_-ASCO晚期NSCLC治疗进展课件.ppt

,2012ASCO晚期NSCLC治疗进展,2012ASCO晚期NSCLC治疗进展,_-ASCO晚期NSCLC治疗进展课件,美国临床肿瘤学会American Society of Clinical Oncology（ASCO）是全球领先的肿瘤专业学术组织。该组织旗下的近40000名会员遍及全球100多个国家。一年一度的ASCO年会是临床肿瘤领域水平最高的盛会。当年很多重要的研究发现和临床试验成果都会选择在ASCO年会上发布。本次年会于6月1日至5日在美国芝加哥召开。,本届年会由ASCO 2011-2012癌症教育委员会（CancerEducation Committee）和科学计划委员会（Scientific,Program Committee）主办，大会主题是联合起来，征服癌症（Collaborating to conquer cancer）。,2012 ASCO介绍,美国临床肿瘤学会American Society of Cl,2012 ASCO介绍,本届年会包括以下会议专场：教育专场（EducationSessions）、特别专场（Special Sessions）、全体会议（Plenary Session）、口头报告（Oral AbstractSessions）、临床科学论坛（Clinical Science,Symposia）、每日专场亮点（Highlights of the DaySessions）、肿瘤学临床问题专场（Clinical Problems inOncology Sessions）、教授见面会（Meet the ProfessorSessions）、壁报讨论会（Poster Discussion Sessions）和普通壁报专场（General Poster Sessions）。,2012 ASCO介绍本届年会包括以下会议专场：教育专场（E,2012 ASCO 晚期NSCLC治疗进展,靶,向,治,疗,化,疗NSCLC的一线维持治疗,EGFR突变型NSCLC治疗TKI与化疗序贯：FAST ACT II模式二线野生型：TKI vs. 化疗TKI辅助治疗探索PS2患者的化疗,2012 ASCO 晚期NSCLC治疗进展靶向治疗化疗EGF,2012 ASCO 晚期NSCLC治疗进展,靶,向,治,疗,化,疗NSCLC的一线维持治疗,EGFR突变型NSCLC治疗TKI与化疗序贯：FAST ACT II模式二线野生型：TKI vs. 化疗TKI辅助治疗探索PS2患者的化疗,2012 ASCO 晚期NSCLC治疗进展靶向治疗化疗EGF,OPTIMAL 研究设计,特罗凯150mg/天,直至进展,未经化疗IIIB/IV期NSCLC,EGFR基因突变,(外显子 19或21 L858R)ECOG PS 02,N=165,吉西他滨1000mg/m2,(d1,，d8) +卡铂（AUC=5,d1) Q3w, 4周期,R,1:1,分层因子,Act Mut+ = activating 突变s; ECOG = Eastern Cooperative Oncology 组; PS = performance status,HRQoL = health-related quality of life; FACT-L = Functional Assessment of Cancer Therapy-Lung;,LCSS=lung cancer symptom scale, 主要终点：无进展生存(PFS), 次要终点：总生存 (OS), 客观有效率 (ORR), 疾病进展时间, 有效持续时间，, HRQoL (FACT-L,LCSS), 生物标记分析, 突变类型 组织学 吸烟状态疗效评价,每6周,Zhou, et al. ASCO 2012, abstr 7520,OPTIMAL 研究设计特罗凯150mg/天直至进展未经化疗,OS probability,Erlotinib,82,81,73,64,50,40,20,3,0,GC,72,68,60,53,45,39,19,3,0,OPTIMAL：ITT人群的OS结果1.0,0.8,0.4,0.2,0,0Patients at risk,5,10,15,25,30,35,40,20Time (months),n,Events,n (%),Median,(months),95% CI,Erlotinib,82,50 (61),22.69,20.0730.39,GC,72,42 (58),28.85,22.8731.47,Log-rank p=0.6915,HR (95%CI): 1.04(0.691.58)0.6,Zhou, et al. ASCO 2012, abstr 7520,OS probabilityErlotinib8281736,OS probability,0,66,54,48,36,18,60,42,30,24,12,6,1.0,0.60.40.20,p=0.443,Cisplatin/docetaxel,Gefitinib0.8HR=1.19 (0.771.83),WJTOG3405: OS,36,39,Time (months)Mitsudomi T, et al. J Clin Oncol 2012;30 (Suppl. 15 Pt I):485s (Abs. 7521),OS probability0665448361860423,1. Masahiro Fukuoka et al, J Clin Oncol 2011,29:2866-2874; 2. Inoue A et al, ASCO 2011, abstr 7519,3. Tetsuya Mitsudomi et al, Lancet Oncol 2010; 11: 12128; ASCO 2012, abstr 7521; 4. Zhou, et al. Lancet Oncol 2011;,12: 73542， ASCO 2012 abstr 7520 ; 5. Rafael Rosell et al, Lancet Published Online January 26, 2012; ASCO 2012,abstr 7522,近年的同类研究均相似：PFS 均有显著获益，而OS 无显著差异,*IPASS Mut + 亚组结果，其余均入组Mut+ 患者的III期研究。,# 数据尚未成熟，只有40% 死亡事件发生，仅供参考,PFSOSEGFR TKI组化疗组HREGFR TKI组化疗,OS为何无获益？,OS为何无获益？,EGFR TKI组接受后续化疗比例,化疗组接受后续TKI比例,IPASS 1NEJ002 2WJTOG3405 3OPTIMAL 4EURTAC 5,75%64.9%61%52%NA,64.3%98.2%91%71%76%,后续治疗的交叉（cross over）,1. Masahiro Fukuoka et al, J Clin Oncol 2011,29:2866-2874; 2. Inoue A et al, ASCO 2011, abstr 75193. Tetsuya Mitsudomi et al, Lancet Oncol 2010; 11: 12128; ASCO 2012, abstr 7521; 4. Zhou, et al. Lancet Oncol 2011;12: 73542， ASCO 2012 abstr 7520 ; 5. Rafael Rosell et al, Lancet Published Online January 26, 2012, ASCO 2012,abstr 7522,EGFR TKI组化疗组IPASS 175%64.3%,OPTIMAL：两个治疗组的后续治疗,Note: a patient may appear in more than one post-study treatment group,*The median number of 2nd-line chemotherapy cycles in the erlotinib arm was twoPatients participate in other clinical trialsPatients receive treatment in any line,特罗凯组2线治疗比例低于GC组 （61% vs 78%），并且平均化疗周期仅2周期,Zhou, et al. ASCO 2012, abstr 7520,后续治疗, n (%)Erlotinib, n=82GC,OS probability,Patients at risk,Erlotinib arm receiving2nd-line chemo,50,48,42,36,32,17,3,0,GC arm receiving 2nd-line EGFR TKI,46,43,40,34,31,14,3,0,0.80.6,0.4,0.2,0,5,10,15,20,25,30,35,40,Time (months),Events,Erlotinib arm receiving,2nd-line chemotherapy,n50,n (%)25 (50),(months)30.39,95% CI25.10NR,GC arm receiving,2nd-line EGFR TKI0,46,23 (50),31.47,27.17NR,OPTIMAL：预设的交叉治疗患者OS分析结果1.0Log-rank p=0.7955,HR (95%CI): 1.08 (0.611.91)Median,Zhou, et al. ASCO 2012, abstr 7520,OS probabilityPatients at risk,EGFR突变 一线TKK 治疗PFS与OS 关系,PFS（月）OS（月）OS-FPSIPASS9.521.61,OS probability,further treatment (n=25) or who were re-challenged (n=1)EGFR TKI and chemo: patients from the Tarceva arm who switched to chemo (n=43) and patients fromthe GC arm who switched to Tarceva in any line (n=51),Received chemo only* (n=21)Received EGFR TKI only (n=33)Received EGFR TKI and chemo (n=94),vs,p=0.0001,vs,p=0.057,Zhou C, et al. J Clin Oncol2012;30 (Suppl. Pt I): (Abs. 7520),20.6,30.4,Time (months)*Chemo only, no EGFR TKI: includes patients from the GC arm who had no further treatment (n=16) orfurther chemotherapy (n=5)EGFR TKI only, no chemo: patients from the Tarceva arm who are still on treatment (n=7), had no,0,5,10,15,20,25,30,35,40,1.00.8,0.6,Log-rankp0.00010.40.2,0,11.7,OPTIMAL:TKI治疗和化疗均接受过的患者OS最长，只接受化疗的患者OS最短,OS probabilityfurther treatmen,主要终点, PFS,Afatinib 40mg/day, IIIB/IV 期肺腺癌 既往未接受过化疗 EGFR 突变*, ECOG PS 01,R,2:1,(n=345)Cisplatin 75mg/m2 +pemetrexed 500mg/m2 d1, q3wPhase III, open-label, multicentre,次要终点：,OSORRDCRDoR,PK,Tumour shrinkageSafetyHR QoLECOG PS deterioration,*Detected by therascreen EGFR 29,分层因素, EGFR mutation Ethnicity,Yang JC-H, et al. J Clin Oncol 2012;30 (Suppl. 18 Pt II): (Abs. LBA7500),LUX-Lung 3: 研究设计,主要终点 PFSAfatinib 40mg/day II,PFS probability,0.80.6,0,0,3,6,9,12,15,18,21,24,27,p0.00010.40.2,Afatinib (n=204)Cis/pem (n=104)HR=0.47 (0.340.65),13.6,6.9,204,Afatinib,No. at risk,49,75,30,115,169,104,Cis/pem,3,0,6,9,2,0,0,17,62,143,35,10,2,Time (months),Garassino MC, et al. J Clin Oncol 2012;30 (Suppl. 18 Pt II): (Abs. LBA7501),LUX-Lung 3：常见突变组（Del19/L858R）PFS（独立评估）1.0,PFS probability0.8003691215182,Afatinib(n=229),Cis/pem(n=111),%DiarrhoeaRash/acne*Stomatitis/mucositis*ParonychiaDry skinNauseaDecreased appetiteFatigue*VomitingNeutropeniaAnaemia,All95897257291821181713,Grade 314168111131311,Grade 400100000000,All1561502665347423228,Grade 30010043138155,Grade 400000000032,LUX-Lung 3：安全性,Incidence of AEs with 20% difference between treatment groups. No grade 5 AEs*Grouped termGarassino MC, et al. J Clin Oncol 2012;30 (Suppl. 18 Pt II): (Abs. LBA7501),AfatinibCis/pem%AllGrade 3Grad,TKI 一线突变的七个随机研究,Mok et al NEJM 2009, Lee et al WCLC 2009, Mitsudomi et al Lancet Oncology 2010,Maemondo NEJM 2010, Zhou et al WCLC 2011,ASCO 2012,作者研究患者数中位 PFSYang. JCLUX-Lung,_-ASCO晚期NSCLC治疗进展课件,2012 ASCO 晚期NSCLC治疗进展,靶,向,治,疗,化,疗NSCLC的一线维持治疗,EGFR突变型NSCLC治疗TKI与化疗序贯：FAST ACT II模式二线野生型：TKI vs. 化疗TKI辅助治疗探索PS2患者的化疗,2012 ASCO 晚期NSCLC治疗进展靶向治疗化疗EGF,FASTACT-II：特罗凯与化疗在亚洲人群中一线交替治疗的III期研究,吉西他滨 1,250mg/m2 (d1,8)；顺铂 75mg/m2或卡铂 5AUC (d1)；厄洛替尼,150mg/天 (d1528),安慰剂,厄洛替尼150mg/天,既往未治IIIB/IV期NSCLC(n=450),1R1,PD,铂(d1)+ 安慰剂(d15-28),吉西他滨(d 1,8) + 顺铂或卡铂(d1)+ 厄洛替尼(d15-28)q4wks x 6个疗程,PD,治疗,治疗后,筛选,按分期、组织学、吸烟状态和化疗 方案分 研究后(可选)层吉西他滨(d 1,8) + 顺铂或卡,研究 的主要研究者： T Mok; Y-L Wu,q4wks x 6个疗程主要终点：无进展生存期(PFS)2009年4月2010年9月共入组451例患者，其中厄洛替尼组226例，安慰剂组225例NCT00883779,FASTACT-II：特罗凯与化疗在亚洲人群中吉西他滨 1,PFS probability,6.0,7.6,Mok T, et al. J Clin Oncol 2012;30 (Suppl. 15 Pt I):484s (Abs. 7519),0,2,4,6,8,10,12,14,16,18,20,22,24,26,28,ITT人群的PFS1.0,0.80.6,Log-rank p0.00010.40.2,0,Time (months)No. at risk,GC-Tarceva 226GC-Placebo 225,192185,162156,136114,10257,8131,6521,4613,337,234,52,21,11,10,00,GC-Tarceva (n=226)GC-Placebo (n=225)HR=0.57 (0.460.70),PFS probability6.07.6Mok T, et,亚组分析：PFS,HR (95% CI),n,Favours GC-Tarceva,Favours GC-placebo,HR,0.2,0.4,0.6,1.0,0.57 (0.460.70) 451,All,65 yrs65 yrsFemaleMaleECOG PS 0ECOG PS 1Stage IIIBStage IVAdenocarcinomaNon-adenocarcinomaCurrent smokerFormer smokerNever smoker,0.48 (0.380.61)0.94 (0.611.43)0.33 (0.230.47)0.81 (0.631.05)0.72 (0.491.07)0.52 (0.410.66)0.52 (0.261.03)0.57 (0.460.71)0.50 (0.390.64)0.90 (0.601.33)0.80 (0.561.15)0.87 (0.581.31)0.39 (0.280.53),34910217927211833345406342109131101219,Gemcitabine / carboplatin,Gemcitabine / cisplatin,0.67 (0.301.50),35,0.56 (0.450.69),413,Mok T, et al. J Clin Oncol 2012;30 (Suppl. 15 Pt I):484s (Abs. 7519),亚组分析：PFSHR (95% CI)nFavours GC,QoL,0.5,1.1Favours GC-placebo,1.0HR,0.8Favours GC-Tarceva,0.6,HR (95% CI) n0.79 (0.630.99) 451p=0.03640.77 (0.610.96) 451p=0.01810.73 (0.590.90) 451p=0.0035,Time tosymptomaticprogressionTime todeteriorationin TOITime todeteriorationin QoL,TOI = Trial Outcome Index,Mok T, et al. J Clin Oncol 2012;30 (Suppl. 15 Pt I):484s (Abs. 7519),QoL0.51.11.00.80.6HR (95% C,2012 ASCO 晚期NSCLC治疗进展,靶,向,治,疗,化,疗NSCLC的一线维持治疗,EGFR突变型NSCLC治疗TKI与化疗序贯：FAST ACT II模式二线野生型：TKI vs. 化疗TKI辅助治疗探索PS2患者的化疗,2012 ASCO 晚期NSCLC治疗进展靶向治疗化疗EGF,R,TAILOR：比较厄洛替尼与多西紫杉醇二线治疗EGFR野生型NSCLC患者的3期研究（Italy）,厄洛替尼150 mg po,daily, 晚期/复发 接受过含铂双药治疗 EGFR野生型 KRAS状态明确 PS评分 0-2分, 分层因素,中心复发/进展化疗方案（pem vs gem,多西紫杉醇75 mg/m2 iv day 1,21 or35 mg/m2 iv day 1,8,15,281：1随机分组N=174,允许交叉用药,vs vnb）PS评分(0 vs 1 vs 2)主要终点：OS；次要终点：PFSMarina Chiara Garassino,et,al,2012,ASCO,oral abstract session,7501#,RTAILOR：比较厄洛替尼与多西紫杉醇二线治疗厄洛替尼,Docetaxel(n=110),Tarceva(n=109),Median age (range), yearsMale / female, %ECOG PS 0 / 1 / 2, %Current or former smoker / never smoker, %Squamous-cell carcinoma / adenocarcinoma / other, %KRAS Mut+ / KRAS WT, %,67 (3583)66 / 3448 / 46 / 672 / 2821 / 76 / 423 / 77,66 (4081)71 / 2948 / 44 / 882 / 1828 / 63 / 824 / 76,入组患者特征,Garassino MC, et al. J Clin Oncol 2012;30 (Suppl. 18 Pt II): (Abs. LBA7501),DocetaxelTarcevaMedian age (ra,2.7,2.4,Estimated from curves,Tailor次要终点：ITT人群的PFSCalculated values,2.72.4Estimated from curvesTai,Best response,Garassino MC, et al. J Clin Oncol 2012;30 (Suppl. 18 Pt II): (Abs. LBA7501),Docetaxel,(n=94)%,Tarceva,(n=92)%,p,0.002,CRPRSDPD,4.39.627.658.5,02.220.677.2,RR (CR + PR)DCR (CR + PR + SD),13.941.5,2.222.8,0.0040.007,Best responseGarassino MC, et,TAILOR：3/4级不良事件,多西他赛 (n=104),厄洛替尼 (n=107),非血液学毒性,恶心与呕吐 (%)虚弱 (%)脱发 (所有级别) (%)皮肤毒性 (%)腹泻 (%)神经毒性 (%)血液学毒性中性粒细胞减少 (%)发热性中性粒细胞减少 (%)导致剂量调整的治疗相关不良事件 (%),382902827422.1,16214311029.0,Garassino MC, et al. 2012 ASCO Abstract 7501.,TAILOR：3/4级不良事件多西他赛 (n=104)厄洛替,*TTF = time to treatment failure,0.4,0.6 0.8 1.0,1.5 2.0,Favours EGFR TKI,Favours placebo,PFS/TTF,SATURN1BR.212ISEL3*,Favours EGFR TKI,Favours placebo,OS,SATURN4BR.215ISEL3,0.4,0.6 0.8 1.0,1.5 2.0,TAILOR*,INTEREST*1,JMEI2,CR/PR, %,13.9,9.8,8.8,*EGFR WT pts1. Cappuzzo et al. 2009; 2. Roche, data on file; 3. Gefitinib SmPC,1,4. Cappuzzo et al. 2009; 5. Zhu et al. 2008Douillard et al. J Clin Oncol 2010; 2Hanna, et al. J Clin Oncol 2004,多西他赛在野生型患者中的疗效对照,Before Tailor We All KnowTKI在野生型患者中的疗效对照,*TTF = time to treatment failu,特罗凯单药治疗无EGFR突变的并伴有无吸烟,或轻度吸烟史的晚期NSCLC患者的II期临床试验：NEJ006/TCOG0903,A phase II study of erlotinib monotherpay in patientswith previously treated advanced non-small cell lungcancer (NSCLC) without EGFR gene mutation whohave never/light smoking history: NEJ006/TCOG0903.,Yoshiki Ishii, Makoto Maemondo, etc.,General Poster Session,Yoshiki Ishii,et,al,2012,ASCO,General Poster session,7561#,特罗凯单药治疗无EGFR突变的并伴有无吸烟或轻度吸烟史的晚,特罗凯150mg/d,研究设计 已经经历过1-3次化疗的患者,PD或不可接受的毒性, IIIB/IV期NSCLC EGFR无突变 无吸烟史或轻度吸烟史n=46主要终点: ORR次要终点：DCR,OS,安全性,Yoshiki Ishii,et,al,2012,ASCO,General Poster session,7561#,EGFR基因由PNA-LNA PCR clamp 方法检测,特罗凯研究设计PD或不可接 IIIB/IV期NSCLC,疗效,Yoshiki Ishii,et,al,2012,ASCO,General Poster session,7561#,DCR 41.3%,（27.1%-55.5%）,ORR 15.2%,（4.9%-25.5%）,特罗凯对复治不吸烟或轻度吸烟的EGFR野生型患者的客观缓解率达到15%,反应类型患者数及比例 n（%）部分反应（PR）7（15.2）,CTONG0806 研究设计,Advanced/recurrent18-80 Years NSCLC(stage IIIB/IV),EGFR wild-typepreviously received one platinum-based chemotherapy regimen, ECOG PS0 - 2.(N=150),NCT00891579,R,Pemetrexed,Gefitinib, Primary Endpoint:,Progression free survival (PFS), Secondary Endpoint:,Response rate (RR)/Overall survival (OS),PD,PD,EGFR野生型患者的疗效，期待中国的研究,CTONG0806 研究设计Advanced/recurr,2012 ASCO 晚期NSCLC治疗进展,靶,向,治,疗,化,疗NSCLC的一线维持治疗,EGFR突变型NSCLC治疗TKI与化疗序贯：FAST ACT II模式二线野生型：TKI vs. 化疗TKI辅助治疗探索PS2患者的化疗,2012 ASCO 晚期NSCLC治疗进展靶向治疗化疗EGF,EGFR突变患者,术后TKI辅助能否获益？,EGFR突变患者术后TKI辅助能否获益？,SELECT研究: 特罗凯用于EGFR突变+NSCLC术后辅助治疗的多中心II期研究,Joel W. Neal , et al. J Clin Oncol 30, 2012 (suppl; abstr 7010),研究设计,主要研究终点：2年DFS率85%,SELECT研究: 特罗凯用于EGFR突变+Joel W.,Joel W. Neal , et al. J Clin Oncol 30, 2012 (suppl; abstr 7010),SELECT研究结果,Joel W. Neal , et al. J Clin O,2012 ASCO 晚期NSCLC治疗进展,靶,向,治,疗,化,疗NSCLC的一线维持治疗,EGFR突变型NSCLC治疗TKI与化疗序贯：FAST ACT II模式二线野生型：TKI vs. 化疗TKI辅助治疗探索PS2患者的化疗,2012 ASCO 晚期NSCLC治疗进展靶向治疗化疗EGF,比较培美曲塞单药vs培美曲塞联合卡铂治疗,PS 2的晚期 NSCLC的随机III期研究,Lilenbaum R, et al. 2012 ASCO Abstract,7506.,比较培美曲塞单药vs培美曲塞联合卡铂治疗PS 2的晚期 NS,研究设计培美曲塞 500mg/m2,q3w4 (n=102)培美曲塞+卡铂AUC 5q3w4 (n=103),晚期非鳞癌NSCLCECOG PS 2既往未接受化疗足够器官功能N=205,R,分层因素：,分期：IIIB/IV年龄：70岁/70岁体重减轻：5% /5%,统计学设定：,研究期望得到总生存期从单药组的2.9个月延长到联合组的4.3个月,Lilenbaum R, et al. 2012 ASCO Abstract 7506.,患者中14例为鳞癌，另外12例组织学未知,主要终点: OS次要终点：ORR,PFS,安全性,研究设计q3w4 (n=102)晚期非鳞癌NSCLC,研究结果：肿瘤缓解情况,Lilenbaum R, et al. 2012 ASCO Abstract 7506.,培美曲塞 (%),培美曲塞+卡铂 (%),CRPRSDPDORR (CR+PR),010.542.647.110.5,2.521.560.815.224.0*,培美曲塞组33.3%的患者，培美曲塞联合卡铂组23.3% 的患者无法评估疗效,*P0.029,研究结果：肿瘤缓解情况Lilenbaum R, et al.,PFS,研究结果：PFS,Lilenbaum R, et al. 2012 ASCO Abstract 7506.,时间 (月),0,6,12,18,24,1.00.80.60.40.20,30,培美曲塞 (n=102)：中位3.0个月培美曲塞+卡铂 (n=103)：中位5.9个月HR=0.4695%CI=0.34-0.63P0.001,PFS研究结果：PFSLilenbaum R, et al.,OS,研究结果：OS,Lilenbaum R, et al. 2012 ASCO Abstract 7506.,时间 (月),培美曲塞 (n=102)：中位5.6个月培美曲塞+卡铂 (n=103)：中位9.1个月HR=0.5795%CI=0.41-0.79P=0.001,0,5,12,18,24,30,1.00.80.60.40.20,36,OS研究结果：OSLilenbaum R, et al. 2,OS,PFS,研究结果：排除鳞癌/未知患者后的生存情况,Lilenbaum R, et al. 2012 ASCO Abstract 7506.,0.60.40.20,0,6,12,18,24,1.00.8,30,0.60.40.20,0,6,12,18,24,1.00.8,30,36,时间 (月),培美曲塞 ：中位3.0个月培美曲塞+卡铂：中位6.3个月HR=0.4595%CI=0.33-0.63,P0.001,培美曲塞 ：中位5.8个月培美曲塞+卡铂：中位9.3个月HR=0.5995%CI=0.42-0.84,P=0.003,时间 (月),PFS,OS,OSPFS研究结果：排除鳞癌/未知患者后的生存情况Lilen,OS,OS,研究结果：老年与不吸烟患者的OS,Lilenbaum R, et al. 2012 ASCO Abstract 7506.,时间 (月),培美曲塞 ：中位6.1个月培美曲塞+卡铂：中位8.3个月HR=0.49,培美曲塞 ：中位5.2个月培美曲塞+卡铂：中位9.4个月HR=0.47,时间 (月),95%CI=0.28-0.87P0.015老年亚组,95%CI=0.23-0.95P0.035不吸烟亚组,0.60.40.20,0,6,12,18,24,1.00.8,30,36,0.60.40.20,0,6,12,18,24,1.00.8,30,36,OSOS研究结果：老年与不吸烟患者的OSLilenbaum,研究结果：不良反应,Lilenbaum R, et al. 2012 ASCO Abstract 7506.,培美曲塞3.901.02.90210.80,培美曲塞+卡铂11.71.05.81.92.915.83.9*,3/4级毒性 (%)贫血 (P=0.066)血小板减少中性粒细胞减少 (P=0.119)发热性中性粒细胞减少(P=0.683)恶心/呕吐腹泻呼吸困难5级事件 (P=0.121)* 肾衰竭；脓毒症；肺炎与血小板减少,研究结果：不良反应Lilenbaum R, et al. 2,2012 ASCO 晚期NSCLC治疗进展,靶,向,治,疗,化,疗NSCLC的一线维持治疗,EGFR突变型NSCLC治疗TKI与化疗序贯：FAST ACT II模式二线野生型：TKI vs. 化疗TKI辅助治疗探索PS2患者的化疗,2012 ASCO 晚期NSCLC治疗进展靶向治疗化疗EGF,IIIB/IV期NSCLC,病理检测为非鳞癌N=939PS 0-1一线接受4个周期培美曲塞联合顺铂双药化疗方案,2:1,培美曲塞+BSC,(n=359)安慰剂+BSC(n=180),随机PS=0-1N=539,DCR,PD,主要终点： PFS,次要终点： ORR OS Safety,分层因素： PS（0 vs 1） IIIB vs IV CR/PR vs SDLuis ,et,al,2012,ASCO,oral abstract session,7507#,PARAMOUNT研究:一线顺铂/培美诱导后, 培美vs安慰剂维持治疗,IIIB/IV期NSCLC病理检测为非鳞癌2:1培美曲塞,OS,PARAMOUNT：自随机起的OS,HR=0.7895%CI=0.64-0.96P=0.0195,1.00.8,0.20.0,0,6,12,18,24,30,36,培美曲塞 (n=359)：中位OS13.9个月安慰剂 (n=180)：中位OS 11.0个月1年生存率：58% vs. 45%,2年生存率：32% vs. 21%0.60.4,时间 (月),Paz-Ares L, et al. 2012 ASCO Abstract LBA7507.,OSPARAMOUNT：自随机起的OSHR=0.781.00,OS,PARAMOUNT：自诱导治疗起的OS,1.0,0.20.0,0,6,12,18,24,30,36,培美曲塞 (n=359)：中位OS 16.9个月,安慰剂 (n-180)：中位OS 14.0个月0.80.60.4,时间 (月),HR=0.7895%CI=0.64-0.96P=0