2020 NCCN 前列腺癌指南V2版更新

1、2020NCCN前列腺癌指南V2版更新NationalComprehensiveCancerNetworkNCCNCI4nkcalPracticeGuidelinesinOncology(NCCNGuidehnesc)ProstateCancerVersjon2.2020May21.2Q20NCCNorghCCNQu1grP4inliEContinuBHKCh5月15日，FDA加速批准卢卡帕利(Rucaparib)用于治疗预先接受过雄激素受体靶向疗法和紫杉烷类化疗的BRCA突变(胚系和/或5月19日，FDA批准了奥拉帕利(Olaparib)用于治疗既往接受过恩杂鲁胺(enzalutamide)

2、或阿比特龙(abiraterone)治疗的同源重组修复(HRR)基因突变的转移性去势抵抗性前列腺癌(mCRPC)。随着两款PARP抑制剂连续获批，NCCN于2020年5月21日发布了前列腺癌指南2020V2版。指南更新要点将奥拉帕利二线治疗HRRmmCRPC患者的推荐等级从2B级提升至1级。并且在脚注部分将HRR基因突变人群明确为BRCA1、BRCA2、ATM、BARD1、BRIP1、CDK12、CHEK1、CHEK2、FANCL、PALB2、RAD51B、RAD51C、RAD51D、RAD54L基因胚系和/或体系突变患者。另外，由于临床试验中奥拉帕利用于PPP2R2A突变患者存在不利风险，奥

3、拉帕利不推荐在PPP2R2A突变患者中。指南增加卢卡帕利作为BRCAmmCRPC患者二线治疗方案推荐等级为2A级。如果患者不适合化疗，即使未使用紫杉烷类药物也可以考虑使用卢卡帕利。NCCN闻;匚NjZui曰里怦gl睥罐耳qijC；ofil&riLEdscuaspn芻黑1鳥皿爾NCCNGuidelinesVersion2,2020常鵲k，PrastateCancerSYSTEMICTHERAPYFORM1CRPC:ADENOCARCINOMA*4*11FIRST-LINETREATMENTSECCNO-ILIHETREA1TMENTPrerenredregmens:卜AblraMfone1fea

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14、rkti“fit册churcHwpy.wdpanbC4oImcwnered爭wonir閉.曲昭tiWMiJBwri”hwndgl們指南更新基于的临床试验针对奥拉帕利的指南更新主要基于III期PROfound临床试验。该硏究评估了奥拉帕利用于既往接受过新型内分泌治疗(例如恩杂鲁胺或阿比特龙)后进展的mCRPC患者的疗效和安全性。所有患者都有HRR基因突变，其中队列A患者携带BRCA1、BRCA2、ATM突变，队列B患者携带任何其他12种基因突变。患者被随机分配接受奥拉帕利或新型内分泌治疗。队列A患者中，奥拉帕利组中位无进展生存期(PFS)为7.4个月，显著长于对照组的3.6个月(HR=0.34,

15、95%CI,0.25-0.47,P.nlTrcSurvivalin*hprlAlJCOdr.pvstHH匚芝-碁&=一l/amlhsRjncornuEinMrdianimaOiajunb7.4COflliTOl1IHazarlritic詁rprojmiMnCrdtJlhr0349%ClE025-047PD.(IO1hlatRiikOlhpiiiblfi214：12ii116Q2DOI*277兀53423TZ6MISII111ControlS37147442220119273J322I112GU0104QMwlhs用Nq.aiHisbOipirib绑2i91BITS1451411.0ti10DC

16、ontil.1J12)730II152Q19f1553332211命Dpo-MryhEJlh占点=qrqEcj队列A（上），队列A+B（下）然而，亚组分析中显示，奥拉帕利治疗PPP2R2A患者PFS显著更差。基于此原因，指南不推荐奥拉帕利用于PPP2R2A突变患者。BCohortsAandBSubgroupHazardRatioforProgressioncrDeath(95%Cl)Genealteralion11fiRCAf1I041(OB-1.39)0RCA2#1102】(0B-0.32)ATM11.M(061-117)CDK12点0.74044-1.31)CHEK2087(0.21-4.

17、U|PPP2R2A116.61(141-46.41RAD54L033(0.05-2.54)I1I1I1I1ICOGC.2510040Q1600OlaparibBetterControlBetter指南针对卢卡帕利的更新主要基于II期TRITON2临床研究。该硏究纳入包括BRCA1/2在内的15个DNA损伤修复(DDR)基因突变患者，平估了卢卡帕利用于既往接受雄激素受体靶向治疗和化疗后进展的mCRPC患者的疗效和安全性。ScreeningIdentificationofadeleterioussomaticorgermlinealterationinDDRgene*DDRgenesATMCHEK

18、2BRCA1BARD1FANCABRCA2BRIP1N&NCDK12PALB2RAD51RAD51BRAD51CRAD51DRAD54L结果显示，在可评估的62例患者中，BRCA1/2突变患者的客观缓解率(ORR)达到44%，并且硏究者评价的胚系和体系BRCA1/2突变患者的ORR相似38.1%(8/21;95%CI,18.1%-61.6%)vs.48.6%(17/35;95%CI,31.4%-66.0%)。基于该硏究，FDA加速批准卢卡帕利用于晚期经治mCRPC患者，NCCN指南作2A级推荐。卢卡帕利对比阿比特龙、恩杂鲁胺或多西他赛的III期临床试验TRITON3(NCT02975934)正在进行中。Robnta(N=62jCaifoncdObjcdiwItesponscR|k,95%Cf44%(3!,5?)DORmnmths(9$%Cl)hNE(M.NE)NL=not呼ahiablc1DefinedpermodiiodRECISTvLlcriteriainiwithnooodkiudhncprogresaonpaFCWQThcrati黑torihcDORwas1.7-24-months.Fiflcenofthe11(5h|piicwithacontimiodobjcciivcresponsehadjDORo