特罗凯发展历程课件

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1、特罗凯发展历程特罗凯发展历程BR.21晚期晚期NSCLC的治疗目标的治疗目标l活得更长活得更长延长总生存期延长总生存期l活得更好活得更好改善症状改善症状延长肿瘤进展时间延长肿瘤进展时间 提高疾病控制率提高疾病控制率减少毒性减少毒性提高生活质量提高生活质量 (QoL)(QoL)BR.21BR.21之前的晚期之前的晚期NSCLCNSCLC的二线治疗的二线治疗l化疗化疗多西他赛多西他赛培美曲塞培美曲塞l靶向靶向吉非替尼吉非替尼TAX 317: OS - 7.5 vs. 4.6*; 1YS - 37% vs. 12%* TAX 320: 1YS - 32% vs. 19%* JMEI: OS- 8.3

2、 vs. 7.9; 1YS - 29.7% vs. 29.7%*ISEL: OS 5.6 vs. 5.1*; 1YS 27% vs. 21%* 与最佳支持治疗比，p0.05* 与长春瑞滨或异环磷酰胺比，p0.05* 与安慰剂比，p0.05BR21BR21：研究设计：研究设计全球多中心、前瞻、全球多中心、前瞻、IIIIII期期 n=731确诊的NSCLCIIIB或IV期体力状态评分：体力状态评分：PS0-3PS0-3足够器官功能无未受控制的脑转移年龄不小于18岁具有可/不可测量病灶既往1-2次化疗但不包括既往接受EGFR-TKI的治疗特罗凯特罗凯150mg/d150mg/d(n=488)(n=4

3、88)安慰剂安慰剂(n=243)(n=243)随机分组2 21 1l主要终点：总生存期主要终点：总生存期Shepherd FA et al, N Engl J Med 2005; 353:123-132.Shepherd FA et al, N Engl J Med 2005; 353:123-132.BR21BR21：基线特征：基线特征特罗凯(n=488)安慰剂(n=243)中位年龄，岁625960，%42.651.0男性，%64.565.8亚裔，%12.912.2PS 2 / 3 3，%25.8 / 8.623.0 / 8.6腺癌 / 鳞癌，%50.4 / 29.549.0 / 32.1既

4、往化疗1 / 2 2次以上次以上，%50.6 / 49.450.2 / 49.8既往化疗 RR / SD / PDPD，%38.1 / 34.0 / 27.937.9 / 34.2 / 28.0吸烟 / 不吸烟73.4 / 21.377.0 / 17.3Shepherd FA et al, N Engl J Med 2005; 353:123-132.Shepherd FA et al, N Engl J Med 2005; 353:123-132.特罗凯显著延长特罗凯显著延长OSOS达达42.5%42.5%Shepherd FA, et al. N Engl J Med 2005;353:1

5、23-132.Shepherd FA, et al. N Engl J Med 2005;353:123-132.*HR and p (*HR and p (log-rank test) log-rank test) adjusted for stratificationadjusted for stratificationfactors at randomisation and EGFR statusfactors at randomisation and EGFR statusOS: 42.5%OS: 42.5%OS: 42.5%OS: 42.5%1YS: 45%1YS: 45%1YS:

6、45%1YS: 45%Hazard ratio (HR)=0.73, p0.001*Hazard ratio (HR)=0.73, p0.001*Survival distribution functionSurvival distribution functionSurvival time (months)Survival time (months)1.001.000.750.750.500.500.250.250 00 05 510101515202025253030TarcevaTarcevaPlaceboPlacebo TarcevaTarceva (n=488)(n=488) Pla

7、ceboPlacebo (n=(n=243243) ) Median survival (months)Median survival (months) 6.76.7 4.74.7 1 1- -year survival (%)year survival (%) 3131 2121 特罗凯显著延长特罗凯显著延长PFSPFS达达21%21%Shepherd FA, et al. N Engl J Med 2005;353:123-132.Shepherd FA, et al. N Engl J Med 2005;353:123-132.*HR and p (*HR and p (log-rank

8、 test) log-rank test) adjusted for stratificationadjusted for stratificationfactors at randomisation and EGFR statusfactors at randomisation and EGFR statusPFS: 21%PFS: 21%PFS: 21%PFS: 21%HR=0.61, p0.001*HR=0.61, p0.001*25%25%10%10%TarcevaTarcevaPlaceboPlaceboSurvival distribution functionSurvival d

9、istribution function1.001.000.750.750.500.500.250.250 00 05 510101515202025253030Progression-free survival time (months)Progression-free survival time (months) TarcevaTarceva (n=488)(n=488) PlaceboPlacebo (n=243)(n=243) Median PFSMedian PFS (wks)(wks) 9.79.7 8.08.0 6 6- -month PFS (%)month PFS (%) 2

10、525 1010 二线治疗的OS与1年生存率*Results are not directly comparable becauseof different patient populations1-year survival rate (%)TarcevaDocetaxelGefitinibPemetrexedMedian OS (months)Median OS(minimum reported value)1-year survival rate(minimum reported value)01234567890510152025303540TarcevaDocetaxelGefiti

11、nibPemetrexed6.731特罗凯：二线治疗与化疗疗效相当结果结果特罗凯特罗凯 (150mg/d)(150mg/d)多西他赛多西他赛 (75mg/m(75mg/m2 2) )培美曲塞培美曲塞 (500mg/m(500mg/m2 2) )有效率有效率 (%)(%)8.98.97.1-8.87.1-8.87.1-9.17.1-9.1中位有效期中位有效期 ( (月月) )7.97.95.3-9.15.3-9.14.64.61 1年有效率年有效率 (%)(%)313130-3730-373030中位生存期中位生存期 ( (月月) )6.76.75.7-7.95.7-7.96.7-8.36.7-

12、8.350%三线0-26%三线0%三线l哪类患者从特罗凯治疗中哪类患者从特罗凯治疗中“获益更多获益更多”？BR21BR21：组织学类型与总生存：组织学类型与总生存HR=0.71 (0.56HR=0.71 (0.56 0.92), p=0.008 0.92), p=0.008腺癌腺癌HR=0.67 (0.50HR=0.67 (0.500.90), p=0.00070.90), p=0.0007鳞癌鳞癌Clark GM et al, J Clin Oncol 2006; 24(Suppl. 1):405s Abs. 7166.Clark GM et al, J Clin Oncol 2006; 2

13、4(Suppl. 1):405s Abs. 7166.Tarceva (n=246)Tarceva (n=246)Median 7.8 monthsMedian 7.8 monthsSurvival distribution functionSurvival distribution function1.001.000.750.750.500.500.250.250 0Time (months)Time (months)0 05 510101515202025253030Placebo (n=119)Placebo (n=119)Median 5.4 monthsMedian 5.4 mont

14、hsTime (months)Time (months)0 05 510101515202025251.001.000.750.750.500.500.250.250 0Placebo (n=78)Placebo (n=78)Median 3.6 monthsMedian 3.6 monthsTarceva (n=144)Tarceva (n=144)Median 5.6 monthsMedian 5.6 months女性、腺癌、不吸烟女性、腺癌、不吸烟OSOS达到达到11.811.8个月个月Median OS Median OS (months)(months)Tarceva (n=50)T

15、arceva (n=50)11.811.8Placebo (n=26)Placebo (n=26)3.93.9HR=0.412HR=0.412(95% CI: 0.234-(95% CI: 0.234-0.724)0.724)Survival (months)Survival (months)Survival probabilitySurvival probability1.001.000.750.750.500.500.250.250 00 06 6121218182424RR=19.0%RR=19.0%OSI Pharmaceuticals and Roche; data on fileO

16、SI Pharmaceuticals and Roche; data on file男性、吸烟、鳞癌也能显著获益男性、吸烟、鳞癌也能显著获益Median OS Median OS (months)(months)Tarceva (n=100)Tarceva (n=100)5.55.5Placebo (n=57)Placebo (n=57)3.43.4Survival distribution functionSurvival distribution function1.001.000.750.750.500.500.250.250 00 02.52.55.05.07.57.510.010.0

17、12.512.515.015.017.517.520.020.0HR=0.66HR=0.66(95% CI: 0.47- 0.92)(95% CI: 0.47- 0.92)Time (months)Time (months)RR=6.8%RR=6.8%Clark GM et al, Clark GM et al, Clin Lung Cancer 2006;7:389-394.Clin Lung Cancer 2006;7:389-394.哪种临床特征患者更能从哪种临床特征患者更能从特罗凯的治疗中获益？特罗凯的治疗中获益？特罗凯 OS (月)安慰剂 OS (月)l特罗凯能延长各种临床特征患者的

18、总生存期特罗凯能延长各种临床特征患者的总生存期“ “女性、腺癌、不吸烟、亚裔女性、腺癌、不吸烟、亚裔” ” 从特罗凯治疗中从特罗凯治疗中“ “获益更多获益更多” ”BR21BR21：皮疹是生存获益的信号：皮疹是生存获益的信号 OS OSWacker B et al, Clin Cancer Res 2007;13 :3913-3921.Wacker B et al, Clin Cancer Res 2007;13 :3913-3921.l不包括在入组不包括在入组2828日内死亡的患者日内死亡的患者l多变量分析中含协同关系多变量分析中含协同关系级别级别HRHR95% CI95% CIp p 值值

19、2+ vs 02+ vs 00.290.290.22-0.380.22-0.380.0010.0011 vs 01 vs 00.410.410.31-0.550.31-0.550.0015050个国家/地区l7,000例IV期临床试验TRUSTMok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.19001.Perng RP et al, Lung Cancer 2008; 62:78-84.Perng RP et al, L

20、ung Cancer 2008; 62:78-84.2008 Data in Press.2008 Data in Press.Uhm JE, et al. J Thorac Oncol. 2009; 4(9):1136-1143.Uhm JE, et al. J Thorac Oncol. 2009; 4(9):1136-1143.Guan ZZ, et al. 2005.Guan ZZ, et al. 2005.Niho et al. 2007.Niho et al. 2007.客观缓解率客观缓解率TRUSTTRUST亚洲亚洲TRUSTTRUST中国中国TRUSTTRUST台湾台湾V-15

21、-32V-15-32JMIDJMID在我国，疗效优于二线化疗Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.19001.Perng RP et al, Lung Cancer 2008; 62:78-84.Perng RP et al, Lung Cancer 2008; 62:78-84.2008 Data in Press.2008 Data in Press.Uhm JE, et al. J Thorac Onco

22、l. 2009; 4(9):1136-1143.Uhm JE, et al. J Thorac Oncol. 2009; 4(9):1136-1143.Guan ZZ, et al. 2005.Guan ZZ, et al. 2005.Niho et al. 2007.Niho et al. 2007.疾病控制率疾病控制率TRUSTTRUST亚洲亚洲TRUSTTRUST中国中国TRUSTTRUST台湾台湾V-15-32V-15-32JMIDJMID在我国，疗效优于二线化疗l TRUST中国亚组：OS长达15.64个月N=518N=518MST (MST (月月): 15.64): 15.649

23、5%CI: 14.72-18.4095%CI: 14.72-18.401YS: 62.5%1YS: 62.5%2008 Data in Press.生存概率时间 (天)中国大陆1.00.50.005001000在我国，疗效优于二线化疗TRUSTTRUST详细详细BR21BR21TRUSTTRUSTl全球化全球化l多中心多中心l随机随机l双盲双盲l安慰剂对照安慰剂对照lIIIIII期期临床研临床研究究l全球化全球化l多中心多中心l非随机非随机l开放开放l无对照无对照lIVIV期期临床研究临床研究从从BR21BR21到到TRUSTTRUST从从严格严格的临床研究到的临床研究到真实真实的临床实践的临

24、床实践1. TRUST1. TRUST在亚洲开展的情况如何？在亚洲开展的情况如何？特罗凯：从特罗凯：从BR21BR21到亚洲经验到亚洲经验Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.N=1223N=1223NSCLCNSCLC在亚洲地区的发病特点在亚洲地区的发病特点Age standardized incidence per 100,000 Age standardized incidence per 1

25、00,000 亚洲男性发病率亚洲男性发病率 欧美欧美欧美欧美Parkin et al, Parkin et al, European Journal of Cancer 2001; 37: S4-European Journal of Cancer 2001; 37: S4-S66.S66.亚洲地区亚洲地区NSCLCNSCLC以腺癌居多以腺癌居多25.225.243.243.234.134.128.328.311.911.93.33.3(%)(%)0 05 51010151520202525303035354040454550501967-19761967-19761991-19991991-

26、1999腺癌腺癌鳞癌鳞癌大细胞癌大细胞癌马来西亚马来西亚Liam CK, et al, Lung Cancer 2006; 53: 23-30.Liam CK, et al, Lung Cancer 2006; 53: 23-30.(n=198)(n=198)(n=439)(n=439)腺癌发病率在男性和女性中均明显增加腺癌发病率在男性和女性中均明显增加肿瘤类型男性(n=196)女性 (n=82)男性(n=427)女性(n=156)年代年代年代年代1967-19761967-19761967-19761967-19761991-19991991-19991991-19991991-1999腺癌

27、23%23%31%31%37%37%60%60%鳞癌36%36%29%29%33%33%17%17%大细胞癌12%12%12%12%4%4%2%2%Liam CK, et al, Lung Cancer 2006; 53: 23-30.Liam CK, et al, Lung Cancer 2006; 53: 23-30.TRUST研究：研究：亚洲组基线特征符合流行病学特征亚洲组基线特征符合流行病学特征Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.基线条件基线条件N=1223(%)年龄年龄 ( (岁岁) )63 (19-9

28、5)男男 / / 女女54 / 46腺癌腺癌 / / 鳞癌鳞癌 / / 其他其他70 / 18 / 12不吸烟不吸烟 / / 曾吸烟曾吸烟55 / 45ECOG PS 0 / 1 / 2 / 316 / 65 / 14 / 4特罗凯特罗凯 1 / 2 / 3 1 / 2 / 3 线线9 / 57 / 342. TRUST2. TRUST全球结果验证了全球结果验证了BR21BR21的结果吗？的结果吗？TRUSTTRUST研究的主要结果研究的主要结果 缓解与稳定缓解与稳定0%0%20%20%40%40%60%60%80%80%100%100%全球全球(n=5567)(n=5567)欧洲欧洲(n=3

29、222)(n=3222)二线二线(n=2780)(n=2780)SDSDRRRR12%12%9%9%14%14%56%56%58%58%54%54%BR21BR21(n=427)(n=427)9%9%35%35%ISELISEL(n=959)(n=959)8%8%32%32%Groen H. et al, Ann Oncol 2008; 8(19): 266P.; Reck M. et al, Ann Oncol 2008; 8(19): 262P.Crino L. et al, Ann Oncol 2008; 8(19): 264P.; Thatcher N, et al. Lancet 2

30、005;366:1527-1537.Shepherd FA, et al. N Engl J Med 2005;353:123-132.; Doulliad et al, presented in 2007 WCLC.DCRDCR68%68%DCRDCR67%67%DCRDCR68%68%INTERESTINTERESTRR: 9.1%(G) Vs. 7.6%(D)RR: 9.1%(G) Vs. 7.6%(D)TRUSTTRUST研究的主要结果研究的主要结果 生存时间生存时间Groen H. et al, Ann Oncol 2008; 8(19): 266P.Reck M. et al, A

31、nn Oncol 2008; 8(19): 262P.Crino L. et al, Ann Oncol 2008; 8(19): 264P.Thatcher N, et al. Lancet 2005;366:1527-1537.Shepherd FA, et al. N Engl J Med 2005;353:123-132.Doulliad et al, presented in 2007 WCLC.1414121239393232313127270 010102020303040405050全球全球欧洲欧洲101012*12*BR21BR21ISELISELPFS (week)PFS

32、(week)1YS (%)1YS (%)* Value for * Value for TTFTTFINTERESTINTERESTPFS: 8.8 (G) Vs. 10.8 (D)PFS: 8.8 (G) Vs. 10.8 (D)1YS: 32% (G) Vs. 34% (D)1YS: 32% (G) Vs. 34% (D)特罗凯特罗凯TRUSTTRUST亚洲结果：亚洲结果：DCR DCR 78%78%Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.Mok TS et al, J Clin Oncol, 2008; 26

33、(Suppl.): abstr 19001.N=1097N=1097(%)(%)特罗凯：亚洲与全球的疗效比较特罗凯：亚洲与全球的疗效比较Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.Reck M. et al, Ann Oncol 2008; 8(19): 262P.Reck M. et al, Ann Oncol 2008; 8(19): 262P.最佳疗效最佳疗效 (%)(%)特罗凯特罗凯TRUSTTR

34、UST亚洲结果：亚洲结果：PFS PFS 25.525.5周周Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.Mok TS et al, J Clin Oncol, 2008; 26 (Suppl.): abstr 19001.N=1223N=1223( (周周) )N=989N=989N=177N=1773. TRUST3. TRUST中国组的研究结果如何？中国组的研究结果如何？TRUSTTRUST中国的研究中心中国的研究中心 (n=518)(n=518)研究中心研究中心研究者研究者* *广广东东省人民医院省人民医院吴一吴

35、一龙龙中山大学附属中山大学附属肿肿瘤医院瘤医院张张力力北京北京协协和医院和医院李李龙龙芸芸浙江省浙江省肿肿瘤医院瘤医院马胜马胜林林中国医学科学院中国医学科学院肿肿瘤医院瘤医院石石远凯远凯上海肺科医院上海肺科医院周彩存周彩存北京北京结结核病防治所核病防治所朱允中朱允中上海胸科医院上海胸科医院廖美琳廖美琳2008 Data in Press.2008 Data in Press.* Sequence is based on recruitment patient number* Sequence is based on recruitment patient number特罗凯中国注册临床：基线特

36、征特罗凯中国注册临床：基线特征 (n=518)(n=518)基线特征基线特征 (n=518)(n=518)%年龄年龄 ( (岁岁) )中位中位 ( (范围范围) )58 (24-85)58 (24-85)性别性别男性男性 / / 女性女性57 / 4357 / 43ECOG ECOG 功能状态功能状态0 / 1 / 2 / 30 / 1 / 2 / 318 / 62 / 16 / 418 / 62 / 16 / 4肿瘤分期肿瘤分期 IIIB / IV IIIB / IV18 / 8118 / 81组织学类型组织学类型腺癌腺癌 / BAC / / BAC / 大细胞癌大细胞癌 / / 鳞癌鳞癌7

37、3 / 4 / 1 / 1873 / 4 / 1 / 18既往化疗既往化疗特罗凯特罗凯 一线一线11特罗凯特罗凯 二线二线5858特罗凯特罗凯 三线三线4242吸烟状态吸烟状态非吸烟非吸烟 / / 曾吸烟曾吸烟54 / 4554 / 452008 Data in Press.2008 Data in Press.特罗凯中国注册临床：最终结果特罗凯中国注册临床：最终结果 (n=518)(n=518)疗效结果疗效结果N=518N=518(%)(%)CRCR3 311PRPR1141142222SDSD2722725353DCRDCRDCRDCR38938938938975757575TRUST T

38、RUST 亚裔亚组亚裔亚组 DCR (%)DCR (%)N=1097N=109778787878TRUST TRUST 台湾亚组台湾亚组 DCR (%)DCR (%)N=299N=299737373732008 Data in Press.2008 Data in Press.特罗凯中国注册临床最终结果：特罗凯中国注册临床最终结果：PFSPFS2008 Data in Press.2008 Data in Press.N=518N=518PFS (PFS (月月): 6.90): 6.9095%CI: 5.65-7.9895%CI: 5.65-7.98特罗凯中国注册临床最终结果：特罗凯中国注册

39、临床最终结果：OSOS2008 Data in Press.2008 Data in Press.N=518N=518OS (OS (月月): 15.64): 15.6495%CI: 14.72-18.4095%CI: 14.72-18.401YS (%): 62.51YS (%): 62.5特罗凯中国注册临床特罗凯中国注册临床：不良反应不良反应不良反应不良反应发发生率生率皮疹皮疹所有级别所有级别87%87%3 3或或4 4度度5%5%特特罗凯罗凯相关不良反相关不良反应应11%11%特特罗凯罗凯相关的相关的严严重不良反重不良反应应1%1%特特罗凯罗凯相关不良反相关不良反应导应导致治致治疗终疗终

40、止止1%1%特特罗凯罗凯相关不良反相关不良反应导应导致死亡致死亡0%0%2008 Data in Press.2008 Data in Press.TRUSTTRUST研究的结论与启示研究的结论与启示l一项全球、多中心、大样本的一项全球、多中心、大样本的IVIV期临床研究期临床研究总共入组了超过总共入组了超过70007000例全球患者例全球患者具有严格的入组标准和排除标准具有严格的入组标准和排除标准l基线特征比其他研究更符合日常临床实践特点基线特征比其他研究更符合日常临床实践特点l研究结果进一步重复和验证了研究结果进一步重复和验证了BR21BR21的研究结果的研究结果l巩固了特罗凯是晚期巩固了

41、特罗凯是晚期NSCLCNSCLC二线标准治疗的地位二线标准治疗的地位TRUSTTRUST研究的结论与启示研究的结论与启示l二线不应仅依据患者的临床特征而排除从特罗凯二线不应仅依据患者的临床特征而排除从特罗凯治疗中获益的可能治疗中获益的可能全球患者中，每全球患者中，每1010人中有近人中有近7 7人获益人获益亚裔患者中，每亚裔患者中，每1010人中有近人中有近8 8人获益人获益不论何种类型的患者，每不论何种类型的患者，每2 2人中有人中有1 1人获益人获益l再次验证了皮疹是疗效和生存的有效预测因子再次验证了皮疹是疗效和生存的有效预测因子l总体耐受性良好，总体耐受性良好，3/43/4度皮疹的发生率

42、低于度皮疹的发生率低于10%10%SATURNSATURN相当一部分患者并没有后续治疗的机会0 0252550507575100100Fidias et al. 2009Fidias et al. 20091010Scagliotti et al. 2008Scagliotti et al. 20089 9Pirker et al. 2008Pirker et al. 20088 8Ciuleanu et al. 2008Ciuleanu et al. 20087 7Park et al. 2007Park et al. 20076 6Barata et al. 2007Barata et a

43、l. 20075 5von Plessen et al. 2006von Plessen et al. 20064 4Brodowicz et al. 2006Brodowicz et al. 20063 3Belani et al. 2003Belani et al. 20032 2Socinski et al. 2002Socinski et al. 20021 1接受二线治疗的患者比例 (%)近期研究显示，约50%的患者一线治疗进展后不能接受二线治疗观察并等待一线治疗疾病迅速恶化无法接受二线治疗为什么要维持治疗？为什么要维持治疗？l 早期进一步治疗l 控制症状l 延缓进展l 延长生存化疗

44、维持治疗研究的结果：生存药物药物NPFS(HR)P值值腺癌腺癌(PFS HR)鳞癌鳞癌(PFS HR)OS(HR)多西他赛多西他赛153NRP0.001 (中位中位PFS)NRNRP=0.0853 (中位中位OS)培美曲塞培美曲塞4410.60P0.000010.511.030.79P=0.012长春瑞滨长春瑞滨(GCOT)1810.77P=0.32NRNR1.08P=0.48吉西他滨吉西他滨(CECOG)2150.7P0.001NRNRP=0.172绝大多数研究中化疗维持治疗仅显著延长绝大多数研究中化疗维持治疗仅显著延长PFS化疗维持治疗研究的结果：毒性药物药物3/4度毒性度毒性治疗组治疗组

45、安慰剂组安慰剂组P值值多西他赛多西他赛中性粒细胞减少中性粒细胞减少28%-培美曲塞培美曲塞中性粒细胞减少中性粒细胞减少乏力乏力3%5%0%1%P0.05P0.05长春瑞滨长春瑞滨白细胞减少白细胞减少感染感染60%22%NRNRNRNR吉西他滨吉西他滨(CECOG)中性粒细胞减少中性粒细胞减少贫血贫血脱发脱发14.9%2.6%4.3%NRNRNRNRNRNR维持治疗在一定程度上增加了血液系统毒性的发生率并影响生维持治疗在一定程度上增加了血液系统毒性的发生率并影响生活质量活质量JMEN：鳞癌和东亚裔亚组显示培美曲塞维持治疗不如安慰剂的趋势Cappuzzo F et al, ASCO 2009; A

46、bstract No:8001.Belani CP et al, ASCO 2009; Abstract CRA:8000.Favors placebo0.00.20.40.60.81.01.21.41.61.8Favors pemetrexed腺癌 (n=328)鳞癌 (n=182)高加索裔 (n=428)东亚裔 (n=154)其他种族 (n=81)0.40.60.81.01.2特罗凯有利安慰剂有利HR腺癌 (n=401)鳞癌 (n=359)高加索裔 (n=744)东亚裔 (n=128)OSPFS培美曲赛维持治疗的主要不利因素l蓄积毒性 l维持化疗过程繁琐l患者不愿意长期持续化疗l亚裔数据不

47、支持试验背景：TALENT研究Gatzemeier, U et al. J Clin Oncol 2007;25:15451552.0102030405060(周)1.00.80.60.40.20生存概率 (%)化疗阶段Log-rank p=0.0453特罗凯+化疗安慰剂+化疗SATURN: a double-blind, randomized, phase III study of maintenance erlotinib versus placebo following non-progression with 1st-line platinum-based chemotherapy i

48、n patients with advanced NSCLCFederico Cappuzzo1, Tudor Ciuleanu2, Lilia Stelmah3, Saulius Cicenas4, Aleksandra Szczesna5, Erzsebet Juhasz6, Emilio Esteban Gonzalez7, Olivier Molinier8, Gaelle Klingelschmitt9, Giuseppe Giaccone10, on behalf of the SATURN investigators F. Cappuzzo. et al, J Clin Onco

49、l 27:7s, 2009 (suppl; abstr 8001) F. Cappuzzo. et al, J Clin Oncol 27:7s, 2009 (suppl; abstr 8001) SATURN:SATURN: 厄洛替尼作为厄洛替尼作为NSCLCNSCLC一线含铂一线含铂双药化疗后未进展患者维持治疗的随机双药化疗后未进展患者维持治疗的随机双盲双盲IIIIII期临床研究期临床研究PFS* in all patients (ITT)1.00.80.60.40.20081624324048566472808896Time (weeks)HR=0.71 (0.620.82)Log-ra

50、nk p1 提示提示gefitinib疗效更好效更好71.2%47.3%1.1%23.5%Mok et al ESMO LBA 2, 2008IPASS：RREGFR wild-typeHR=0.74 (0.521.05)p=0.0924 Exon 19 or 21 mutations100806040200Survival (%)Time (months)06121824Zhu, et al. JCO 2008Improved survival with erlotinib in patients with EGFR mutations (small patient numbers)Clea

51、r trend towards improved survival with erlotinib in patients with wild-type EGFR而特罗凯Median (months)Erlotinib (n=115)7.9Placebo (n=55) 3.3Median (months)Erlotinib (n=15)10.9Placebo (n=19) 8.3HR=0.55 (0.251.19)p=0.1217100806040200Survival (%)Time (months)06121824Interaction p=0.45IIII期临床研究：厄洛替尼在经治的期临床

52、研究：厄洛替尼在经治的EGFREGFR野生型野生型晚期非小细胞肺癌中的疗效晚期非小细胞肺癌中的疗效Okayama Lung Cancer Study Group Trial 0705(OLCSG 0705)Yoshioka H, Hotta K, Kiura K, et al.J Thorac Oncol 2010;5:99104A phase II trial of erlotinib monotherapy in pretreated patients A phase II trial of erlotinib monotherapy in pretreated patients With

53、 Advanced non-small-cell With Advanced non-small-cell lung cancer who do not possess lung cancer who do not possess active active EGFR mutationsEGFR mutations试验设计Yoshioka Y, et al. J Thorac Oncol 2010;5:99104OLCSG 0705 = Okayama Lung Cancer Study Group trial 0705ECOG PS = Eastern Cooperative Oncolog

54、y Group performance status WT = wild-type; TKI = tyrosine-kinase inhibitorPD = progressive disease化疗后进展 (13线化疗失败)确诊为NSCLC病灶可衡量ECOG PS 02EGFR 野生型 (在18, 19, 20， 21均无突变)未经过TKI治疗厄洛替尼 150mg/day(n=30)病情进展或不可耐受的毒副反应l首要研究终点: 客观缓解率 (ORR)l次要研究终点: PFS, OS, 安全性入组患者基线特征年龄年龄 ( (年年) ) 中位年龄中位年龄 ( (年龄范围年龄范围) )67 (35

55、88)67 (3588)n (%)n (%)性别性别 男男女女24 (80)24 (80)6 (20)6 (20)吸烟史吸烟史 既往吸烟既往吸烟现吸烟现吸烟从未吸烟从未吸烟16 (53)16 (53)8 (27) 8 (27) 6 (20)6 (20)ECOG PSECOG PS 0 0 1 1 2 27 (23)7 (23)19 (63)19 (63)4 (13)4 (13)n (%)n (%)肿瘤类型肿瘤类型 腺癌腺癌 鳞癌鳞癌腺鳞癌腺鳞癌未知未知20 (67)20 (67)7 (23)7 (23)1 (3)1 (3)2 (7)2 (7)肿瘤分期肿瘤分期 IIIBIIIBIVIV 术后复发

56、术后复发5 (17)5 (17)14 (47)14 (47)11 (37)11 (37)既往化疗次数既往化疗次数 1 1 2 2 2 214 (47)14 (47)12 (40)12 (40)4 (13)4 (13)Yoshioka Y, et al. J Thorac Oncol 2010;5:99104Yoshioka Y, et al. J Thorac Oncol 2010;5:99104生存获益Time (months)Probability of survivalPFSOS0.10.80.60.40.2002468101214nMedian PFS (months)HR(95% C

57、I)302.11.43.0nMedian OS (months)HR(95% CI)309.27.511.2Time (months)0.10.80.60.40.2002468101214生存获益 lEGFR野生型的患者使用厄洛替尼治疗也能取得9.2个月1的生存获益，与标准化疗相当。多西他赛 7.58 个月24培美曲赛 8.3 个月4l不论肿瘤类型如何，全体入组患者均可得到相应生存获益 (腺癌 8.6个月；其他 10.1 个月)l只有一个患者得到疾病缓解（3%）, 大多数患者疾病稳定 (60%)提示厄洛替尼在EGFR野生型的患者中的生存获益大部分表现为疾病稳定，而非CR、PRSD = stab

58、le disease; adeno. = adenocarcinomaEGFR 野生型患者的不同疗效：厄洛替尼与吉非替尼EGFR野生型的野生型的NSCLC患者患者OLCSG 07051BR.212INTEREST3ISEL3Median OS (months)0246810ErlotinibGefitinib1. Yoshioka Y, et al. J Thorac Oncol 2010;5:99104 2. Zhu C, et al. J Clin Oncol 2008;26:426875; 3. Gefitinib SmPC 2010生存获益与标准化疗相当复发的复发的 NSCLC 患者患

59、者 （综合各试验数据）（综合各试验数据）OLCSG 07051BR.212JMEI3 JMEI3TAX3174INTEREST5厄洛替你厄洛替你培美曲赛培美曲赛多西他赛多西他赛Median OS (months)02468101. Yoshioka Y, et al. J Thorac Oncol 2010;5:99104; 2. Shepherd F, et al. N Engl J Med 2005;353:12332; 3. Hanna N, et al. J Clin Oncol 2004;22:158997; 4. Shepherd F, et al. J Clin Oncol 20

60、00;18:2095103; 5. Kim E, et al. Lancet 2008;372:180918研究结论l第一个前瞻性的评价厄洛替尼在EGFR野生型NSCLC患者中疗效的试验l所有患者取得了可喜的生存获益，与标准化疗相当 OS 9.2 months vs 7.58.3 monthsl与吉非替尼不同，厄洛替尼在EGFR野生型的NSCLC患者中也可以得到明显的生存获益研究结论这是首个特罗凯治疗EGFR野生型肿瘤患者的前瞻性生物标志物研究。研究结果显示：对于EGFR野生型患者特罗凯与标准二线化疗药物多西他赛一样安全和有效 H. Yoshioka . et al, J Clin Oncol

61、 27:7s, 2009 (suppl; abstr 8067) 20102010年年ASCOASCO20102010年年 ASCOASCO最新亮点最新亮点l TORCH TORCH研究研究l OPTIMAL研究l CALGB 30406研究 TORCH研究TKI可否替代含铂双药用于一线？NSCLCIIIB/IVChemo-naive PS 0-1(n=760)Cisplatin 80mg/m2 d1+ Gemcitabine 1200mg/m2 d1,8 q3w (n=380)Erlotinib150mg/d(n=380)PDlPrimary endpoint: OS of first-li

62、ne Erlotinib followed at progression by CG was not inferior than OS of standard first-line CG followed at progression by Erlotinib RCisplatin 80mg/m2 d1+ Gemcitabine 1200mg/m2 d1,8 q3w (n=380)PDErlotinib150mg/d(n=380)TORCH研究结论lOSOS：一线：一线TKITKI组组8.58.5个月个月 vs vs 标准治疗组标准治疗组12.012.0个月个月l化疗序贯化疗序贯TKITKI的

63、标准治疗优于的标准治疗优于TKITKI序贯化疗的策略序贯化疗的策略l在非选择的人群中，仍然应考虑标准治疗在非选择的人群中，仍然应考虑标准治疗OPTIMALOPTIMAL EGFR突变人群，TKI对比化疗Erlotinib 150mg/daylChemonave advanced NSCLClEGFR Act Mut+ (exon 19 deletion or exon 21 L858R mutation) lECOG PS 02 (n=165)Platinum-based doublet chemotherapy:GC*R*Gemcitabine 1,000mg/m2 (d1, 8) plus

64、 carboplatin AUC=5 (day 1); i.v., every 3 weeks, up to 4 cyclesECOG = Eastern Cooperative Oncology Group; PS = performance status CTONG 0802; ML20981 1:1Stratified by mutation type, histology, smoking statusOPTIMALOPTIMAL初步结果初步结果l我国学者组织的针对EGFR突变患者TKI疗效的III期临床研究lEGFR突变阳性的晚期NSCLC一线治疗l厄洛替尼 vs 卡铂吉西他滨l初步

65、结果显示：厄洛替尼一线治疗更易耐受、未发现新的安全性信号l疗效数据将在ESMO 进行报道 CALGB 30406CALGB 30406厄洛替尼和厄洛替尼联合CP方案在治疗不吸烟和轻度吸烟的腺癌病人的II期临床随机研究Randomized phase II trial of erlotinib(E)alone or in combination withcarboplatin/paclitaxel(CP) in never or light former smokers with advanced lung adenocarcinoma:CALGB 30406随机随机随机随机IIIIIIII期研

66、究期研究期研究期研究CALGB 30406 CALGB 30406 CALGB 30406 CALGB 30406 ：实验设计实验设计实验设计实验设计Chemotherapy-naive patients with stage IIIB/IV adenocarcinoma or BAC who are never or “light”former smokers*ECOG PS 0-1Daily oral erlotinib(n=82)Daily oral erlotinib Erlotinib 150mg/dDaily oral erlotinib+ 6 cycles carboplatin

67、/paclitaxel(n=100)Daily oral erlotinibErlotinib 150mg/d Response evaluation every 2cycles(6 weeks). Therapy couldcontinue until disease progression or toxicity*never smoker:100 cigarettes/lifetime; “light” former smoker:quit1 year ago and 10 pack yearsECP: Erlotinib 150mg/d continuously + capboplati

68、n (AUC=6) +paclitaxel 200mg/m2 q3w6cylesProgression Free and Overall SurvivalsProgression Free and Overall Survivals无无进进展生存率和展生存率和总总生存率生存率Progression Free SurvivalOverall SurvivalE (n=81)ECP (n=100)E (n=81)ECP (n=100)Proportion Progression FreeSurvival ProbabilityTime(months)Time(months)Erlotinib: 6

69、.7(4.0-8.3)Erlotinib/CP: 6.6(5.4-8.2)Erlotinib: 24.3(18.4-31.3)Erlotinib/CP: 19.6(14.4-28.7)Response Rate Erlotinib: 35%Erlotinib/CP: 48% OS 12 monthsCALGB 30406CALGB 30406lPatients with advanced NSCLC typically survive for only Patients with advanced NSCLC typically survive for only about 12 months

70、 with chemotherapy alone.about 12 months with chemotherapy alone.晚期病人晚期病人单单用化用化疗疗一一般生存般生存1212个月左右个月左右lOverall people who received Tarceva plus chemotherapy lived Overall people who received Tarceva plus chemotherapy lived a median of a median of 19.6 months19.6 months and those who received Tarceva

71、and those who received Tarceva alone lived a median of alone lived a median of 24.3 months24.3 months (median PFS 6.6 months (median PFS 6.6 months and 6.7 months, respectively).and 6.7 months, respectively).E+CPE+CP中位生存中位生存19.619.6个月，个月，E E中位生中位生存存24.324.3个月。个月。lThe evidence suggests that patients

72、with this distinct type The evidence suggests that patients with this distinct type of lung cancer may gain exceptional survival benefits from of lung cancer may gain exceptional survival benefits from first-line treatment with Tarceva.first-line treatment with Tarceva.临临床床证证明明E E对对有突有突变变病人一病人一线线治治疗

73、疗有效。有效。E and ECP OS by EGFR mutationE and ECP OS by EGFR mutationE and ECP OS by EGFR mutationE and ECP OS by EGFR mutationOverall SurvivalOverall SurvivalTime(months)Time(months)Survival ProbabilitySurvival ProbabilityEGFR mut (n=33)EGFR mut (n=33)EGFR WT (n=54)EGFR WT (n=54)EGFR mutant:EGFR mutant

74、:39.039.0(38.1-NA)(38.1-NA)EGFR WT:13.7(8.7-20.7) EGFR WT:13.7(8.7-20.7) P=0.0012P=0.0012Overall SurvivalOverall SurvivalEGFR mut (n=33)EGFR mut (n=33)EGFR WT (n=44)EGFR WT (n=44)Time(months)Time(months)EGFR mutant: EGFR mutant: 31.331.3(23.8-42.8)(23.8-42.8)EGFR WT: 18.1(9.5-25.0)EGFR WT: 18.1(9.5-

75、25.0)Survival ProbabilitySurvival Probability Tarceva extended survival beyond Tarceva extended survival beyond threethree years for patients diagnosed years for patients diagnosed with advanced NSCLC that had EGFR activating mutations. with advanced NSCLC that had EGFR activating mutations. CALGB 3

76、0406 ConclusionsCALGB 30406 ConclusionslErlotinib and Erlotinib/CP yield similar outcomes in Erlotinib and Erlotinib/CP yield similar outcomes in a predominately Caucasian never smoker population of a predominately Caucasian never smoker population of NSCLC patientsNSCLC patients（E E和和ECPECP治治疗疗白种人不

77、吸烟病人白种人不吸烟病人疗疗效相似）效相似）lEGFR mutations identify patients most likely to EGFR mutations identify patients most likely to benefit (RR, PFS & OS) from E or ECPbenefit (RR, PFS & OS) from E or ECP（基因突（基因突变变在在E E和和ECPECP治治疗疗中可得到受益）中可得到受益）lE is better tolerated than ECPE is better tolerated than ECP（E E比比E

78、CPECP病人有更好的耐病人有更好的耐受性）受性）谢谢 谢！谢！试试 题题特罗凯对比安慰剂的生存期？特罗凯对比安慰剂的生存期？Shepherd FA, et al. N Engl J Med 2005;353:123-132.Shepherd FA, et al. N Engl J Med 2005;353:123-132.*HR and p (*HR and p (log-rank test) log-rank test) adjusted for stratificationadjusted for stratificationfactors at randomisation and EG

79、FR statusfactors at randomisation and EGFR statusOS: 42.5%OS: 42.5%OS: 42.5%OS: 42.5%1YS: 45%1YS: 45%1YS: 45%1YS: 45%Hazard ratio (HR)=0.73, p0.001*Hazard ratio (HR)=0.73, p0.001*Survival distribution functionSurvival distribution functionSurvival time (months)Survival time (months)1.001.000.750.750

80、.500.500.250.250 00 05 510101515202025253030TarcevaTarcevaPlaceboPlacebo TarcevaTarceva (n=488)(n=488) PlaceboPlacebo (n=(n=243243) ) Median survival (months)Median survival (months) 6.76.7 4.74.7 1 1- -year survival (%)year survival (%) 3131 2121 特罗凯和吉非替尼对野生型的有效率分别是特罗凯和吉非替尼对野生型的有效率分别是？n nRR%RR%EGFR

81、EGFR野生型野生型(BR21) (BR21) 特罗凯特罗凯 106 1067.57.5野生型野生型(ISEL)(ISEL) 吉非替尼吉非替尼 116 1162.62.6Tsao M-S, et al. N Engl J Med 2005;353:13344Tsao M-S, et al. N Engl J Med 2005;353:13344Hirsch FR, et al. J Clin Oncol 2006; 24:503442Hirsch FR, et al. J Clin Oncol 2006; 24:503442l为了与一线化疗联用我们进行了哪两个试验？ TALENT和TRIBUT

82、El l TRUST TRUST TRUST TRUST中国亚组：中国亚组：中国亚组：中国亚组：OSOSOSOS长达长达长达长达15.6415.6415.6415.64个月个月个月个月2008 Data in Press.生存概率时间 (天)中国大陆1.00.50.005001000TRUST中国亚组生存期是？特罗凯中国注册临床：最终结果特罗凯中国注册临床：最终结果 (n=518)(n=518)疗效结果疗效结果N=518N=518(%)(%)CRCR3 311PRPR1141142222SDSD2722725353DCRDCRDCRDCR38938938938975757575TRUST TR

83、UST 亚裔亚组亚裔亚组 DCR (%)DCR (%)N=1097N=109778787878TRUST TRUST 台湾亚组台湾亚组 DCR (%)DCR (%)N=299N=299737373732008 Data in Press.2008 Data in Press.特罗凯中国注册特罗凯中国注册临床临床PFSPFS是多少？是多少？2008 Data in Press.2008 Data in Press.N=518N=518PFS (PFS (月月): 6.90): 6.9095%CI: 5.65-7.9895%CI: 5.65-7.98为什么要维持治疗？为什么要维持治疗？l 早期进一

84、步治疗l 控制症状l 延缓进展l 延长生存SATURNSATURN中国亚组无疾病进展期延长了？中国亚组无疾病进展期延长了？1.00.80.60.40.20Probability04812 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100104Time (weeks)63 62 39 28 23 17 13 10544322222211111000059 59 37 31 28 23 19 17 15 15 14 13 13 108643200000000n at riskPlaceboErlotinib11.4

85、17.9PlaceboErlotinibHR=0.57 (0.370.86)Log-rank p=0.0067延缓疾病进展6.5周中位生存期延长了？中位生存期延长了？1.00.80.60.40.20SurvivalTime (months)03691215182124273033366561534642332116111060060575045373526191610310n at riskPlaceboErlotinib15.220.8HR=0.67 (0.421.07)Log-rank p=0.0931PlaceboErlotinib中位OS延长5.6月不是题：不是题：特罗凯维持治疗亚裔特

86、罗凯维持治疗亚裔NSLCCNSLCCl 早期进一步治疗14%SD转PRl 控制症状l 延缓进展6.5周l 延长生存5.6月特罗凯西班牙研究最终结果特罗凯西班牙研究最终结果 (vs. 2008(vs. 2008年报道的结果年报道的结果) )Sirera R et al, Ann Oncol 2008; 8(19): 230PD.Massuti B et al, ASCO 2009; Abstract No: 8023.2009 ASCO(N=217)2008 ESMO(N=165)CR12.2%13.2%RR70.6%73.1%TTP14.0M12.0MOS27.0M24.0MEGFREGFR突

87、变的突变的NSCLCNSCLC患者患者OSOS超过超过2 2年年SWOG9509 / ECOG1594TAX326 / ILCP / JMDB10.37.4FLEX11特罗凯特罗凯西班牙研究西班牙研究EGFR基因突变基因突变270MST (月月)510152025化疗化疗+Avastin12.3TKIsTKIs治疗治疗EGFR EGFR 突变者突变者PFS PFS 显著高于化疗，其中特罗凯显著高于化疗，其中特罗凯PFSPFS高于易瑞沙高于易瑞沙Pooled median PFS (95% accuracy interval)monthsErlotinibGefitinibChemotherap

88、yAny line13.2 (12.014.7)9.8 (9.210.4)5.9 (5.36.5)1st line12.5 (10.016.0)9.9 (9.010.9)6.0 (5.46.7)Paz-Ares et al. wclc 2009对具有活化对具有活化对具有活化对具有活化EGFREGFR突变或基因扩增或不吸烟的突变或基因扩增或不吸烟的突变或基因扩增或不吸烟的突变或基因扩增或不吸烟的晚期、转移性晚期、转移性晚期、转移性晚期、转移性NSCLCNSCLC患者一线治疗采用厄洛患者一线治疗采用厄洛患者一线治疗采用厄洛患者一线治疗采用厄洛替尼替尼替尼替尼+/-+/-化疗。化疗。化疗。化疗。 日

89、本试验：特罗凯治疗日本试验：特罗凯治疗EGFREGFR野生型的野生型的PFSPFS和和OSOS分别是？分别是？Time (months)Probability of survivalPFSOS0.10.80.60.40.2002468101214nMedian PFS (months)HR(95% CI)302.11.43.0nMedian OS (months)HR(95% CI)309.27.511.2Time (months)0.10.80.60.40.2002468101214不是题：不是题：生存生存获益获益 lEGFR野生型的患者使用厄洛替尼治疗也能取得9.2个月1的生存获益，与标准

90、化疗相当。多西他赛 7.58 个月24培美曲赛 8.3 个月4l不论肿瘤类型如何，全体入组患者均可得到相应生存获益 (腺癌 8.6个月；其他 10.1 个月)l只有一个患者得到疾病缓解（3%）, 大多数患者疾病稳定 (60%)提示厄洛替尼在EGFR野生型的患者中的生存获益大部分表现为疾病稳定，而非CR、PRSD = stable disease; adeno. = adenocarcinomaEGFREGFR 野生型患者的不同疗效：野生型患者的不同疗效：厄洛替尼与吉非替尼厄洛替尼与吉非替尼EGFR野生型的野生型的NSCLC患者患者OLCSG 07051BR.212INTEREST3ISEL3M

91、edian OS (months)0246810ErlotinibGefitinib1. Yoshioka Y, et al. J Thorac Oncol 2010;5:99104 2. Zhu C, et al. J Clin Oncol 2008;26:426875; 3. Gefitinib SmPC 2010生存获益与标准化疗相当生存获益与标准化疗相当复发的复发的 NSCLC 患者患者 （综合各试验数据）（综合各试验数据）OLCSG 07051BR.212JMEI3 JMEI3TAX3174INTEREST5厄洛替你厄洛替你培美曲赛培美曲赛多西他赛多西他赛Median OS (mon

92、ths)02468101. Yoshioka Y, et al. J Thorac Oncol 2010;5:99104; 2. Shepherd F, et al. N Engl J Med 2005;353:12332; 3. Hanna N, et al. J Clin Oncol 2004;22:158997; 4. Shepherd F, et al. J Clin Oncol 2000;18:2095103; 5. Kim E, et al. Lancet 2008;372:180918TORCH研究的意义在哪里？NSCLCIIIB/IVChemo-naive PS 0-1(n=7

93、60)Cisplatin 80mg/m2 d1+ Gemcitabine 1200mg/m2 d1,8 q3w (n=380)Erlotinib150mg/d(n=380)PDlPrimary endpoint: OS of first-line Erlotinib followed at progression by CG was not inferior than OS of standard first-line CG followed at progression by Erlotinib RCisplatin 80mg/m2 d1+ Gemcitabine 1200mg/m2 d1,

94、8 q3w (n=380)PDErlotinib150mg/d(n=380)CALGB 30406CALGB 30406厄洛替尼和厄洛替尼联合CP方案在治疗不吸烟和轻度吸烟的腺癌病人的II期临床随机研究Randomized phase II trial of erlotinib(E)alone or in combination withcarboplatin/paclitaxel(CP) in never or light former smokers with advanced lung adenocarcinoma:CALGB 30406Progression Free and Over

95、all SurvivalsProgression Free and Overall Survivals无进展生存率和总生存率无进展生存率和总生存率Progression Free SurvivalOverall SurvivalE (n=81)ECP (n=100)E (n=81)ECP (n=100)Proportion Progression FreeSurvival ProbabilityTime(months)Time(months)Erlotinib: 6.7(4.0-8.3)Erlotinib/CP: 6.6(5.4-8.2)Erlotinib: 24.3(18.4-31.3)Er

96、lotinib/CP: 19.6(14.4-28.7)Response Rate Erlotinib: 35%Erlotinib/CP: 48%E and ECP OS by EGFR mutationE and ECP OS by EGFR mutationE and ECP OS by EGFR mutationE and ECP OS by EGFR mutationOverall SurvivalOverall SurvivalTime(months)Time(months)Survival ProbabilitySurvival ProbabilityEGFR mut (n=33)E

97、GFR mut (n=33)EGFR WT (n=54)EGFR WT (n=54)EGFR mutant:EGFR mutant:39.039.0(38.1-NA)(38.1-NA)EGFR WT:13.7(8.7-20.7) EGFR WT:13.7(8.7-20.7) P=0.0012P=0.0012Overall SurvivalOverall SurvivalEGFR mut (n=33)EGFR mut (n=33)EGFR WT (n=44)EGFR WT (n=44)Time(months)Time(months)EGFR mutant: EGFR mutant: 31.331

98、.3(23.8-42.8)(23.8-42.8)EGFR WT: 18.1(9.5-25.0)EGFR WT: 18.1(9.5-25.0)Survival ProbabilitySurvival Probability Tarceva extended survival beyond Tarceva extended survival beyond threethree years for patients diagnosed years for patients diagnosed with advanced NSCLC that had EGFR activating mutations. with advanced NSCLC that had EGFR activating mutations.