CGOG1001轉(zhuǎn)化性病例3例課件

1、HER2陽性胃癌轉(zhuǎn)化性治療的討論 成功的因素？張小田 北京大學(xué)腫瘤醫(yī)院 消化內(nèi)科1Bang et al; Abstract 4556, ASCO 2009ToGA研究開啟胃癌靶向藥物治療的新時代 后ToGA 研究時代。Go into real world，we know.Trastuzumab：Her-2陽性胃癌的治療選擇！病理科規(guī)范并標(biāo)準(zhǔn)化的檢測！必要時，原發(fā)灶和轉(zhuǎn)移灶的檢測！Go into real world， we dont know yet.維持治療？新輔助治療？后Trastuzumab治療？優(yōu)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免疫組化Her-2（+） 中低分化腺癌，Lauren分型為混合型復(fù)旦大學(xué)腫瘤醫(yī)院基線腹盆增強(qiáng)CT(2012.4)c T: 4 M: M1（ascites？） N: positive 治療經(jīng)過化療2012-04 至 2012-9曲妥珠單抗 + 奧沙利鉑卡培他濱化療6周期不良反應(yīng)粒細(xì)胞減少II，白細(xì)胞減少II 血小板降低II 末梢神經(jīng)毒性I 胃鏡復(fù)查治療前治療六周期后胃鏡對比顯示：原發(fā)灶好轉(zhuǎn)影像學(xué)評估：PR(縮小53.3%）2周期化療后評效PR 4周期化療評效維持PR 6周期

13、化療評效維持PR 治療前影像學(xué)表現(xiàn) 2012-9-26 手術(shù)治療2012-9-26 腹腔鏡探查：無腹水，未見轉(zhuǎn)移種植。腫物位于胃體小彎累及胃竇，約4*5cm，D2淋巴結(jié)清掃術(shù)ypT4aN3M1低分化腺癌伴粘液腺癌，侵達(dá)漿膜，脈管癌栓及神經(jīng)束侵犯，淋巴結(jié)可見癌轉(zhuǎn)移17/36，原發(fā)灶（TRG：2-3級）淋巴結(jié)完全緩解術(shù)后原發(fā)灶Her-2檢測HER2(+)HER2/CEP17比值：1.3術(shù)后：HerceptinX單藥44月后，盆腔積液，卵巢轉(zhuǎn)移PFS：10.2 月AbraxaneS1二線治療中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，腸型，HER2（3）基線腹盆增強(qiáng)CT(2011.9)c T: 4 M: M0 N: positive 2011.92011.11化療XELOXH4不良反應(yīng)： 耐受可PR再次建議手術(shù)，患者拒絕治療經(jīng)過化療2011-9 至 2011-11曲妥珠單抗 + 奧沙利鉑卡培他濱化療4周期不良反應(yīng)： 耐受可PR：胃周淋巴結(jié)僅有4組7組可見，可手術(shù)，患者拒絕隨訪至今，胃周淋巴結(jié)穩(wěn)定，建議手術(shù)，仍拒絕2011.92011.112013.32013.3 PDPFS：18m重新引入XELOXH？患者猶豫中3例患者病例特點(diǎn)總結(jié)共同點(diǎn)：HER2過表達(dá)，經(jīng)XELOXH化療后PR，可手術(shù)不同點(diǎn)：Case 1Case 2Case 3老年男性中年女性青年男性部位胃體胃體EGJ病理中低分化低分化印戒中分化混合型彌漫型腸型HER2檢測323CISH（）治療前臨床分期cT3NM1cT3NM1cT3NM1手術(shù)病理分期ypT1bN3M1ypT4aN3M1NAPFS6.1月10,2月18月特殊腦轉(zhuǎn)移腹腔內(nèi)播散，治療后轉(zhuǎn)陰始終為局部病變醫(yī)生觀點(diǎn)爭議不建議手術(shù)建議手術(shù)HER2陽性胃癌轉(zhuǎn)化性治療的總結(jié) Her-2檢測：應(yīng)作為常規(guī) 原發(fā)灶 vs 轉(zhuǎn)移灶 ； 治療前 v