Efficacy and safety of the ALK inhibitor alectinib in ALK+ non ...

The NP28673 study (NCT01801111) investigated the efficacy and safety of alectinib, a highly selective, CNS-active ALK inhibitor, ... Skiptomaincontent > JournalofClinicalOncology > ListofIssues > Volume33,Issue15_suppl > MeetingAbstract|2015ASCOAnnualMeetingI ArticleTools LungCancer—Non-SmallCellMetastatic ArticleTools OPTIONS&TOOLS ExportCitation TrackCitation AddToFavorites Rights&Permissions COMPANIONARTICLES Nocompanionarticles ARTICLECITATION DOI:10.1200/jco.2015.33.15_suppl.8008JournalofClinicalOncology- publishedonlinebeforeprint May20,2015 EfficacyandsafetyoftheALKinhibitoralectinibinALK+non-small-celllungcancer(NSCLC)patientswhohavefailedpriorcrizotinib:Anopen-label,single-arm,globalphase2study(NP28673). Sai-HongIgnatiusOuxSearchforarticlesbythisauthor,JinSeokAhnxSearchforarticlesbythisauthor,LuigiDePetrisxSearchforarticlesbythisauthor,RamaswamyGovindanxSearchforarticlesbythisauthor,JamesChih-HsinYangxSearchforarticlesbythisauthor,BrettGordonMaxwellHughesxSearchforarticlesbythisauthor,HervéLenaxSearchforarticlesbythisauthor,DenisMoro-SibilotxSearchforarticlesbythisauthor,AlessandraBearzxSearchforarticlesbythisauthor,SantiagoViteriRamirezxSearchforarticlesbythisauthor,TarekMekhailxSearchforarticlesbythisauthor,AlexanderI.SpiraxSearchforarticlesbythisauthor,AliHassanZeaiterxSearchforarticlesbythisauthor,WalterBordognaxSearchforarticlesbythisauthor,BogdanaBalasxSearchforarticlesbythisauthor,SophieGoldingxSearchforarticlesbythisauthor,PeterN.MorcosxSearchforarticlesbythisauthor,Dong-WanKimxSearchforarticlesbythisauthorShowMore ChaoFamilyCompCancerCtrUCIrvineMedclCtr,Orange,CA;SamsungMedicalCenter,Seoul,SouthKorea;KarolinskaUniversityHospitalSolna,Stockholm,Sweden;WashingtonUniversitySchoolofMedicine,St.Louis,MO;NationalTaiwanUniversity,Taipei,Taiwan;ThePrinceCharlesHospital,Brisbane,Australia;CentreHospitalierUniversitaire,HopitalPontchaillou,Rennes,France;ThoracicOncologyUnitTeachingHospitalAMichallon,INSERMU823,Grenoble,France;IRCCSCentroRifOncologico,Pordenone,Italy;QuirónDexeusUniversityHospital,Barcelona,Spain;FloridaHospitalCancerInstitute,Orlando,FL;VirginiaCancerSpecialistsResearchInstitute,USOncologyResearch,Fairfax,VA;F-Hoffmann-LaRocheLtd,Basel,Switzerland;F.Hoffmann-LaRoche,Basel,Switzerland;F.Hoffmann-LaRocheLtd,Basel,Switzerland;F.HoffmanLaRocheLtd,Basel,Switzerland;F.Hoffmann-LaRoche,NewYork,NY;SeoulNationalUniversityHospital,Seoul,SouthKoreaAbstractDisclosures https://doi.org/10.1200/jco.2015.33.15_suppl.8008 Abstract Abstract8008Background:TheALKinhibitorcrizotinibisapprovedforpatients(pts)withALK-rearranged(ALK+)NSCLC,butmostptsprogresswithinayearandCNSprogressioniscommon.TheNP28673study(NCT01801111)investigatedtheefficacyandsafetyofalectinib,ahighlyselective,CNS-activeALKinhibitor,inALK+NSCLCptswhohadprogressedoncrizotinib.Methods:Eligiblepts(≥18yrs;locallyadvancedormetastaticALK+NSCLC[byFDA-approvedFISHtest];failedon/intoleranttocrizotinib)receivedalectinib600mgp.o.BIDuntilprogression,deathorwithdrawal.CrizotinibwastheonlypriorALKinhibitorpermitted.Primaryendpointwasobjectiveresponserate(ORR)byindependentreviewcommittee(IRC)usingRECISTv1.1.SecondaryendpointsincludedORRbyinvestigator;durationofresponse(DOR);CNSORRandDOR;progression-freesurvival(PFS);diseasecontrolrate(DCR),CNSprogressionrate,overallsurvival,andsafety.Results:138ptsfrom16countrieswereenrolledbythe18Aug2014cut-off.Medianage52yrs;80%hadpriorchemo;60%hadbaselineCNSmets(60/83treated).Medianfollow-upwas30wks.Intheresponse-evaluablepopulationassessedbyIRC(122ptswithmeasurablediseaseatbaseline),ORRwas49.2%(95%CI40.0–58.4;allPRs);DCRwas79.5%(95%CI71.3–86.3).Forpatientswithpriorchemoandcrizotinib(n=96),ORRwas43.8%(95%CI33.6–54.3);DCRwas78.1%(95%CI68.5–85.9).ForpatientswithbaselinemeasurableCNSdisease(n=34),IRC-assessedCNSORRwas55.9%(95%CI37.9–72.8),includingfiveCRs.UpdatedORR,DORandPFSdatawillbepresented.Overall,27.5%ofptshadgrade3–5adverseevents(AEs),mostcommonlydyspnea(3.6%)andpulmonaryembolism(2.2%);lowratesofdoseinterruptions(19.6%),reductions(8.7%),andwithdrawals(8.0%)duetoAEswereseen.Conclusions:Alectinibwaswelltoleratedandachievedarobusttreatmentresponse,includingexcellentintracranialactivity,inALK+NSCLCptswhohadprogressedoncrizotinib;mosthadalsofailedpriorchemoandhadCNSmets.Aphase3trialoffirst-linealectinibvscrizotinibandanexpandedaccessprogramareongoing.Clinicaltrialinformation:NCT01801111.©2015byAmericanSocietyofClinicalOncology OPTIONS&TOOLS ExportCitation TrackCitation AddToFavorites Rights&Permissions COMPANIONARTICLES Nocompanionarticles ARTICLECITATION DOI:10.1200/jco.2015.33.15_suppl.8008JournalofClinicalOncology 33,no. 15_suppl (May20,2015) 8008-8008. Publishedonline May20,2015.