CGOG1001转化性病例3例课件

1、HER2阳性胃癌转化性治疗的讨论 成功的因素？张小田 北京大学肿瘤医院 消化内科1Bang et al; Abstract 4556, ASCO 2009ToGA研究开启胃癌靶向药物治疗的新时代 后ToGA 研究时代。Go into real world，we know.Trastuzumab：Her-2阳性胃癌的治疗选择！病理科规范并标准化的检测！必要时，原发灶和转移灶的检测！Go into real world， we dont know yet.维持治疗？新辅助治疗？后Trastuzumab治疗？优化方案？XStudy design: open label, single arm pha

2、se II studyPrimary endpoint: ORRSecondary endpoints: PFS, HER2 positive rate in Chinese GC pts, OS, safety Pts with HER2+ AGCNo prior CT for advanced diseaseHerceptin8mg/kg first dose, then 6mg/kg Q3WXeloda1000 mg/m2 BID D1-14 Q3WOxaliplatin130 mg/m2, D1 Q3WHerceptin6mg/kg Q3WXeloda1000 mg/m2 BID D1

3、-14 Q3WUntil PD6 cyclesStage IPhase II trial : CGOG1001 (ML25578)XELOX + Herceptin in 1st line therapy of HER2 positive gastric cancerStage IIIf 7 out of the 16 patients show PR/CRTotal N=51Current status 2011.5.21 trial initiated, 13 centers in china2011.6.21 first patient enrolled 2012.8.30 last p

4、atient enrolled N=51 from 364 screened (HER-2 overexpression 14%)stage I: 7 out of the 16 patients show PR/CRCurrently: response evaluation in 50 pts： ORR：79.8 ，CR, 39PR, 9 SD, 1 PD, survival data under follow upCase 1A 57-year old male, Admission to hospital on Nov.2,2011 Endoscopic finding: a larg

5、e ulcer at the gastric angle T3EUS stage: uT3N1M0Nov.2.2011 pathologic findingModerately-poorly differentiated adenocarcinomaLauren classification: Mixed typeHER-2 overexpression : 3+(IHC)FISH(+)Abdominal and pelvic CT (Nov.5,2011)Multidisciplinary EvaluationKPS score: 90PE: no abnormal sign No hist

6、ory of concomitant disease, weight loss of 5kg Tumor marker：CEA:7.69 ng/ml, CA724 ：67.18 IU/mlNormal Organ function. Normal chest CT (Nov.15.2011)Abdomen and pelvic CT：thicken of gastric wall at the gastric angle, Borrmann III Enlargement of lymph nodes of No. 3. 8 and No. 16 (no PET scan, no Laparo

7、scopy)c T: 3 M: M1 N: positive Medically fit, metastatic of para-aorta LN resectable? Unresectable? potentially resectable? 2011.11.16 2012. 2.15: 4 cycles finished, Response : PRCEA and CA724 dropped to normal KPS: 90, symptom alleviated, BW increased with 3 kgAE: easily controlled HFS grade 3(dose

8、 decreased), neutrocytopenia grade 2, thromobocytopenia grade 2,peripheral neuropathy grade 2Response to XELOX+TrastuzumabbaselineFeb.15.2012(4 cycles)Evaluation by endoscope: primary disease progression？ T3T4abaselineFeb.15.2012( 4 cycles)Evaluation by EUS : primary disease progression？Baseline Dec

9、.26.2011 (2 cycles)Feb.15.2012(4cycles)No ascites and peritoneal dissemination poorly differentiated adenocarcimoma，infiltrated to sub-mucosa，next to muscularis proprianegative marginLNM : total： 22/39(No.1:7/10, No.2:0/1, No4sb:2/8, No.4d:2/4, No.5:0/0, No.6:4/9, No.7:2/3, No.9:1/1, No.12:2/3 )pT1b

10、N3M1Distal gastrectomy, (Apr.10.2012)D2+PAND planed, finally only D2 dissection Tumor regression in one meta lymph nodeGrade 1: tumor necrosis and stroma fibrosis HE 100HE 20020-May-2012 trastuzumab+ capecitabinefollow up ：Jun-2012 , headache, 2 lesions in brain30Gys of radiotherapy givenCT scan: me

11、ta at lung, bone, other meta? Poor condition, no further treatment 10-July: sudden death when he got up in the morningOS: 8 months onlyPost surgery evaluation and treatment Case 2A 44-year old female, Admission to hospital on Apr. 2012 Endoscopic finding: a large ulcer at the gastric bodyFamily hist

12、ory： grandma，uncle EUS stage: NDPathological finding，HER2 test免疫组化Her-2（+） 中低分化腺癌，Lauren分型为混合型复旦大学肿瘤医院基线腹盆增强CT(2012.4)c T: 4 M: M1（ascites？） N: positive 治疗经过化疗2012-04 至 2012-9曲妥珠单抗 + 奥沙利铂卡培他滨化疗6周期不良反应粒细胞减少II，白细胞减少II 血小板降低II 末梢神经毒性I 胃镜复查治疗前治疗六周期后胃镜对比显示：原发灶好转影像学评估：PR(缩小53.3%）2周期化疗后评效PR 4周期化疗评效维持PR 6周期

13、化疗评效维持PR 治疗前影像学表现 2012-9-26 手术治疗2012-9-26 腹腔镜探查：无腹水，未见转移种植。肿物位于胃体小弯累及胃窦，约4*5cm，D2淋巴结清扫术ypT4aN3M1低分化腺癌伴粘液腺癌，侵达浆膜，脉管癌栓及神经束侵犯，淋巴结可见癌转移17/36，原发灶（TRG：2-3级）淋巴结完全缓解术后原发灶Her-2检测HER2(+)HER2/CEP17比值：1.3术后：HerceptinX单药44月后，盆腔积液，卵巢转移PFS：10.2 月AbraxaneS1二线治疗中Case 3A 37-year old male, Admission to hospital on Sep

14、. 2011Endoscopic finding: a large ulcer at the EGJbody中分化腺癌，肠型，HER2（3）基线腹盆增强CT(2011.9)c T: 4 M: M0 N: positive 2011.92011.11化疗XELOXH4不良反应： 耐受可PR再次建议手术，患者拒绝治疗经过化疗2011-9 至 2011-11曲妥珠单抗 + 奥沙利铂卡培他滨化疗4周期不良反应： 耐受可PR：胃周淋巴结仅有4组7组可见，可手术，患者拒绝随访至今，胃周淋巴结稳定，建议手术，仍拒绝2011.92011.112013.32013.3 PDPFS：18m重新引入XELOXH？患者犹豫中3例患者病例特点总结共同点：HER2过表达，经XELOXH化疗后PR，可手术不同点：Case 1Case 2Case 3老年男性中年女性青年男性部位胃体胃体EGJ病理中低分化低分化印戒中分化混合型弥漫型肠型HER2检测323CISH（）治疗前临床分期cT3NM1cT3NM1cT3NM1手术病理分期ypT1bN3M1ypT4aN3M1NAPFS6.1月10,2月18月特殊脑转移腹腔内播散，治疗后转阴始终为局部病变医生观点争议不建议手术建议手术HER2阳性胃癌转化性治疗的总结 Her-2检测：应作为常规 原发灶 vs 转移灶 ； 治疗前 v