晚期非小细胞肺癌一线化疗后的治疗策略

晚期非小细胞肺癌一线化疗后的治疗策略1整理ppt什么叫晚期肺癌？一线化疗后可能有几种情况？一线化疗后的治疗有哪些选择？ASCO：thetreatmentofstage

4NCSLC2整理ppt什么叫晚期肺癌？不可手术的Ⅲ期Ⅳ期3整理ppt一线化疗后可能有几种情况？进展稳定、稍有缩小或难以精确测量局部或完全缓解发现了新病灶，但不能肯定为进展目标病灶与非目标病灶的反响不同化疗有效但因为医疗或非医疗的原因改变治疗4整理ppt一线化疗后的治疗：不同的情况维持治疗是指在完成标准的几个周期化疗且疾病得到控制后再接受的化疗。理论根底：GoldieandColdman假设，早期使用非交叉耐药的药物可以在耐药性产生前增加杀伤肿瘤细胞的效能。使治疗效果最优化，杀死更多的肿瘤细胞。完全缓解、局部缓解或者疾病稳定的患者最有可能从维持治疗中获益。但同时也延长了治疗时间，且化疗的毒性反响可在体内蓄积，导致过度治疗。一线化疗失败后的治疗严格意义上属于挽救治疗，但两者并没有本质区别。5整理ppt一线化疗后的治疗有哪些选择？放疗中医药治疗及最正确支持治疗化疗分子靶向治疗联合治疗6整理ppt放疗

有以下情况者一般不做根治性放疗：两肺或全身广泛转移胸膜广泛转移有癌性胸腔积液癌性空洞或肿瘤巨大严重肺气肿心包或心肌有癌瘤侵犯者伴有感染，抗炎治疗不能控制肝、肾功能严重受损，KPS<60分者。姑息放疗可能有价值〔心理支持、老年人〕7整理ppt药物维持治疗二线细胞毒药物，并非都是单抗类靶向治疗药物表皮生长因子受体酪氨酸蛋白激酶抑制剂联合治疗

8整理pptPemetrexedJuly6,2021—FDAhasapprovedpemetrexedforthemaintenancetherapyofadvancedormetastaticNSCLC.Pemetrexedisthefirstdrugindicatedasamaintenancetherapyinthissetting.9整理pptJMEN研究，patientsreceivedeitherpemetrexed(n

=441)orplacebo(n

=222),alongwiththebestsupportivecare.Patientshadadvancedormetastatic(stage

3Bor4)NSCLC(bothsquamousandnonsquamoussubtypes)thathadnotprogressedafter4cyclesofinitialplatinum-basedchemotherapy.10整理pptForallpatientsinthestudy,thepemetrexedtreatmentgrouphadanoverallsurvivalof13.4months,comparedwith10.6monthsfortheplacebogroup.Forthenonsquamoussubgroup,overallsurvivalwas15.5monthsforpatientstakingpemetrexedand10.3monthsforpatientstakingplacebo(P

=.002).11整理pptthetrialwasnotdesignedtoindicatewhethermaintenancetherapywassuperiortousingpemetrexedattimeofdiseaseprogression.don'tthinkwehavetheanswerastowhenitisbesttostartpemetrexed.Shouldwestartimmediatelyafterstandardchemotherapyorlateron?12整理ppt多西紫杉醇第一个被认可的二线治疗药物。Fidias等，进展期NSCLC，4周期卡铂联合吉西他滨的诱导化疗后，对治疗有反响或者稳定的患者随机分成2组，一组立即接受多西他赛，另外一组于疾病进展时接受多西他赛作为挽救治疗(延迟组)。结果：立即组的总有效率高于延迟组(42．5VS9．9)；中位生存时间，立即组为11．9个月，延迟组9．1个月，但无统计学意义；中位PFS，立即组为6．5个月显著高于延迟组2．8个月(P<0．0001)，生活质量评估两组无显著性差异。13整理ppt分子靶向药物：厄洛替尼SATURN，889例一线化疗后疾病未进展的晚期NSCLC患者，随机分组后给予150mg/d维持治疗或抚慰剂，直至疾病进展。维持治疗显著改善了患者的PFS，疾病进展风险显著降低了29%，其中EGFR免疫组化〔IHC〕阳性患者疾病进展风险降低31%。无论年龄、种族、病理类型和吸烟史如何，均可从维持治疗中显著获益。EGFR突变者疾病进展风险大幅度降低90%，野生型患者降低22%。14整理ppt分子靶向药物：厄洛替尼SATURN，维持治疗显著延迟了疼痛病症的出现，对其他各生活质量指标也无不利影响。在维持治疗组中发生率超过10%的不良反响仅有皮疹和腹泻，但到达3～4级的比例很低。患者经一线化疗后仍有病症〔如咯血、胸痛和胸闷等〕，维持治疗的价值最大。15整理ppt分子靶向药物：吉非替尼日本，WJTOG0203研究，一线化疗后疾病未进展的晚期NSCLC患者给予吉非替尼维持治疗或抚慰剂，结果维持治疗组PFS有显著延长，但OS未见显著获益。但在亚组分析中，有腺癌和吸烟患者可从吉非替尼维持治疗中显著获得生存益处。16整理ppt分子靶向药物与化疗效果比较韩国李〔Lee〕：313例从不吸烟、PS0－2分、具有足够器官功能的初治ⅢB/Ⅳ期肺腺癌患者，随机给予吉非替尼〔250mg，口服，每日1次〕或GP方案化疗〔吉西他滨1250mg/m2，d1、d8；顺铂80mg/m2，d1，每3周为1个周期，共3个周期〕。主要终点为OS；次要终点为ORR、PFS期和毒性。初次疾病进展后，依照临床医师的推荐接受二线治疗。309例，其中女性占88.7%，Ⅳ期患者占90.0%，PS2分者占9.1%。结果：吉非替尼组ORR优于GP组〔53.5%对42.0%〕，但无显著差异，而中位PFS〔5.9个月〕显著优于GP组〔5.8个月，HR=0.737，P=0.0063〕。17整理ppt分子靶向药物与化疗合用有待研究：EGFR突变患者应用时机化疗与TKI的使用顺序单药维持治疗EGFR-TKI耐药的后续治疗对野生型患者的作用贝伐单抗、西妥昔单抗18整理pptJMEN研究中抚慰剂组在进展后仅有19％的患者使用了培美曲塞作为二线治疗。SATURN中抚慰剂组只有16％的患者在进展后使用了厄洛替尼。19整理pptASCO：

thetreatmentofstage

4NCSLCNovember24,2021—GuidelinesforusingchemotherapyinhavebeenupdatedbytheASCO.JClinOncol.PublishedonlineNovember16,2021.20整理pptcytotoxicsinfirst-linetreatmentTherecommendationsforusingcytotoxicsinfirst-linetreatmenthavenotchanged,butthereareseveraladditionalrecommendationsabouttheuseoftargetedagents.21整理pptcytotoxicsinfirst-linetreatmentForpatientswithaperformancestatusof0or1,aplatinum-based2-drugcombinationofcytotoxicdrugsisrecommended.Forpatientswithaperformancestatusof2,single-agentchemotherapyisrecommended.Nonplatinumcytotoxicdoubletsareacceptableforpatientswithcontraindicationstoplatinumtherapy.First-linechemotherapyshouldbestoppedatdiseaseprogression,orafter4cyclesinpatientsnotrespondingtotreatment.Two-drugcytotoxiccombinationsshouldbeadministeredfornomorethan6cycles.22整理pptcytotoxicsinfirst-linetreatmentPlatinumcompoundsarepreferredovernonplatinumcompoundsbecausetheyaresuperiorinresponserateandmarginallysuperiorinoverallsurvival,theauthorsexplain.Thechoiceofeithercisplatin(Platinol)orcarboplatin(Paraplatin)isacceptablebecauseneitherisconsistentlysuperior,theynote;cisplatinmighthavebetterefficacybutcarboplatinmighthavelesstoxicity.23整理ppttargetedagentsinfirst-linetreatmentNewintheupdatearerecommendationsontheuseoftargetedagentsinfirst-linetreatment,asfollows:24整理ppttargetedagentsinfirst-linetreatmentTheadditionofbevacizumab(Avastin)tocarboplatin/paclitaxelisrecommended,exceptinpatientswithcertaincharacteristics(i.e.,thosewithsquamouscellcarcinomahistology,brainmetastases,clinicallysignificanthemoptysis,inadequateorganfunction,aperformancestatusgreaterthan

1,therapeuticanticoagulation,clinicallysignificantcardiovasculardisease,ormedicallyuncontrolledhypertension).25整理ppttargetedagentsinfirst-linetreatmentTheadditionofcetuximab(Erbitux)tocisplatin/vinorelbinecanbeconsideredinpatientswithtumorstestingpositiveforepidermalgrowth-factorreceptor(EGFR),asmeasuredbyimmunohistochemistry.26整理ppttargetedagentsinfirst-linetreatmentFirst-linegefitinib(Iressa)usecanberecommendedforpatientswithactivatingEGFRmutations.However,ifEGFRmutationstatusisnegativeorunknown,cytotoxicchemotherapyispreferred.Erlotinib(Tarceva)orgefitinibshouldnotbeusedinfirst-linetherapyincombinationwithcytotoxicsinunselectedstage

4NSCLCpatients.27整理pptSecond-andThird-LineTreatment

Therehasbeenachangeinthedrugsrecommendedforuseinsecond-linetherapy.Previously,onlydocetaxel(Taxotere)wasrecommendedforuseafterprogressiononplatinum-basedfirst-linetherapy,andgefitinibwasrecommendedafterafailureofbothplatinum-basedtherapiesanddocetaxel.Nowtheguidelinesstatethatdocetaxel,gefitinib,erlotinib,andpemetrexedareacceptableassecond-linetherapies.28整理pptSecond-andThird-LineTreatmentTheguidelinecommitteenotesthatpemetrexedwasrecentlyapprovedbytheUSFoodandDrugAdministrationformaintenancetherapyinNSCLC,butthisisbasedonrecentlypresenteddatathatwere"outsidethescope"ofthecomprehensivedatareviewundertaken.29整理pptSecond-andThird-LineTreatmentThird-linetherapywitherlotinibcanberecommendedforpatientswithaperformancestatusof0to3whohaveprogressedonoraftersecond-linetherapyandwhohavenotpreviouslyreceivederlotiniborgefitinib.Thereisnotenoughevidencetomakearecommendationfororagainstusingacytotoxicdrugasathird-linetherapy30整理pptSecond-andThird-LineTreatmentThereisinsufficientevidencetorecommendtheroutineuseofmolecularmarkerstoselectsystemictreatmentinpatientswithmetastaticNSCLC.31整理pptDrugEstimatedCostfor2CyclesofTherapy

($)

Bevacizumab14,040Carboplatin146Cetuximab18,981Cisplatin68Docetaxel5,060Erlotinib9,114Gefitinib4,255Gemcitabine6,914Irinotecan527Paclitaxel201Pemetrexed9,682Vinorelbine257

32整理pptDrugEstimatedCostforTherapyMostofthecanceragents(>90%)approvedbytheFDA)inthepast4yearscostmorethan$20,000fora12-weekcourseoftherapy,1.2-monthsurvivalbenefitwithcetuximabplusaplatinum-basedchemotherapycomparedwithchemotherapyalonewashailedasthe"newstandard"forNSCLC.cetuximabforNSCLC,whichcosts$80,000foran18-weekcourse.33整理pptDrugEstimatedCostforTherapybevacizumabformetastaticbreastcancerprovidesprogr