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1、1中山大学肿瘤防治中心 SUN YAT-SEN UNIVERSITY CANCER CENTER晚期非小细胞肺癌维持治疗 Why？ Who？ 中山大学附属肿瘤医院 张力新的治疗模式EGFR TKIchemo +/- 贝贝伐EGFR mut +veEGFR mut ve or unknown晚期 NSCLC挽救治疗疗PR or SD下一步？PDSD = stable diseasel一线线化疗疗后“等待”的结结果（来自随机III期临临床研究）：l 50%患者在停止治疗疗后的2个月内疾病进进展l 到1/3的患者由于各种原因未能接受二线线治疗疗晚期肺癌治疗的模式4个周期以后的化疗没有显著增加疗效作者
2、 年份研究设计中位生存 (月)1年生存率 (%)PDipierre 2001诱导化疗缓解的患者 观察 Vs. 长春瑞滨12.5 10.553% 40%NSSocinski 2001卡铂/紫杉醇： 4周期 Vs. 持续使用直到PD6.6 8.528% 34%0.63Smith 2001MVP 3周期 Vs. 6周期6 722% 25%0.2l 增加化疗周期没有显著提高缓解率并改善生存期维持治疗下一步贝伐单抗（如果患者使 用化疗贝伐单抗）观察直到进展维持治疗TKI维持治疗化疗维持治疗6中山大学肿瘤防治中心 SUN YAT-SEN UNIVERSITY CANCER CENTER维持治疗 Why？
3、IIIb/IV NSCLCn=562 Off Study n=245 Fidias：多西他赛维持治疗RandomisedTreatedORR 29%Fidias et al, J Clin Oncol 2008GC phase n=552 (388 received 4 cycles) SD, PR, CR n=307Delayed n=154Delayed treated n=91Immediate treated n=142Immediate n=153Fidias：多西他赛维持治疗Fidias,etal.JCO2009立即多西他赛(n=153)延迟多西他赛(n=156)1.00.80.6
4、0.40.20概率时间(月)0 6 12 18 24 30 364248HR=0.71(0.550.92) Log-rankp=0.0001Immediate (n=153)Delayed (n=154)LRp-ValueMedian PFS months (95% CI)6.5(4.4, 7.2)2.8(2.6, 3.4)0.000112-month PFS, % (95% CI)20%(13, 26)9%(5, 14)JMEN：培美曲赛维持治疗lStage IIIB/IV NSCLClPS 0-1 l4 prior cycles of gem, doc, or tax + cis or c
5、arb, with CR, PR, or SDRandomisation factors: lgenderlPSlstagelbest tumour response to inductionlnon-platinum induction druglbrain mets2:1 RandomisationPemetrexed 500mg/m2 (d1,q21d) + BSC (n=441)*Primary Endpoint = PFSPlacebo (d1, q21d) + BSC (n=222)*B12, folate, and dexamethasone given in both arms
6、Ciuleanu et al Lancet 2009Non-squamous Non-squamous Time (months) PFS probability0 3 6 9 12 15 18 21 241.00.80.60.40.20.0PemetrexedPlaceboHR=0.47 (0.370.6) Log-rank p0.000014.41.8Ciuleanu et al Lancet 2009JMEN：培美曲赛维持治疗IFCT-GFPC0502研究:试验设计NSCLC 湿性IIIB期-IV期 PS0-1 18-70岁主要终点：PFS顺铂+ 吉西他滨 x4周期 (N=834)如PD
7、则出组CR PR SDR观察组 N=155吉西他滨组 N=154特罗凯组 N=155PDPDPD进展后的 二线治疗维持治疗培美曲塞培美曲塞培美曲塞N=464PerolM,etal.ESMO:abstr370PD.吉西他宾维持治疗:PFS in PS 01PFS is measured from time of randomisation into the maintenance phaseObservationGemcitabine HR=0.55 (0.430.70) Log-rank test p0.00013.8PFS probabilityTime (months) 1.00.80.6
8、0.40.20.00 5 10 15 20 25 3035401.9M. Prol, et al. et al. 35th Annual Congress of the European Society for Medical Oncology, 812 October 2010, Milan, Italy. Abstract 370PD.独立评审：特罗凯 vs. 观察组00.20.40.60.81.0010203040PFS概率时间（月）HR=0.83(0.73-0.94) log-rank test: p=0.002观察组特罗凯2:1Non-PD n=539Pemetrexed 500 m
9、g/m2 + cisplatin 75 mg/m2, d1 q3d, x4 cyclesPlaceboPDPemetrexed 500 mg/m2 d1 q3wPDlChemonaivelStage IIIB/IV NSCLClNon-squamous histologylECOG PS 01(n=939)PARAMOUNT; S124; NCT00789373l First-line maintenance advanced NSCLCl Phase III, randomised, double blind, placebo-controlledl Primary endpointPFSl
10、Secondary endpointsOSORREQ-5DResource utilisationSafetyPaz-Ares LG et al. J Clin Oncol 2011;29 (suppl):abstract CRA7510.2011年ASCO最新研究报道 PARAMOUNT研究设计StratificationlNSCLC stagelPSlResponse to inductionPARAMOUNT: Investigator Assessed PFS (from Maintenance)Pemetrexed: median =4.1 mos (3.2-4.6) Placebo
11、: median =2.8 mos (2.6-3.1) Log-rank P=0.00006 Unadjusted HR: 0.62 (0.49-0.79)Pem + BSCPlacebo + BSCSATURN研究设计Stratification factors:lEGFR IHC (positive vs negative vs indeterminate)lStage (IIIB vs IV)lECOG PS (0 vs 1)lCT regimen (cis/gem vs carbo/doc vs others)lSmoking history (current vs former vs
12、 never)lRegionCo-primary endpoints:lPFS in all patientslPFS in patients with EGFR IHC+ tumoursSecondary endpoints:lOS in all patients and those with EGFR IHC+ tumours, OS and PFS in EGFR IHC tumours; biomarker analyses; safety; time to symptom progression; quality of life 1:1Chemonave advanced NSCLC
13、 n=1,949Non-PD n=8894 cycles of 1st-line platinum- based doublet* PlaceboPDErlotinib 150mg/dayPDMandatory tumour samplingCapuzzo et al Lancet Oncol 2010特罗凯维持治疗PFS和OSPFS probabilityTime (weeks)08 16 24 32 40 48 56 64 72 80 88 96Time (weeks)08 16 24 32 40 48 56 64 72 80 88 96HR=0.71 (0.620.82) Log-ran
14、k p0.0001HR=0.81 (0.700.95) Log-rank p=0.00881.00.80.60.40.201.00.80.60.40.20OSPFSErlotinib (n=437) Placebo (n=447)Erlotinib (n=438) Placebo (n=451)OS probabilityCapuzzo et al Lancet Oncol 2010Zhang L et al. J Clin Oncol 2011;29 (suppl):abstract LBA7511.INFORM; C-TONG 0804; D7913L00071; NCT00770588I
15、NFORM研究设计1:1Non-PD n=296Platinum-based doublet chemotherapy*q3d, x4 cyclesPlaceboPDGefitinib 250md/dayPDlChemonavelStage IIIB/IV NSCLClWHO PS 02lChinese patientslFirst-line maintenance advanced NSCLClPhase III, randomised, multicenter, parallel group, placebo-controlledlPrimary endpointPFSlSecondary endpointsOSORRDCRHealth-related QoLSafety*Cisplatin or carboplatin plus either gemcitabine, paclitaxel, docetaxel or vinorelbineINFORM：PFS (ITT)HR (95% CI) = 0.42 (0.33, 0.55); p0.0001吉非替尼 (n=148)安慰剂 (n=148)中位 PFS, 月 6-个月 PFS, % 12-个月 PFS, %4.8 47.3 33.22.6 15
