晚期NSCLC维持治疗策略课件.ppt

1、诊断缓解或稳定PD死亡1线化疗(4-6周期)2-3线化疗Socinski MA,et al.J Clin Oncol 2002;20:13351343.Park JO,et al.J Clin Oncol 2007;25:52335239.von Plessen et al.Br J Cancer 2006;95:966973.Park JO,et al.J ClinOncol 2007;25:52335239 第一作者第一作者年份年份化疗化疗治疗组治疗组(n)TTPMST1YSSmith2001MVP3周期周期(155)6周期周期(153)5月月5月月6月月7月月22%25%Socinski

2、2002CP4周期周期(114)持续持续(116)NRNR6.6月月8.5月月28%34%Von Plessen2006CV3 周期周期(150)6周期周期(147)16周周21周周7月月8月月25%25%Park2007铂类铂类4周期周期(156)6周期周期(158)4.6月月6.2月月15.9月月14.9月月62.4%59%Smith et al：6周期=31%Socinsk et al:6周期=13%Park et al：6周期=68%Von Plessen et al:6周期=54%Socinski MA,et al.J Clin Oncol 2002;20:13351343JCO 2

3、009;27:3277-3283199720042009ASCO Educational Book 2003诊断缓解或稳定PD死亡1线化疗(4-6周期)2-3线化疗？诊断缓解或稳定PD死亡1线化疗(4-6周期)2-3线化疗？方式研究维持药物Median PFS(月)对照组原药维持Brodowics 吉西他滨2IFCT-GFPC吉西他滨1.9Belani吉西他滨7.7Parament培美曲赛2.6换药维持Westeel Vinorelbine 3Fidias 多西他赛2.7Ciuleanu 培美曲赛2JMEN培美曲赛1.8靶向维持SATURN厄洛替尼2.6INFORM吉非替尼2.6Fidias

4、JCO 27:591-8,2009Ciuleanu Lancet 374:1432-40,2009Capuzzo Lancet Oncol 11:521-529,2010 J Clin Oncol 29:2011(suppl;abstr CRA7510)Belani,ASCO 2010Perol,ESMO,2010Ciuleanu,et al.The Lancet 2009Cappuzzo,et al.ASCO 2009Zhang L,et al.2011 ASCO Abstract 7511.主要原因PS差(58%)一线治疗疗效差(24%)合并症(24%)痌变范围(22%)29%仅接受 BS

5、C 接受一线治疗的患者100%54%接受二线治疗的患者来自306位欧盟医师的资料 46%未接受二线治疗 17%死亡TNS Healthcare,Brand Tracking Study,December 20071008060402001.J Clin Oncol 2002;20:133543;2.J Clin Oncol 2003;21:293339;3.Lung Cancer 2006;52:15563;4.Br J Cancer 2006;95:96673;5.J Thorac Oncol 2007;2(Suppl.4):S666(Abs.P2-235);6.J Clin Oncol 2

6、007;25:523339;7.Lancet 2009;374:143240;8.J Clin Oncol 2008;26(Suppl.15):6s(Abs.3);9.J Clin Oncol 2008;26:354351;10.J Clin Oncol 2009;27:5919802550 75100Socinski et al.20021Belani et al.20032Brodowicz et al.20063von Plessen et al.20064Barata et al.20075Park et al.20076Ciuleanu et al.20097Pirker et al

7、.20088Scagliotti et al.20089Fidias et al.200910接受二线治疗的患者接受二线治疗的患者(%)Stinchcombe,Socinski,JTO 2011诊断PD二线治疗直到PD死亡一线治疗含铂两药化疗(46周期)CR/PR/SD维持治疗新的治疗模式：维持治疗方式研究维持药物Median PFS(月)HR(95%CL)for PFS对照组维持组原药维持Brodowics 吉西他滨23.60.69(0.56-0.86)IFCT-GFPC吉西他滨1.93.80.56(0.44-0.72)Belani吉西他滨7.77.41.09(0.81-1.45)Param

8、ent培美曲赛2.63.90.64(0.51-0.81)换药维持Westeel Vinorelbine 350.77(0.55-1.07)Fidias 多西他赛2.75.70.71(0.55-0.92)JMEN培美曲赛1.84.40.47(0.420.61)靶向维持SATURN厄洛替尼2.62.90.71(0.620.82)INFORM吉非替尼2.64.80.42(0.33-0.55)Fidias JCO 27:591-8,2009Ciuleanu Lancet 374:1432-40,2009Capuzzo Lancet Oncol 11:521-529,2010 J Clin Oncol

9、29:2011(suppl;abstr CRA7510)Belani,ASCO 2010Perol,ESMO,2010Ciuleanu,et al.The Lancet 2009Cappuzzo,et al.ASCO 2009Zhang L,et al.2011 ASCO Abstract 7511.Zhang L,et al.2011 ASCO Abstract 7511.0312 152125时间(月)无进展生存率(%)02040608010018698.5 易瑞沙(n=105)2.6 安慰剂(n=104)中位 PFS(月)AstraZeneca Data On File.16.6 易瑞沙

10、(n=15)2.8 安慰剂(n=15)中位 PFS(月)01696112PFS概率(%)04060801002032486480自随机时间(周)4.8 易瑞沙(n=148)2.6 安慰剂(n=148)中位 PFS(月)HR=0.42HR=0.17全组人群腺癌亚组EGFR M+亚组Odds Ratio=3.31(95%CI 1.60-6.82,p=0.0012).中位症状恶化时间(LCS):4.3月(gefitinib)v 2.3月(placebo).INFORM生活质量改善Han BH,et al WCLC 2011方式研究维持药物Median OS(月)HR(95%CL)for OS对照组维

11、持组原药维持Brodowics 吉西他滨11.0 13.0 p=0.195IFCT-GFPC吉西他滨10.8 12.1 0.86(0.66-1.12)Belani吉西他滨8.0 9.3 0.97(0.72-1.30)Parament培美曲赛NRNRNR换药维持Westeel Vinorelbine 12.3 12.3 p=0.65Fidias 多西他赛9.7 12.3 0.84(0.651.08)JMEN培美曲赛10.6 13.4 0.70(0.56-0.88)靶向维持SATURN厄洛替尼11.0 12.0 0.81(0.700.95)INFORM吉非替尼16.9 18.7 0.84(0.62

12、1.14)Fidias JCO 27:591-8,2009Ciuleanu Lancet 374:1432-40,2009Capuzzo Lancet Oncol 11:521-529,2010 J Clin Oncol 29:2011(suppl;abstr CRA7510)Belani,ASCO 2010Perol,ESMO,2010Ciuleanu,et al.The Lancet 2009Cappuzzo,et al.ASCO 2009Zhang L,et al.2011 ASCO Abstract 7511.研究分组中位PFS(月)中位OS(月)任何后续治疗(%)后续为维持治疗药物(

13、%)JMEN培美曲塞413.4511安慰剂210.66718SATURN特罗凯2.912555安慰剂2.6116416Fidias多西他赛维持5.712.395多西他赛二线2.79.763IFCT-GFPC特罗凯2.9682观察组1.98254INFORM吉非替尼4.818.750.78.1观察组2.616.966.931.8Time(weeks)0 8 16 24 32 40 48 56 64 72 80 88 96PFS probabilityHR=0.10(0.040.25)Log-rank p0.0001 1.00.80.60.40.20PFSErlotinib(n=22)Placeb

14、o(n=27)Cappuzzo,et al.ASCO 2009Coudert,etal.ELCC2010AuthorStudyN(EGFR mut+)RR Median PFSOSMok et alIPASS13271.2%vs 47.39.8 vs 6.4 months阴性Lee et alFirst-SIGNAL2784.6%vs 37.5%8.4 vs 6.7 months阴性Mitsudomi et alWJTOG 34058662.1%vs 32.2%9.2 vs 6.3 months阴性Maemondo et alNEJGSG00211473.7%vs 30.7%10.8 vs 5

15、.4 months阴性Zhou et alOPTIMAL15483%vs 36%13.1 vs 4.6 months阴性Rosell et alEURTAC135NANA阴性Mok et al NEJM 2009,Lee et al WCLC 2009,Mitsudomi et al Lancet Oncology 2010,Maemondo NEJM 2010Zhou et al ESMO 2010，Rosell et al ASCO 2011Ciuleanu,et al.The Lancet 2009PerolM,etal.ESMO:abstr370PD.观察组(N=155)吉西他滨(N=

16、154)特罗凯(N=155)培美曲塞(%)766063中位周期(范围)3(1-14)3(1-21)3(1-14)二线培美曲塞疗效可评估患者796267 CR(%)001.5 PR(%)15.28.110.4 SD(%)43.046.840.3 PD(%)41.847.247.8Perol M,et al.J Clin Oncol 2010;28(s):abstr 7507.全全组组病人病人接受二接受二线线治治疗疗的的病人病人Perol M,et al.J Clin Oncol 2010;28(s):abstr 7507.JTO 2011;6:365371JCO 20111.哪些患者适合维持治疗

17、？2.原药维持和换药维持如何选择？3.怎样实现个体化维持治疗?吉西他滨/卡铂一线治疗后吉西他滨维持IFCT-GFPC 0502研究吉西他滨维持组N=128BSCN=127吉西他滨维持组N=154BSCN=155中位年龄（岁）67.267.557.959.8ECOG PS 2-3(%)565863对诱导化疗的反应:ORR/SD(%)28/3753/4753/47PFS(月)3.93.83.81.9P=0.838*P0.001OS(月)8.09.3NR*与安慰与安慰剂剂相比相比ASCO 2010 M.Perol,et al.,Abstract#7507ASCO 2010 C.P.Belani,et

18、 al.,Abstract#7506HR=0.47 95%CI:0.420.61)p 0.00001Progression-free probability培美曲塞:中位=4.4个月 安慰剂:中位=1.8个月 1.0036912150.00.10.20.30.40.50.60.70.80.91.0培美曲塞:中位=3.9个月(3.0-4.2)安慰剂:中位=2.6个月(2.2-2.9)Log-rank P=0.0002未调整HR:0.64(0.51-0.81)JNENParamountTime（months）Time（months）Progression-free probability从延长 P

19、FS角度来看，两种治疗方式都是合理的选择。Ciuleanu,et al.The Lancet 2009Ciuleanu,et al.The Lancet 2009Cappuzzo,et al.ASCO 2009Cappuzzo et al.Lancet Oncol 2010;Brugger,et al.WCLC 2009Time(weeks)0 8 16 24 32 40 48 56 64 72 80 88 96PFS probabilityHR=0.10(0.040.25)Log-rank p0.0001 1.00.80.60.40.20PFSErlotinib(n=22)Placebo(n

20、=27)020406080100081624324048566472808896 104 112PFS(%)时间(周)HR(95%CI)=0.17(0.07,0.42)吉非替尼(n=15)中位 PFS,16.6 个月安慰剂(n=15)中位 PFS,2.8 个月1.“Switch maintenance”Tx with erlotinib or pemetrexed following completation of first-line CT is an option.Decision factors for the use of“switch maintenance”include hist

21、ology,type and response to first line chemotherapy,residual toxicity,patients symptoms and preference.2.Any patient whose tumor harbour an EGFR activating mutation should receive EGFR TKIs as maintenance,if not yet received as first-line.Strength of recommendation:B;Level of evidence:I 此课件下载可自行编辑修改，供参考！感谢您的支持，我们努力做得更好！