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1、贝伐单抗治疗卵巢癌III期临床实验,R.A. Burger,1 M.F. Brady,2 M.A. Bookman,3 R.A. Burger,1 M.F. Brady,2 M.A. Bookman,3 J.L. Walker,4 H.D. Homesley,5 J. Fowler,6 B.J. Monk,7 B.E. Greer,8 M. Boente,9 S.X. Liang101Fox Chase Cancer Center, Philadelphia, PA; 2Gynecologic Oncology Group Statistical and Data Center, Roswel
2、l Park Cancer Institute, Buffalo, NY; 3University of Arizona Cancer Center, Tucson, AZ; 4University of Oklahoma Health Sciences Center, Oklahoma City, OK; 5Brody School of Medicine, Greenville, NC; 6James Cancer Hospital at the Ohio State University, Hilliard, OH; 7University of California, Irvine M
3、edical Center, Orange, CA; 8Seattle Cancer Care Alliance, Seattle, WA; 9Minnesota Oncology and Hematology, Minneapolis, MN; 10State University of New York at Stony Brook, Stony Brook, NY, USA,贝伐单抗为人源化单克隆IgG1抗体 主要作用靶点为抑制VEGF活性 2004年FDA批准上市用于结直肠癌 2007年Burger et al和Cannistra et al.在J Clin Oncol上分别报道贝伐单
4、抗单抗治疗复发卵巢癌II期临床实验取得较好效果 2009年NCCN把贝伐单抗列为卵巢上皮性癌二线治疗內容,研究的目的：贝伐单抗联合线化疗方案做为初始治疗方案治疗卵巢上皮癌,腹膜癌和输卵管是否能可行？,4,GOG-0218: Schema,Front-line: Epithelial OV, PP or FT cancerStage III optimal (macroscopic)Stage III suboptimalStage IVn=1800 (planned),主要观察点,研究与对照组：PFSOverall survival (OS)safetyquality of lifecorre
5、lative laboratory studies,入组条件,Histologic diagnosis of epithelial OV, PP, or FT cancer Following maximal debulking surgery: stage III optimal (macroscopic residual disease 1 cm) or suboptimal (1 cm), or stage IV No prior chemotherapy 112 weeks after initial surgery GOG PS 02 No history of significan
6、t vascular events No evidence of intestinal obstruction requiring parenteral support Written informed consent,入选病人情况,入选病人情况,随访观察模式,Months,CP + placebo/BEV (6 cycles),Maintenance placebo/BEV (16 cycles),Imaginga,CA-125,Exam,9,aConventional CT or MRI,0 3 6 9 12 15,Same intervals for all modalities: Ev
7、ery 3 months for 2 years, then every 6 months for 3 years, then annually,Post-treatment follow-up,GOG-0218结果分析: PFS,10,CP (Arm I),+ BEV (Arm II),Proportion surviving progression free,Months since randomization,1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0,0 12 24 36,11,分层分析 CP + BEV BEV (Arm III) vs CP
8、(Arm I),Treatment hazard ratio,总生存率分析 At time of final PFS analysis,Proportion alive,Months since randomization,1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0,0 12 24 36 48,12,aStratified analysis,GOG-0218: Mean Patient-Reported TOI Score During Chemotherapy,TOI = Trial Outcome Index of the Functional As
9、sessment of Cancer Therapy-Ovary (FACT-O TOI): FACT-G Physical Well-Being (7 items), Functional Well-Being (7 items) and the Ovarian Cancer Subscale (12 item),112 100 90 80 70 60 50 40 30 20 10 0,Mean TOI score,Randomization,Pre-cycle 4,Pre-cycle 7,CP (Arm I),CP + BEV BEV (Arm III),14,112 100 90 80
10、70 60 50 40 30 20 10 0,GOG-0218:结论,CP + BEV BEV维护方案在PFS优于CP和CP + BEV BEV联合线化疗方案做为初始治疗方案治疗卵巢上皮癌,腹膜癌和输卵管癌患者时病人可以耐受，副反应与BEV单药使用相似 CP + BEV BEV维护方案可考虑用于卵巢上皮癌,腹膜癌和输卵管癌一线治疗,血管生成素抑制剂AMG 386联合紫杉醇周疗方案治疗复发卵巢上皮癌的II期临床研究,Beth Y. Karlan,1 Amit M. Oza,2 Vincent L. Hansen,3 Gary E. Richardson,4 Diane Provencher,5
11、Prafull Ghatage,6 Marjan Tassoudji,7 Daniel E. Stepan,7 David M. Weinreich,7 Ignace B. Vergote8,1Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Princess Margaret Hospital, Toronto, ON, Canada; 3Northern Utah Associates, Ogden, UT, USA; 4Cabrini Hospital, Melbourne, VIC, Australia; 5CHUM-Hpital
12、Notre-Dame, Montreal, QC, Canada; 6Tom Baker Cancer Centre, Calgary, AB, Canada; 7Amgen Inc., Thousand Oaks, CA, USA; 8University Hospital Leuven, European Union.,80%就诊时为晚期卵巢癌的患者将会复发并最终死亡 复发后经治疗，铂类敏感患者平均PFS 9.4-11.3 months，铂类耐药为3.7-4.0 months2,AMG 386为重组的多肽溶合蛋白 临床前动物实验证实AMG 386能抑制移稙的生长 I期临床实验显示有较的耐受
13、性，无明显的毒副反应 其中1例病人用药后一直维持PR伏态达156周以上,研究的目的：,血管生成素抑制剂AMG 386联合紫杉醇周疗方案治疗复发卵巢上皮癌是否影响患者的PFS 其次评价 疗效 安全 药代动力学 机体抗AMG 386抗体的产生,20060342研究设计：,PD,Arm A,AMG 386 10 mg/kg IV weekly,Paclitaxel*,Arm B,AMG 386 3 mg/kg IV weekly,Paclitaxel,Arm C,Placebo IV weekly,Paclitaxel,Open-label AMG 386 10 mg/kg IV weekly,Tr
14、eatment until: Progressive Disease (PD) Unacceptable toxicity Consent withdrawn,R A N D O M I Z A T I O N,*Paclitaxel 80 mg/m2 IV weekly, 3 weeks on/1 week off,Tumor assessments: CT or MRI scans of the chest, abdomen, and pelvis every 8 weeks CA-125 lab values, centrally every 8 weeks and locally as
15、 needed,This study was conducted at 38 sites in 5 countries 161 patients were randomized,入选标准：,Histologically or cytologically documented epithelial ovarian (FIGO stage II-IV), fallopian tube, or primary peritoneal cancerRadiographically documented progression per RECIST or CA-125 (GCIG Criteria) Me
16、asurable or non-measurable disease 3 previous anticancer therapies, but at least one platinum-containing regimenAdequate renal and hepatic functionGOG performance status of 0 or 1,PFS结果：,*PFS is defined as time from randomization to disease progression per RECIST, CA-125 (GCIG criteria), clinical progression, or death.,分层PFS风险分析：,*HRs with 80% confidence intervals.,
