2023V4版NCCN前列腺癌指南解讀之基因檢測(cè)如何指導(dǎo)精準(zhǔn)治療

強(qiáng)烈建議患有轉(zhuǎn)移性去勢(shì)敏感性前列腺癌的患者接受雄激素剝奪療法 種情況下使用ADT單一療法。強(qiáng)化治療方案包括ADT與阿比特龍 (abiraterone)、阿帕魯胺(阿帕他胺，apalutamide)或恩雜魯胺(恩特龍的細(xì)顆粒制劑可作為2B類(其他推薦選項(xiàng))添加到ADT中。IatieafCantensEQ\*jc3\*hps14\o\al(\s\up0(D),r)EQ\*jc3\*hps14\o\al(\s\up0(wit),orro)EQ\*jc3\*hps14\o\al(\s\up0(oc),mg)EQ\*jc3\*hps14\o\al(\s\up2(h),e)EQ\*jc3\*hps14\o\al(\s\up2(TD),an)EQ\*jc3\*hps14\o\al(\s\up3(P),1)ofor▲NCCN指南：轉(zhuǎn)移性去勢(shì)敏感性前列腺癌的全身治療勢(shì)復(fù)發(fā)性)。CRPC是指盡管血清睪酮處于去勢(shì)水平(<50ng/dL),但水平(<50ng/dL;<1.7象(MO)的CRPC患者，如果PSA倍增時(shí)間(PSADT)大于1可以考慮繼續(xù)ADT進(jìn)行監(jiān)測(cè)(首選),因?yàn)檫@些患者的疾病病史相對(duì)惰較短(≤10個(gè)月)EQ\*jc3\*hps14\o\al(\s\up3(trea),and)EQ\*jc3\*hps14\o\al(\s\up3(m),co)EQ\*jc3\*hps14\o\al(\s\up3(e),n)EQ\*jc3\*hps14\o\al(\s\up3(n),t)EQ\*jc3\*hps14\o\al(\s\up3(t),nue)EQ\*jc3\*hps14\o\al(\s\up2(M),a)EQ\*jc3\*hps14\o\al(\s\up2(tain),con)EQ\*jc3\*hps14\o\al(\s\up2(rrent),erpe)EQ\*jc3\*hps14\o\al(\s\up2(t),c)EQ\*jc3\*hps14\o\al(\s\up2(n),s)EQ\*jc3\*hps14\o\al(\s\up2(t),e)EQ\*jc3\*hps14\o\al(\s\up2(Pr),A)EQ\*jc3\*hps14\o\al(\s\up2(o),p)EQ\*jc3\*hps14\o\al(\s\up2(for),alu)EQ\*jc3\*hps14\o\al(\s\up2(r),t)EQ\*jc3\*hps14\o\al(\s\up2(e),a)EQ\*jc3\*hps14\o\al(\s\up2(r),i)EQ\*jc3\*hps14\o\al(\s\up2(og),do)EQ\*jc3\*hps13\o\al(\s\up2(Co),per)EQ\*jc3\*hps13\o\al(\s\up2(s),o)EQ\*jc3\*hps13\o\al(\s\up2(e),e)EQ\*jc3\*hps14\o\al(\s\up2(evi),tas)EQ\*jc3\*hps14\o\al(\s\up2(de),tas)EQ\*jc3\*hps14\o\al(\s\up2(n),o)EQ\*jc3\*hps14\o\al(\s\up2(c),s)EQ\*jc3\*hps13\o\al(\s\up2(PSA),mag)EQ\*jc3\*hps13\o\al(\s\up2(a),g)EQ\*jc3\*hps14\o\al(\s\up2(id),et)EQ\*jc3\*hps14\o\al(\s\up2(e),a)EQ\*jc3\*hps14\o\al(\s\up2(nceo),stasos)EQ\*jc3\*hps14\o\al(\s\up3(a),c)EQ\*jc3\*hps14\o\al(\s\up3(rol),ate)EQ\*jc3\*hps14\o\al(\s\up3(u),g)EQ\*jc3\*hps14\o\al(\s\up3(ta),o)EQ\*jc3\*hps14\o\al(\s\up3(m),ry)EQ\*jc3\*hps14\o\al(\s\up3(d),1)EQ\*jc3\*hps14\o\al(\s\up3(t),o)TabieofContensEQ\*jc3\*hps15\o\al(\s\up2(utat),MB)EQ\*jc3\*hps15\o\al(\s\up2(o),t)EQ\*jc3\*hps15\o\al(\s\up2(n),e)EQ\*jc3\*hps15\o\al(\s\up2(a),st)EQ\*jc3\*hps15\o\al(\s\up2(l),i)EQ\*jc3\*hps15\o\al(\s\up2(bu),ng?)2017年5月，F(xiàn)DA批準(zhǔn)帕博利珠單抗(一種抗PD-1抗體)用于治療不發(fā)生進(jìn)展，并且沒有令人滿意的替代治療方案。該批準(zhǔn)是基于5項(xiàng)涉及研究，客觀緩解率為40%(59/149)。所有患者既往接受過1種或多種觀緩解，另1例疾病穩(wěn)定超過9個(gè)月。研究中，10例有非內(nèi)臟轉(zhuǎn)移(骨=7;淋巴結(jié)=2;骨和肝=1)的CRPC期進(jìn)展性前列腺癌患者，其中74%曾因轉(zhuǎn)移性前列腺癌接受過2種或2其中4例經(jīng)證實(shí)部分緩解。8例(34.8%)患者病情穩(wěn)定。中位隨訪7.9個(gè)月后，61%的患者發(fā)生了與治療相關(guān)的不良事件。17%的患者發(fā)生了3-4級(jí)事件(即4級(jí)脂肪酶升高、3級(jí)周圍神經(jīng)病變、3級(jí)虛弱、3級(jí)疲勞)。404892744POneadditionalpatientexperiencedunconfirmeCl,confidenceinterval;CR,completeresponse;ORRrate;PD,progressivedMSI狀態(tài)的患者中評(píng)估了帕博利珠單抗。隊(duì)列1和2分別納入了PD-L1陽性(n=133)和PD-L1陰性(n=66)的前列腺癌患者。隊(duì)列3包括率在隊(duì)列1為5%95%CI,2%-11%)在隊(duì)列2為3%95%CI,1%-11%)。TABLE2.SummaryafRResporseassessedperv1,1bycentralradioResponseassessedperPCWG3-modifiedRECISTv1.1baselinePSAmeasurResponsetate,No.(%:缺陷的患病率估計(jì)為2%~5%,可以通過DNA檢測(cè)或免疫組織化學(xué)進(jìn)行Network*,Enzalutamlde"fcategoryEQ\*jc3\*hps11\o\al(\s\up2(f),a)EQ\*jc3\*hps11\o\al(\s\up2(u),p)EQ\*jc3\*hps11\o\al(\s\up2(t),ar)EQ\*jc3\*hps11\o\al(\s\up2(i),b)EQ\*jc3\*hps11\o\al(\s\up2(n),/a)EQ\*jc3\*hps11\o\al(\s\up2(cer),irat)EQ\*jc3\*hps11\o\al(\s\up2(t),e)Otaparib/abiraterone"#,nnn,999fo,Radium-223'"torsym*OtherrocommondedroPriornovolhormonetherapyCabazitaxelicarboplRucaparibforBRCAmutTalazoparit/enealutamiAhiraterone"+doramethasongnn.wPriordocetaxelneprornovelhoNirapariblabirateroTalazaparib/onzalutamideforHRLutetiumLu177wipivotidetetraMtovantroneforpallationinaymptomatiepabontPembrolgumabtorMSHH,dWNR.▲NCCN指南：關(guān)于帕博利珠單抗在mCRPC全身治療中的推薦療效，這些患者的TMB可評(píng)估。其中102例患者(13%)有TMB-H狀態(tài)。在TMB-H組的102例患者中，帕博利珠單抗治療后30例達(dá)到客觀緩解(29%;95%CI,21%-39%),非TMB-H組的688例患者中有43顧性研究表明，11%-33%的CDK12突變mCRPC患者對(duì)PD-1抑制劑(即藥物(允許但不要求)治療后出現(xiàn)進(jìn)展的mCRPC患者中，評(píng)估了每日2EQ\*jc3\*hps14\o\al(\s\up7(nnliiam),Alton)EQ\*jc3\*hps14\o\al(\s\up7(te),a)patientswereallowodA2CartrmedORRbyBICPatientsrandomizedbr▲Ⅲ期PROfound研究的設(shè)計(jì)P=.02),盡管對(duì)照組131例患者中有86例(66%)在疾病進(jìn)展后轉(zhuǎn)而BRCA1,BRCA2orATMmCRPC(fin)0Tmesinomsdoniatenimee*突變患者的OS的HR為0.93(95%CI,0.53-1.75)。此外，PROfound帕利組2例和對(duì)照組2例),2例患者有RAD51D突變(奧拉帕利組2例和對(duì)照組2例),沒有患者有RAD51C突變。PROfound中PPP2R2A由于PROfound試驗(yàn)的良好療效數(shù)據(jù)，F(xiàn)DA于2020年5月批準(zhǔn)奧拉帕利(每日2次，每次300mg)用于攜帶14個(gè)基因(BRCA1、BRCA2、AstraZenecaPharmaceuticals,LP)foradultpatientswithdeldeleteriousgermlineorsomatichomologousrecombinationrepaimetastaticcastration-resistantprostatecancer(mCRPC),whohaveprogressedfollowingpriortreatmentwithenzalutamideorabirater▲2020年5月FDA批準(zhǔn)奧拉帕利用于HRR突變mCRPCSYSTEMICTHERAPYEORN1CRPC.ADENOCARCINOMA,Nopriordocetaxelnoprlorn,Niraparib/abiratorone".,for*OthersocondaryhoPrlornovolhormonetherapyingpoiordocotaxglnmm,Niranadhlahlusaoanint-BBGAmutaTalazoparibienzalutamideAbiraterone"+dexamethasone'mn,OthersecondaryhoPriordocotaxellnopriornovelhormonPrlordocotaxelandpriornoyLutotiumLu177vipivFombrolCumabTorHSTHCNVR,OrTMa210mu,RucaparibforBACAMitoxantroneforpallatianinsymptomaticNiraparib/abiratorone"forBRCAmutationOlaparib/abiraterono"tnnn,4fo,Radium-223'"torsymptomaticbonTalazoparibienzalutamid▲NCCN指南：關(guān)于奧拉帕利單藥在mCRPC全身治療中的推薦或BRCA2突變、既往接受過一種新型激素藥物+一種紫杉烷化療的中，這一比例為43.5%(95%CI,31.0%-56.7%)。關(guān)鍵次要終點(diǎn)中位影像學(xué)PFS為9.0個(gè)月(95%CI,8.3-13.5個(gè)月)。TRITON2的最終分析ConfirmedORR,Na(%;9▲TRITON2臨床試驗(yàn)中盧卡帕利治療的中位影像學(xué)PFS在隨機(jī)Ⅲ期TRITON3研究中，患有mCRPC且具有胚系或體細(xì)胞P<.001)。在各組中攜帶BRCA突變的201例患者和10Na.atRisk(no.offBRCA1或BRCA2突變患者的可選治療方案。盧卡帕利不應(yīng)用于JablesfContertSYSTENICTHERAPYFORM1CRPC:ADENOCARCINNirapanblablratorongy,forBRCAmutationfcatogory們,Olapanb/ahiratorone",mon,Talazoparntb/enralutamideforHRRm"蘭(category1)*Cebaztaxel/carbool,Niraparlb/abiratorone"H,arforBRCAmutationfcatogoBadium.223tacAxmotomaticAbiratorgne"adoxamethasoPriordocotaxelnopriornoveRadum·223'"forsymptoma,Talazoparib/enzalutPriordocetaxelandpriornovalhomonetherepymm,,MitoxantroneforpalliationinsymptomaticpaPombrolizumabforMSLH▲NCCN指南：關(guān)于盧卡帕利單藥在mCRPC全身治療中的推薦PROpel試驗(yàn)是一項(xiàng)國際性雙盲Ⅲ期試驗(yàn)，在796例mCRPC患者(不的HR為0.50(95%CI,0.34-0.73)。EQ\*jc3\*hps13\o\al(\s\up3(Pr),P)EQ\*jc3\*hps13\o\al(\s\up3(ima),FS)EQ\*jc3\*hps13\o\al(\s\up3(tn),Dr)EQ\*jc3\*hps13\o\al(\s\up3(polnt),wtty)PROpel試驗(yàn)的OS數(shù)據(jù)在2023年ASCO泌尿生殖系統(tǒng)癌癥研討會(huì)上發(fā)EQ\*jc3\*hps13\o\al(\s\up7(NR:),*Ca)EQ\*jc3\*hps13\o\al(\s\up7(Not),lcu)EQ\*jc3\*hps13\o\al(\s\up7(reached),edusin)未接受新型激素療法或多西他賽治療的mCRPC患者(1類),以及既往在去勢(shì)敏感情況下接受過多西他賽治療的mCRPC患者fshe▲2023年5月，F(xiàn)DA批準(zhǔn)奧拉帕利聯(lián)合阿比特龍治療BRCA突變SYSTEMICTHERAPYEORN1CRPC:ADENNopriordocotaxetnoprioAbiraterong"n,oe(eategoNirapatib/abiraterengt,mtorBRCAmutaTOiapanbabiraterone"torBRCAmutatlon(categonyRadom-22JwTorsymptoPriornovelhormonetheNirapanb/abiraterone".RtorBRCAmutationfcategoryRucaparibforBRCAmut,TaiazoparibVonzalutamidefOtherrocommondedroAbimtorong"+dexamothasonerun,NirananVablratamnet,tocBBObpartbabronforBRCAOtherrecommendodregimengCabazitaxellcarboplaMitoxantroneforpalliationinsymptomaicpatient,OlpartbforHRRmoeuuPembrolizumabforMSLH.,Radium-223"""torsymptomaticbonem放標(biāo)簽、國際性Ⅱ期TALAPRO-1試驗(yàn)納入了127例HRRm進(jìn)展性個(gè)月后的客觀緩解率為29.8%(95%CI,21.2-39.6)。拉唑帕利組的中位影像學(xué)PFS未達(dá)到(95%CI,27.5個(gè)月-未達(dá)到),對(duì)照組為21.9個(gè)月(95%CI,16.6-25.1)(HR,0.63;95%CI,0.51-0.78;EQ\*jc3\*hps12\o\al(\s\up2(s),m)m82#2s量最*帶;AcorsietentheatnrentefectwasseenforHNvestig=tor-assessedIPFS.HR064195%C1,050-0B1.P<m更有利于HRR缺陷亞組(0.46[95%CI,0.30-0.70;P=.0003]vs降低77%(HR0.23;95%CI,0.10-0.53;P=.0002),而非BRCAHRR變異患者的相應(yīng)降幅為34%(HR,0.66;95%CI,0.治療的50名參與者中,相應(yīng)的HR為0.57,不顯著(95%CI,0.28-1.16;爭議(2B類),因?yàn)樵谶@一情況下，該聯(lián)合治療與PARP抑制劑單獨(dú)治fsnae▲2023年6月，F(xiàn)DA批準(zhǔn)他拉唑帕利聯(lián)合恩雜魯胺治療HRR突變NetworkGYSTENICTHERAPYEORNICREQ\*jc3\*hps10\o\al(\s\up0(u),)EQ\*jc3\*hps10\o\al(\s\up0(cef),)EQ\*jc3\*hps10\o\al(\s\up0(n),)EQ\*jc3\*hps10\o\al(\s\up0(c),)Olaparib/abiraterone"Talaropanb/orualutimidoforHRRm"(Priornovulhormonetherapyinepri*CabazitaxellcarboNiraparitvabiratarone",HiR*torBRCAmutationfeategory2OlaparibforHRRm"(cateRuzaparttoraRcxmutatiancbonemetaTalazoparib/orgalutamideforHRRAbiraterpnenTPrhor.decataxel'neprornovethormoneEnzalutamide"(eatog,MitoxantronetorpattatieninaymptomatiepOlaparib/absaterong"Af,Radum-223'"fotsymptoPriordocataxstandpriorno*Cabazitaxol/carboplatin山PambroltrumabforNSIH,dMNR.OrTMB210m,Radium-22y""forSymucaparibforBRCAmutab的推薦患者和另外247例無HRRm的患者中比較了尼拉帕利+阿比特龍與安慰化療和新型激素治療，分別有3.1%和20.1%的HRRmbbedfurmcopcthemutherupytutmEQ\*jc3\*hps12\o\al(\s\up5(AH*),ne)EQ\*jc3\*hps12