《肺癌的内科治疗》PPT课件

1、 呼吸病区：王呼吸病区：王 洁洁 肺癌内科治疗进展肺癌内科治疗进展1;.非小细胞肺癌非小细胞肺癌内科治疗研究进展内科治疗研究进展2;.3;.肺癌的分子异常肺癌的分子异常常见的基因改变常见的基因改变烟草烟草对细胞外信号异常应答对细胞外信号异常应答细胞周期失控细胞周期失控凋亡机制失控凋亡机制失控接触抑制丧失接触抑制丧失获得转移能力获得转移能力血管生成血管生成永生化永生化自分泌生长自分泌生长肺泡不典型增生肺泡不典型增生癌前腺瘤癌前腺瘤肺癌肺癌原位癌原位癌异型性变异型性变支气管化生支气管化生正常上皮正常上皮4;.2005 Estimated US Cancer Deaths*ONS=Other ner

2、vous system.Source: American Cancer Society, 2005.Men295,280Women275,0005;.高龄肺癌发病概况高龄肺癌发病概况6;.鳞癌鳞癌 (30%)(30%)男性最常见男性最常见主要与吸烟相关（剂量相关）主要与吸烟相关（剂量相关）局部播散倾向局部播散倾向痰中较易检出痰中较易检出高表达具有解毒和抗氧化特性的基因编高表达具有解毒和抗氧化特性的基因编码蛋白码蛋白非小细胞肺癌非小细胞肺癌(NSCLC)病理类型病理类型腺癌腺癌 (30-50%) 在女性和不吸烟者中最常见的肺癌类型在女性和不吸烟者中最常见的肺癌类型 病变常发于外周病变常发于外周

3、全世界发病率上升全世界发病率上升 高表达与小气道与免疫相关的基因编码高表达与小气道与免疫相关的基因编码蛋白蛋白 K-ras 突变常见突变常见 支气管肺泡癌是其一个亚型支气管肺泡癌是其一个亚型大细胞肺癌大细胞肺癌 (10-25%) 原始的、未分化细胞原始的、未分化细胞 病变常发于外周病变常发于外周l 高度转移倾向高度转移倾向7;.NSCLC 分期分期淋巴结淋巴结主支气管主支气管对侧淋巴结对侧淋巴结远处器官转移远处器官转移胸壁侵犯胸壁侵犯 IV 期期 0 期期 IA 期期 IIB 期期 IIIB 期期8;. NSCLC: NSCLC: 分期及生存分期及生存Mountain. Chest. 1997

4、;1710-1717.Stage I Stage II Stage III Stage IV020406080100Percent survivorsStage at DiagnosisSt ISt IISt IIIASt IIIBSt IV9;.肺癌肺癌内科治疗研究进展内科治疗研究进展10;.11;.NSCLC：复发形式复发形式12;.背景背景13;.IALTIALT临床研究设计临床研究设计RChemotherapyControl Thoracic Radiotherapy 60 Gy*optional, but predefined by N stage at each center 完全

5、切除完全切除 NSCLC NSCLC ASCO, Chicago, June 2, 200314;. 化疗方案化疗方案15;. 结结 果果化疗化疗对照对照 N 932935 中位生存期中位生存期50.8 months44.4 months 中位无病生存期中位无病生存期40.2 months30.5 months 5-年生存率年生存率44.5 %40.4 % 5-年年无病生存率无病生存率39.4 %34.3 %16;.0%20%40%60%80%100%012345HR= 0.86 0.76-0.98 p0.03总生存期总生存期ControlChemotherapy Years164286432

6、602774935181308450624775932At risk 17;.0%20%40%60%80%100%012345HR= 0.83 0.74-0.94 p0.003无病生存无病生存ControlChemotherapy Years141244365505655935158272397544684932At risk 18;. 总总 结结 5年总生存率提高年总生存率提高4.1% （ 40.4% Vs 44.5%） p0.03 5年无病生存提高年无病生存提高5.1 % ( 34.3% VS 39.4%，p0.003) 致死性毒性致死性毒性 0.8% 19;.Correlation be

7、tween stage and activity of Chemotherapy- positive - negative- not tested20;.ASCO 2003 IALT (Le havalier)ASCO 2003JLCRG (Kato)ASCO 2004JBR 10 (Winton)ASCO 2004CALGB (Strauss)21;.有待解决的问题有待解决的问题22;.选择哪些患者？选择哪些患者？23;.化疗的时机？化疗的时机？化疗周期？化疗周期？24;. 新辅助治疗新辅助治疗25;.NSurvivalmedian(mo)2-ys%Rosell*Chemo+Surg3026

8、32Surg Alone3080Roth*Chemo+Surg286460Surg Alone321125*NEJM,1994 *JNCI86;199426;.新辅助治疗新辅助治疗：SWOG 9900 泰素泰素 225 mg/m2卡铂卡铂 AUC = 6X 3 cycles 手术手术RANDOMIZE手术手术Stage IB, II and IIIA (T3N1) N= 374/600Primary Endpoint: 33% improvement in the expected 2.7 medians survival for surgery alonePisters K, et alAS

9、CO Abstract # 7012:27;.无疾病进展生存期无疾病进展生存期HR=0.80 0.59-1.07, p=0.140%20%40%60%80%100%01224364860Months After RegistrationMedian1 yr2 yrPreop31 mo69%55%Control20 mo68%46%median F/U 31 mo SWOG 990028;.总生存总生存 HR=0.84 0.60-1.18, p=0.320%20%40%60%80%100%01224364860Months After Registration SWOG 9900Median1

10、yr2 yrPreop47 mo82%69% Control40 mo79%63%Median FU 31 months29;.Cisplatin, 50 mg/m2 IVPB d1, 8, 29, 36Etoposide, 50 mg/m2 IVPB d1-5, 29-33Thoracic RT, 45 Gy (1.8 Gy/d), begin d1疾病无进展者疾病无进展者 手术手术继续放疗至继续放疗至 61 Gy61 Gy 巩固化疗巩固化疗cisplatin plus etoposideX 2 cycles诱导治疗诱导治疗Albain KS et al30;.CT/RT/S 145/202

11、CT/RT 155/194Logrank p = 0.24Hazard ratio = 0.87 (0.70, 1.10)% Alive0255075100Months from Randomization01224364860Dead/Total Overall SurvivalMedian FU 81 months31;. Overall Survival by Pathologic Nodal StatusNo surgery (n=38)Pathologic N0 (n=76)Pathologic N1-3, unknown (n=88)p 0.0001% Alive025507510

12、0Months from Randomization02040608010012032;. 肺叶切除的总生存肺叶切除的总生存Subset VS Matched CT/RT Subset % Alive0255075100Months from Randomization01224364860/ / / / / / / / /logrank p = 0.002CT/RT/S 57/90CT/RT 74/90Dead/TotalMS 34 mos. 22 mos.5 yr OS 36% 18%CT/RT/S CT/RT33;.Months from Randomization全肺切除的总生存全肺切

13、除的总生存Subset VS Matched CT/RT Subset MS3 yr OS5 yr OS19 mos. 36% 22%CT/RT/SCT/RT% Alive025507510001224364860/29 mos. 45% 24%Dead/TotalCT/RT/S38/51CT/RT42/51logrank p = NS34;.N2 病人是否外科治疗需肺癌多学科讨论决定病人是否外科治疗需肺癌多学科讨论决定 35;.36;.2005 NCCN2005 NCCN临床肿瘤指南临床肿瘤指南多学科治疗：辅助化疗多学科治疗：辅助化疗37;.2005 NCCN2005 NCCN临床肿瘤指南临

14、床肿瘤指南多学科治疗：辅助化疗多学科治疗：辅助化疗38;.术后辅助化疗术后辅助化疗39;.肺癌肺癌内科治疗研究进展内科治疗研究进展40;. 不能手术局部晚期不能手术局部晚期NSCLCNSCLC化放疗结合的方式化放疗结合的方式41;. LAMP: Randomized Phase II Study of 3 Chemoradiation Schedules for Stage III NSCLC 42;.LAMP: Pre-Treatment Characteristics43;.T/CRT Historical 1 yr 59% 58%2 yr 31% 31%Median 13.0 mo 14

15、.5T/CT/C/RT Historical 1 yr 53% 58% 2 yr 22% 31%Median 12.8mo 14.5mo _-T/C/RTT/C Historical 1 yr 64% 58%2 yr 33% 31%Median 16.1mo 14.5mo_-Arm 1Arm 3Arm 244;. SWOG 9504: TreatmentConcurrent ChemoradiationPE:Cisplatin 50 mg/m2 IV d 1, 8, 29, 36Etoposide 50 mg/m2 IV d 1-5, 29-33RT:45 Gy (1.8 Gy/fractio

16、n)16 Gy boost (2 Gy/fraction)ConsolidationDocetaxel 75 mg/m2 IV X 1 cycleDocetaxel 75-100 mg/m2 IV X 2 cycles(every 3 weeks)Gaspar LE, et al. Proc Am Soc Clin Oncol 2001;20:315a. (abstr & poster 1255) 45;.Phase II SWOG Trial (S9504): ResultsRadiographic Response N= 83 Complete Response 3 (4%) Pa

17、rtial Response 49 (59%) Overall Response 52 (63%) Stable Disease 23 (28%) Disease Progression 8 (9%) Survival Median27 mos 18 - 43 mos 1-year survival76% 67% - 85% 2-year survival54% 43% - 64% 3-year survival40% 24% - 55%46;.47;.SWOG 9504Overall Survival0%20%40%60%80%012243648Months RegistrationMedi

18、anN in Months83 45 261 Year Survival: 76%2 Year Survival: 54%3 Year Survival: 40%Gaspar: ASCO 200148;. SWOG 9504 (PE/RT TXT) vs SWOG 9019 (PE/RT PE): Patient Characteristics49;. SWOG 9504 (PE/RT TXT) vs SWOG 9019 (PE/RT PE): Survival (median f/u 28 mos)Gaspar LE, et al. Proc Am Soc Clin Oncol 2001;2

19、0:315a. (abstr & poster 1255) 50;.Current Status of Chemoradiotherapy in Stage III NSCLC Adapted from Pisters: ASCO, 2000 * S950451;.2005 NCCN临床肿瘤指南多学科治疗：辅助化疗52;.肺癌肺癌内科治疗研究进展内科治疗研究进展53;. 治疗原则治疗原则54;.联合化疗作为联合化疗作为NSCLCNSCLC的一线治疗的一线治疗55;.Advanced NSCLCUS FDA Approved Therapies56;. NSCLC: 一线化疗一线化疗57

20、;. 治治 疗疗长春瑞滨长春瑞滨 30 mg/m30 mg/m2 2，第第1 1、8 8天天 每每3 3周周 + + 最佳支持治疗最佳支持治疗最佳支持最佳支持治疗治疗 (BSC)紫杉醇紫杉醇 200 mg/m200 mg/m2 2 第第1 1天天 每每3 3周周 + BSC + BSC最佳支持治疗最佳支持治疗泰索帝泰索帝 100 mg/m100 mg/m2 2 第第1 1天天 每每3 3周周 + BSC + BSC最佳支持治疗最佳支持治疗吉西他滨吉西他滨 1000 mg/m 1000 mg/m2 2 第第1 1、8 8和和1515天天 每每4 4周周 + BSC + BSC最佳支持治疗最佳支持

21、治疗58;.1 .00 .80 .60 .40 .2003691 21 51 82 12 4长春瑞滨长春瑞滨最佳支持治疗最佳支持治疗月月概率概率59;.1 .00 .80 .60 .40 .2003691 21 51 82 12 4紫杉醇紫杉醇最佳支持治疗最佳支持治疗月月概率概率60;.1 .00 .80 .60 .40 .2003691 21 51 82 12 4泰索帝泰索帝最佳支持治疗最佳支持治疗月月概率概率61;.1.00.80.60.40.2003691215182124吉西他滨吉西他滨最佳支持治疗最佳支持治疗月月概率概率62;.ECOG 1594: Study DesignStrat

22、ification:uStage: IIIB vs IVuPS: 01 vs 2uWt Loss: 5% vs 5%uCNS Mets: no vs yesArm AArm A: Cisplatin + Paclitaxel: Cisplatin + PaclitaxelPaclitaxel: 135 mg/mPaclitaxel: 135 mg/m2 2/24 h Day 1/24 h Day 1 Cisplatin: 75 mg/m Cisplatin: 75 mg/m2 2 day 2 day 2q3wkq3wkArm DArm D: Carboplatin + Paclitaxel:

23、Carboplatin + PaclitaxelPaclitaxel: 225 mg/mPaclitaxel: 225 mg/m2 2/3 h Day 1/3 h Day 1Carboplatin: AUC 6 Day 1Carboplatin: AUC 6 Day 1Arm CArm C: Cisplatin + Docetaxel: Cisplatin + DocetaxelDocetaxel: 75 mg/mDocetaxel: 75 mg/m2 2 Day 1 Day 1Cisplatin: 75 mg/mCisplatin: 75 mg/m2 2 Day 1 Day 1Arm BAr

24、m B: Cisplatin + Gemcitabine: Cisplatin + GemcitabineGemcitabine: 1000 mg/mGemcitabine: 1000 mg/m2 2 Days 1, 8, 15 Days 1, 8, 15Cisplatin: 100 mg/mCisplatin: 100 mg/m2 2 Day 1 Day 1q4wkq4wkq3wkq3wkq3wkq3wkSchiller JH, et al. Proc ASCO 36th Annual Meeting. 2000;19:abstr 2.Schiller JH, et al. N Engl J

25、 Med. 2002;346:92-98.R RA AN ND DO OMMI IZ ZE E63;.E1594 64;.ECOG 1594:Analysis of ToxicityECOG 1594:Analysis of Toxicity222266667 7626211115656272728280 010102020303040405050606070703 3 级级4 4 级级%泰素泰素/顺铂顺铂吉西他滨吉西他滨/顺顺铂铂多西紫杉多西紫杉醇醇/顺铂顺铂泰素泰素/卡铂卡铂PS2的病人的的病人的3-4级毒性发生百分比级毒性发生百分比65;. TAX326 Study Design （泰素

26、蒂铂类泰素蒂铂类Vs NVB+Vs NVB+铂类铂类）RANDOMIZEResponse assessment every 2 cycles泰素蒂泰素蒂 75mg/m2 IV 卡铂卡铂 AUC 6 IV Q 3 wks(TCb)诺维苯诺维苯 25mg/m2 IV D 1, 8, 15 & 22顺铂顺铂 100mg/m2 IV D 1Q 4 wks(VC)泰素蒂泰素蒂 75mg/m2 IV顺铂顺铂 75mg/m2 IV Q 3 wks（TC）vs.or66;. TAX 326 Overall SurvivalFossella et al. J Clin.Oncol. 2003;21:30

27、16-3024.100806040200Survival (%)0369 121518 21 24 27 3033Time (months)TCVC100806040200Survival (%)0369 12 1518 21 24 27 3033Time (months)P = .657, adjustedlog-rank testTCbVC1-y survival 46% vs 41% with VC2-y survival 21% vs 14% with VCMedian survival: 11.3 vs 10.1 moP = .044, adjusted log-rank test1

28、-y survival 38% vs 40% with VC2-y survival 18% vs 14% with VC67;.RANDOMIZEProtocol SchemaStratification Weight loss in previous 6 months: 5% vs 5% Disease stage: IIIB with effusion, IV Brain metastases: Presence or absenceGemcitabine 1000 mg/m2 d 1,8Paclitaxel 200 mg/m2 d 1q 21 daysGemcitabine 1000

29、mg/m2 d 1,8Carboplatin AUC 5.5 d 1q 21 daysArm A: 健择健择 + 卡铂卡铂Arm B: 健择健择+ 泰素泰素Arm C: 泰素泰素+ 卡铂卡铂Paclitaxel 225 mg/m2 d 1Carboplatin AUC 6.0 d 1q 21 days68;.Survival by Treatment Arm69;.90年代新化疗药物联合作为非铂方案年代新化疗药物联合作为非铂方案 (N = 3,307)dAddario et al. J Clin Oncol. 2005;23:2926-2936.70;.卡铂卡铂Vs顺铂顺铂71;.NSCLC:

30、 90NSCLC: 90年代新化疗药物顺铂或卡铂的随机研究年代新化疗药物顺铂或卡铂的随机研究 N Zojwalla, 200472;. NSCLC: 9090年代新化疗药物顺铂或卡铂的随机研究年代新化疗药物顺铂或卡铂的随机研究 N Zojwalla, 2004MONTHS Carboplatin Cisplatin N = 1152 N = 11548.79.8* No other such trials 1992 2003; * 2 trials with paclitaxel, 1 with docetaxel, 2 with gem. 73;.Copyright American Soc

31、iety of Clinical OncologyCarbo vs. Cis Meta-analysisOverall survival with cisplatin-based compared with carboplatin-based chemotherapyHotta, K. et al. J Clin Oncol; 22:3852-3859 200474;.Copyright American Society of Clinical OncologyCarbo vs. Cis Meta-analysisOverall survival with cisplatin plus new

32、 agents compared with carboplatin plus new agentsHotta, K. et al. J Clin Oncol; 22:3852-3859 200475;.一线化疗一线化疗: : 怎样选择最好的联合方案怎样选择最好的联合方案? ? 疗效与生存疗效与生存? ? 生活质量生活质量? ? 毒性毒性? ? 病人的基础状态病人的基础状态? ? 费用费用? ?76;.Weekly Paclitaxel with Carboplatin Followed by Maintenance Paclitaxel vs.Observation for Advanced

33、NSCLC Belani et al, JCO 21:2933-39, 2003*Patients with CR, PR or SD randomized to paclitaxel 70 mg/m2/wk or observation77;. Weekly Paclitaxel with Carboplatin Followed by Maintenance Paclitaxel vs.Observation for Advanced NSCLCEfficacy/Toxicity Arm 1 Arm 2 Arm 3Median Survival Time 49 wks 31 wks 40

34、wks (p=0.077 vs 1) (p0.45 vs 1) Median TTP 30 wks 21 wks 27 wks (p=0.01 vs 1) (p0.73 vs 1) 1-yr. Survival 47% 31% 41% (p0.01 vs 1) (p0.20 vs 1) Neutropenia grade 4 22% 8% 19%Thrombocytopenia grade 4 5% 2% 1%Neuropathy grade 3 5% 3% 13% Belani et al, JCO 21:2933-39, 200378;.STRATIFYECOG PS0&1 vs

35、2StageIIIB vs IVRANDOMIZEWeeklyPaclitaxel 100 mg/m2/week x 3Carboplatin AUC=6 (Cycle duration 4 weeks, Total 4 cycles)StandardPaclitaxel 225 mg/m2 3Carboplatin AUC= 6 day 1 (Cycle duration 3 weeks, Total 4 cycles)TAXMEN 12 : Phase III Study Schema*Maintenance Therapy Paclitaxel 70 mg/m2/week 3 weeks

36、 on, 1 week off Until Disease Progression* For patients with CR/PR or SD on both arms79;.Taxmen 12: Kaplan-Meier Estimates Patient Survival1.00.90.80.70.60.50.40.30.20.10.00816 24 32 40 48 56 64 72 80 88 96 104 112120128136144152160WeeklyStandardProportion of Patients Who SurvivedTime (Weeks)80;.81;

37、.82;. Metastatic Lung Cancer83;.FDA FDA 批准的批准的NSCLCNSCLC二线治疗药物二线治疗药物DocetaxelPemetrexedErlotinib84;.NSCLC 二线治疗：泰素蒂二线治疗：泰素蒂 Vs BSC Shepherd et al 2000中位生存期中位生存期(月月)1年年 生存率生存率(%)Log rank: p=0.01泰素蒂泰素蒂 75 mg/m2 (n=55)最好的支持治疗最好的支持治疗 (n=49)036912151821累计的概率累计的概率0.00.20.40.60.81.0泰素蒂泰素蒂75 mg/m27.537最好的支持治

38、最好的支持治疗疗4.612月月85;.% Pemetrexed n = 265 泰索帝 n = 276 泰索帝 N=100(Q3 week) N=98 (weekly) ALT 升高 2 0 N/A 虚弱 5 5 N/A N/A Grade3/4 中性粒细胞减少 5 40 8.8 2.3 粒缺性发热 2 13 1.1 1.1 Grade 3/4 贫血 4 4 3.3 5.7 Grade 3/4 血小板减少 2 2 (IDEAL 2)previouschemotherapyregimensContinue gefitinib until diseaseprogression or unaccep

39、table toxicityPrimary endpointsPatientsl Response rate (both trials)l Safety profile (IDEAL 1)l Symptom relief (IDEAL 2)IDEAL 1 global trial including Japan, Europe, Australia, and South Africa (JPN=209)IDEAL 2 USA trialNatale & Zaretsky 2002 RANDOMIZEDD92;.Gefitinib (Iressa)Gefitinib (Iressa)治疗

40、晚期治疗晚期NSCLCNSCLC的研究的研究( (IDEAL-1,2)IDEAL-1,2)93;.GefitinibGefitinib作为三线药物治疗作为三线药物治疗晚期晚期NSCLCNSCLC的研究的研究Semin Oncol. 2003;30(1 Suppl 1):30-85154疾病控制率疾病控制率()1918有效率（）有效率（）500mg/d250mg/dIDEAL-1N2103543症状改善率症状改善率()912有效率（）有效率（）500mg/d250mg/dIDEAL- 2N21694;.GefitinibGefitinib作为三线药物治疗作为三线药物治疗晚期晚期NSCLCNSCL

41、C的的期研究期研究Oncologist. 2003;8(4):303-6. 7.04.58.9中位有效期(月)10.67.913.6有效率（）两组合并(n=142)500mg/d (n=76)250mg/d(n=66)结论：结论：GefitinibGefitinib用于铂类和多西紫杉醇治疗失败的晚期用于铂类和多西紫杉醇治疗失败的晚期NSCLCNSCLC病人，推荐结论是病人，推荐结论是250250mg/dmg/d。因为因为500500mg/dmg/d的疗效无增加，但毒性更大。的疗效无增加，但毒性更大。95;.ISEL:IRESSA survival evaluation in lung canc

42、er (Trial 709)96;.ISEL：Bankground97;.IRESSA(250 mg/day) 1 end-pointSurvival2 end-pointsTTFORRQoL, symptomsSafetyExploratory end-pointTumour biomarker analysis (eg EGFR)Placebo + BSCCT, chemotherapy; BSC, best supportive care; EGFR, epidermal growth factor receptor; TTF, time to treatment failure; OR

43、R, objective response rate; QoL, quality of lifePatientsLocally advanced or metastatic NSCLC1 or 2 prior CT regimensIntolerant to most recent CT regimen or progression 90 days of last CT cycleISEL trial design98;.0246810121416Time (months)At risk:1692134787748525210431Median, months1-year survival,

44、%Logrank HR (95% CI), 0.89 (0.77, 1.02); p=0.087Cox regression analysis, p=0.030IRESSA5.627Placebo5.1210.00.20.40.60.81.0ProportionsurvivingIRESSAPlaceboCI, confidence interval; HR, hazard ratioMedian follow-up: 7 months (range 315); 58% deathsISEL: survival in the overall population99;.Median, mont

45、hs1-year survival, %Logrank HR (95% CI), 0.84 (0.68, 1.03); p=0.089Cox regression analysis, p=0.033IRESSA6.330Placebo5.418Time (months)At risk:81266944626214566181IRESSAPlacebo02468101214160.00.20.40.60.81.0ProportionsurvivingISEL: Survival in the Adenocarcinoma Population100;.169210515392781294917I

46、RESSAPlaceboIRESSAPlaceboCox analysis (95% CI)LogrankOdds ratio (95% CI)Median TTF, months3.02.60.82 (0.73, 0.92) p=0.0006p=0.002ORR, % (n)8.0 (77/959)1.3 (6/480)7.28 (3.1, 16.9)p0.0001TTF (months)At risk:02468101214160.00.20.40.60.81.0Proportionwithout treatment failureISEL: significant improvement

47、 in TTF and ORR101;.Reasons for treatment failurePatients (%)IRESSAPlacebo6050403020100102;.Overall response rate11%Women18%Men5%Never Smokers29%Current/Former5%SmokersAdenocarcinoma12%Other NSCLC7%103;.Lynch:NEJM2004104;. GGCGGGCCAAACTGCTGGGTGCG 100Selection of Patients for EGFR Inhibitors105;.5/5

48、patients who responded to gefitinib had EGFR mutations 4/4 patients who progressed on gefitinib had no EGFR mutationsPaez: Science Express Rep 2004.CharacteristicAdenocarcinoma Other NSCLCFemale MaleJapaneseAmerican% with Mutation (n) 21% (15/70) 2% (1/49)20% (1/45)9% (7/74)26% (15/58)2% (1/61)106;.

49、Is a bath and a shower always better than either alone?107;.108;.ECOG Trial (E4599): rhuMab VEGF (ECOG Trial (E4599): rhuMab VEGF (贝伐单抗贝伐单抗Bevacizumab) Bevacizumab) 在晚期在晚期NSCLC (Non-Squamous)NSCLC (Non-Squamous)Sample size of 842 patients for 80% power to detect a 25% improvement in median survival ( 8 to 10 mos.)109;.病人特点病人特点 (el