC,治疗模式,确诊,CR,PR,SD,PD,PD,观察、等待,二线或后续,一线,很多患者由于症状及体力状态的快速恶化而不接受更多的治疗,100,例,一线含铂化疗,75,例,临床获益,观察、等待,2-3,个月,38,例,二线治疗,Stinchcombe,的研究,能接受后续治疗,的患者才最有可,能从治疗中获得,生存的益处,.,新的,NSCLC,治疗模式,确诊,CR,PR,SD,PD,PD,一线,维持治疗,二线或后续,二、主要内容,NSCLC,的,维持治疗,NSCLC,维持治疗的定义,继续维持治疗,换药维持治疗,4-6,周期含铂两药一线化疗,有效或病情稳定,至少一种,一线药物治疗,另一种非,一线药物治疗,NSCLC,维持治疗的目的,延长疾病进展,预防症状恶化,维持体力状态，使患者能接受更多的治疗,延长总生存期,NSCLC,维持治疗的特点,有效,耐受良好,积极治疗,/,风险比,NSCLC,维持治疗的常用药物,厄罗替尼,多西他赛,贝伐珠单抗,西妥西单抗,培美曲塞,吉非替尼,维持治疗,NSCLC,维持治疗,研究现状,多西他赛,（,Fidia,研究,）,Randomise,Treated,ORR 29%,Off Study,n=245,IIIb /IV NSCLC,n=562,GC,n=552,(388 received 4 cycles),SD, PR, CR,n=307,延迟治疗组,n=154,延迟多西他赛治疗,n=91,立即多西他赛治疗,n=142,立即治疗组,n=153,HR=0.71(0.550.92),Log-rankp=0.0001,Immediate,(n=153),Delayed,(n=154),LR,p-Value,Median PFS months,(95% CI),6.5,(4.4, 7.2),2.8,(2.6, 3.4),0.0001,12-month PFS, %,(95% CI),20%,(13, 26),9%,(5, 14),延迟多西他,赛,(n=156),立即多西他,赛,(n=153),时,间,（,月,）,0 6 12 18 24 30 36 42 48,1.0,0.8,0.6,0.4,0.2,0,概,率,图,1,立即治疗组与延迟治疗组,PFS,比较,注：用多西他赛维持治疗能延长,NSCLC,患者无进展生存时间,立即多西他,赛,(n=153),延迟多西他,赛,(n=156),1.0,0.8,0.6,0.4,0.2,0,时间,(,月,),0,6,12,18,24,30,36,42 48,54,60,HR=0.84(0.651.08),Log-rankp=0.085,图,2,立即治疗组与延迟治疗组,OS,比较,培美曲塞,（,JMEN,研究,）,2:1,R,培美曲塞,+ BSC,(n=441),主要终点：,PFS,安慰剂,+ BSC,(n=222),IIIB/IV NSCLC,PS 0-1,CR/PR/SD,Non-squamous,Time (months),PFS probability,0 3 6 9 12 15 18 21 24,1.0,0.8,0.6,0.4,0.2,0.0,Pemetrexed,Placebo,HR=0.47 (0.37,0.6),Log-rank p0.00001,4.4,1.8,图,3,培美曲塞组与安慰剂组,PFS,比较,注：用培美曲塞维持治疗显著延长,NCLC,中非鳞癌患者无进展生存时间,Survival Time (months),Nonsquamous,Pemetrexed,Median = 14.4,months,Placebo:,Median = 9.4 months,HR=0.66,(95% CI: 0.49,0.88),p=.005,Survival Time (months),Survival Probability,图,4,培美曲塞组与安慰剂组,OS,比较,注：用培美曲塞维持治疗显著延长,NCLC,中非鳞癌患者总生存时间,表,1,培美曲塞组与安慰剂组治疗有效率比较,注：用培美曲塞维持治疗能使,NCLC,患者治疗有效率提高,培美曲塞,+,顺铂,x4,周期,Non-PD,(n,=539),安慰剂,(n=180),培美曲塞,(n=359),PD,IIIB/IV NSCLC,非鳞癌,(n=939),培美曲塞,（,PARAMOUNT,研究）,PD,2011,年,ASCO,Pemetrexed : median =4.1 mos (3.2-4.6),Placebo: median =2.8 mos (2.6-3.1),Log-rank,P,=0.00006,Unadjusted HR: 0.62 (0.49-0.79),Pem + BSC,Placebo + BSC,图,5,培美曲塞组与安慰剂组,PFS,比较,注：用培美曲塞维持治疗显著延长,NCLC,患者无进展生存时间,Pemetrexed,(N=316),n (%),Placebo(N=156),n (%),P-value,CR,0,0,PR,9 (2.8),1 (0.6),RR: CR+PR,9 (2.8),1 (0.6),0.176,SD,218 (69.0),92 (59.0),DCR: CR+PR+SD,227 (71.8),93 (59.6),0.009,PD,88 (27.8),61 (39.1),Other / ND,1 (0.3),2 (1.3),表,2,培美曲塞组与安慰剂组治疗疗效比较,注：用培美曲塞维持治疗能使,NCLC SD,患者治疗有效率明显提高,吉西他滨、特罗凯,（,IFCT-GFPC0502,研究）,主要终点：,PFS,CR,PR,SD,NSCLC,IIIB,期,-IV,期,顺铂,+,吉西他滨,x4,周期,(N=834),PD,PD,PD,R,N=464,观察组,N=155,吉西他滨组,N=154,特罗凯组,N=155,维持治疗,二线治疗,培美曲塞,培美曲塞,培美曲塞,Observation,Gemcitabine,HR=0.55 (0.430.70),Log-rank test p0.0001,3.8,PFS probability,Time (months),1.0,0.8,0.6,0.4,0.2,0.0,0 5 10 15 20 25 3035 40,1.9,图,6,吉西他滨组与安慰剂组,PFS,比较,注：用吉西他滨维持治疗能延长,NCLC,患者,无进展生存时间,0,0.2,0.4,0.6,0.8,1.0,0,10,20,30,40,PFS,概率,时间（月）,HR=0.83(0.73-0.94),log-rank test: p=0.002,观察组,特罗凯,图,7,特罗凯组与安慰剂组,PFS,比较,注：用特罗凯维持治疗能延长,NCLC,患者,无进展生存时间,1:1,晚期,NSCLC,n,=,1,949,非,PD,n,=889,4,周期含铂,一线化疗,安慰剂,PD,特罗凯,PD,特罗凯,（,SATURN,研究）,PFS probability,Time (weeks),081624324048566472808896,Time (weeks),081624324048566472808896,1.0,0.8,0.6,0.4,0.2,0,1.0,0.8,0.6,0.4,0.2,0,HR=0.81 (0.700.95),Log-rank p=0.0088,Erlotinib (n=438),Placebo (n=451),OS probability,图,8,特罗凯组与安慰剂组,PFS,、,OS,比较,HR=0.71 (0.620.82),Log-rank p0.0001,Erlotinib (n=437),Placebo (n=447),注：用特罗凯维持治疗能延长,NCLC,患者,无进展生存时间和总生存时间,OS probability,1.0,0.8,0.6,0.4,0.2,0,0369121518212427303336,Time (months),11.9,12.5,SD,安慰剂组,(n=235),CR/PR,安慰剂组,(n=210),SD,特罗凯组,(n=252),CR/PR,特罗凯组,(n=184),特罗凯维持治疗给,SD,患者,应有的生存时间,特罗凯,（,SATURN,研究）,图,9,特罗凯组,SD,患者与安慰剂组,SD,患者,OS,比较,1.0,0.8,0.6,0.4,0.2,0,0369121518212427303336,Time (months),10.6,13.7,HR=0.76 (0.591.00),Log-rank p=0.0457,Tarceva (n=155),Placebo (n=142),HR=0.67 (0.480.92),Log-rank p=0.0116,Tarceva (n=97),Placebo (n=93),OS probability,1.0,0.8,0.6,0.4,0.2,0,0369121518212427303336,Time (months),8.3,11.3,图,10,鳞癌特罗凯组与安慰剂组,OS,比较,图,11,非鳞癌特罗凯组与安慰剂组,OS,比较,Log-rank p=0.2285,22.1,1.0,0.8,0.6,0.4,0.2,0,0369121518212427303336,Time (months),Tarceva (n=15) Placebo (n=15),HR=0.48 (0.141.62),OS probability,Time (months),0369121518212427303336,1.0,0.8,0.6,0.4,0.2,0,8.7,12.4,Tarceva (n=114),Placebo (n=103),HR=0.65 (0.480.87),Log-rank p=0.0041,图,12,野生型,NSCLC,特罗凯组与安慰剂组,OS,比较,图,13,突变型,NSCLC,特罗凯组与安慰剂组,OS,比较,OS probability,Time (weeks),08162432404856647280,88,96,PFS probability,1.0,0.8,0.6,0.4,0.2,0,PFS,HR=0.10 (0.040.25),Log-rank p0.0001,Erlotinib (n=22),Placebo (n=27),0369121518212427303336,1.0,0.8,0.6,0.4,0.2,0,Time (months),OS,HR=0.83 (0.342.02),Log-rank p=0.6810,Erlotinib (n=22),Placebo (n=27),OS probability,图,14,厄罗替尼组中,EGFR mut +,亚组与安慰剂组,PFS,、,OS,比较,1:1,Non-PD,n,=296,含铂,x4,周期,安慰剂,PD,吉非替尼,PD,IIIB/IV,NSCLC,吉非替尼,（,INFORM,）,HR (95% CI) =,0.42,(0.33, 0.55); p80,分；,3,、对于非鳞癌亚型，选培美曲塞或特罗凯较佳；,4,、对于,EGFR,突变型，应首选,EGFR-TKI,。,小结,