K

KOLInsights

Topic:OvarianCancer

PhysicianInformation

Specialty:GynecologicalOncology

Location:US,Northeast

InterviewOVC11

TL#10173

May2025

2May2025Copyright?2025Citeline,aNorstellacompany(Unauthorizedphotocopyingprohibited)

KOLInsights:OvarianCancer

Highlights

Iwouldsayforwomenwithearly-stagedisease,qualityoflifeisrelativelygood.Imean,Iwouldsaythatthesurgerycanoftentimesbedonelaparoscopically.They'reusuallyrecoveringfromsurgerywithinfourtosixweeks,andthenthechemotherapyiseverythreeweeks,intravenous,mostofthemareabletohaveareasonableperformancestatusandqualityoflifeonchemo.Iwouldsayeverythreecycles,theyhaveaboutoneweekwherethey'renotfeelinggreat,andtheothertwoweeksthey'reactuallyfeelingrelativelyOK.Forthewomenthathaveadvancedstagedisease,itdependsontheirmedicalcomorbidities.So,whatothermedicalissuesdotheyhavethatmakethemmoreinfirm.It'salsolargelydependentonage.Obviously,theolderyouare,thelesswellyoudoonchemoandthelesswellyourecoverfromsurgery.So,Ithinkit'sdefinitelyharderforthewomenwithadvancedstagedisease.

Ithinkit'sunlikely[PD-1inhibitorswillbeapproved],justbasedonwhatweknowfromthepreliminarydatathatareavailable.Ithinkthatmaybeassingleagents,therearemoredatainendometrialcancerpatientsaroundtheimprovementinoverallsurvivalwithsingleagentpembrolizumaborKeytruda.So,IthinkmaybeifyouhadovariancancerthatoverexpressedPD-L1,asasingleagentitwouldmakesensetousethatdrug.ButwhenyoulookatthelikelihoodthatyouhaveatumorthatoverexpressesPD-L1forovariancancer,thenumbersarelike10-15%,it'sjustnotacommonmutation.

[…]Ithinkthatthis[avutometinib+defactinib]isbetterthanwehaveseenforanytreatmentinthisparticulargroupofwomen.Thebarhereisreallylowbecausethetreatmentsthatwe'reusingnow,whicharethesamethatweuseforhigh-gradeserousovariancancerjustdon'tworkinthistumor.So,thebarissolowthatIthinkifthosedataaresustained,evenifthefinaldataarealittlebitlessimpressivethantheyarenow,evenwiththat,Ithinkthatit'lllikelymoveforward,becausethebarinthisspaceissolow,becausewejustdon'thaveanythingthatworks.

Ithinkthatintheplatinum-resistantsetting,it'dbenicetohavedrugsthathadalongerresponserate,thathadhigherdurationofresponsebutalsohigherresponserates.Andthen,Ithinktheotherunmetneedisaroundcertainhistology,orcelltypesoftumors,wherewedon'thavealotofgreattreatment,andweusuallyextrapolatefromthetreatmentofhigh-gradeserousovariancancer.AndtheonesthatIwouldlistarealltheotherones,likelow-gradeseroushistology,wedon'thavegreattreatmentforrightnow.Ithinktheotheroneisclearcellcancers,wetendtotreatthemthesamewaythatwetreatovariancancer,butthosetreatmentsdon'tworkgreat.Mucinoustumors,Ithinkthere'salotofinterestinunderstandingwhetherthosetumorsshouldbetreatedmorewithGIorgastrointestinaltyperegimens.

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KOLInsights:OvarianCancer

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KOLInsights:OvarianCancer

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Let’sbeginwithyourtreatmentexperience.Canyoutalkaboutyourexperiencewithovariancancerandwhatsortofclinicalsettingyouworkin?

So,I’magynecologicaloncologist,board-certified,andI'vebeeninpracticefor25years.Ipracticeatanacademicmedicalcenter,andIsplitmytimeintheoutpatientsettingaswellastheoperatingroom.Iprobablydoabout500majorproceduresorsurgeriesayear,andIseesomewherebetween1,600-1,800ambulatorycarevisitsayear.Mostofmypatientsarewomenwithovarianorendometrialcancer.Typically,thosearethetwocancersthatIseethemostfrequently,justbasedontheincidenceofthosecancersintheUnitedStates.ButthenextsortofimportantcancerItreatiscervicalcancerandthenvulvarandvaginalcancer.

Whatstagesofovariancancerdoyounormallytreat?

Allstages.ThevastmajorityofwomencomeinwithstageIIIorIV.Iwouldsaythattypicallywhatyousee,notjustintheUnitedStates,butworldwide,becauseofthelackofeffectivescreening,onlyabout20%ofwomencomeinwitheitherstageIorII,andtheother80%willcomeinwithstageIIIorIVatdiagnosis.

DoyoutypicallytestforBRCA,HRDandfolatereceptor-α(FRα)?

Yes,atdifferenttimesinthecourseofsomebody'sdiagnosis.So,forBRCAgermlinetesting,thattestisdoneatdiagnosis.So,whenpatientscomeinandthey'rediagnosedwithovariancancer,theyarereferredtoageneticcounselor,andtheywillautomatically,iftheyagree,betestedforthegermlineBRCAmutation.Oncewehavetissueconfirmationoftheircancer,thetumorgetstestedforHRD,andthenforpatientsthathaverecurrentdiseaseoncethey'rebecomingplatinum-resistant,thentheirtumoristestedfortheoverexpressionofFRα.

Andwhatproportionofpatientswithearly-stagediseasegoontohavediseaserecurrence?

So,forstageI,it'smaybe5-10%,it'sreallyrare.Itdependsmostlyonthecelltypethanthestage,withclearcelltumorsbeingmorepronetorecurringormucinoustumorsbeingmorepronetorecurringthanserouscancers.ForstageII,it'sprobablyabout15%ofthosepatientsthatendupwithrecurrentdisease.

Stillthinkingabouttheseearly-stagepatients,whatpercentagewouldyousayexperiencelocalversusdistantprogressionofdisease?

Mostofthesepatientsdevelopdistantmetastaticdisease.Veryfewofthemwilldeveloplocalrecurrences.Typically,ovariancancerisnotconfinedtothepelvis;asyouknow,there'snoboundarybetweenthepelvisandtheabdomen,sothesepatientstendtodeveloprecurrentdiseasewithupperabdominaldisease,sonotnecessarilydistantmetastasistoalungorthebrain,butIwouldsaymetastaticdiseasetotheabdomen,whichisnotlocal.

Whatproportionofpatientswithadvanceddiseasegoontohaverecurrence?

So,forpatientswithstageIIIdisease,thepercentageis,Iwouldsay,about80%andforpatientswithstageIVdisease,closeto90%ofthemwilldeveloprecurrentdisease,ifnotallofthem.

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Andthenofthesepatients,whatproportionwouldtypicallygoontobecomeplatinumresistant?

So,allpatientswithovariancancer.Ultimatelythosewithadvanceddisease,theyalldevelopplatinum-resistantdisease.Itallstartstypicallyasplatinum-sensitivedisease,andusuallybythetimethey'regettingthird-linetreatment,mostofthesepatientshaveplatinum-resistantdisease.

So,wouldyousayallpatientsbecomeplatinum-sensitiveandthenplatinum-resistant,oraretherepatientswhobecomeplatinum-resistantwithoutbeingtreatedforplatinum-

sensitivedisease?

So,thenomenclatureisalittledifferent.Whenyou'refirstdiagnosedwithadvancedstagedisease,about5%ofpatientshaveplatinum-refractorydisease,meaningthattheyneverhadplatinum-sensitivedisease.Andthenofthe95%ofpatientsthatinitiallyhaveplatinumsensitivedisease,100%ofthosewomenwilldevelopplatinumresistantdiseaseatsomepoint.

Canyoutalkmethroughhowyouwouldtypicallytreatearly-stagepatients?

So,patientswithearly-stagediseasewillbetreatedwithsurgery.Thesurgeryisusuallyastagingprocedure,soformostpatients,andI'mgoingtoassumethatthesearenotpatientsthataregoingtowanttopreservefertility,they'llrequireahysterectomy,removalofbothovariesandfallopiantubes,removaloftheomentum,andthenapelvicandparaaorticlymphdissection.Thatprocedureallowsustonotonlyremovethecancer,butalsotostageit.Andthen,forwomenthathaveastagethat'sgreaterthanIa,typically,thosewomenwillrequireadjuvanttreatment.Thetreatmentthatweofferthemiscarboplatin-basedchemotherapy,sousuallythey'llreceiveaftersurgery,sixcyclesofcarboplatinandTaxol(paclitaxel),dependingontheriskofrecurrencethatmaybeaccompaniedbyAvastinmaintenancetherapy.AndthennotsomuchforwomenwithstageIdisease,butforwomenwithstageIIdisease,wewilllookatthegermlinegenetictestingfortheBRCAgene,aswellastheHRDtestingofthetumortoguidedecisionsaroundwhetherthosewomen,thatistheoneswithstageIIdisease,wouldbenefitfrombeingonamaintenancetherapywithaPARPinhibitor.So,thewomenwithstageIIdisease,uponcompletionofthesixcyclesofadjuvantchemowithcarboplatinandTaxol,iftheyhaveagermlinemutationintheBRCAgenome,theyhavetumorsthatareHRD-deficient,willbeofferedtwoyearsofmaintenancetherapy,usuallywitholaparib(Lynparza).

Andcouldyouestimatetheproportionoftheseearly-stagepatientswhoreceivepharmacologicaltreatment?

Thosethatreceivechemotherapy?

Yes,chemotherapyandanykindoftreatment,adjuvanttreatmentwithchemotherapyoradjuvanttreatmentthenmaintenancetherapy.

So,Ijustwanttomakesurethatwehavethesamenomenclature.So,forusintheUnitedStates,adjuvanttreatmentistreatmentaftersurgery,soit'sbasicallyfirst-linechemo.So,Iwouldsayabout90%ofthesepatientswillendupreceivingsomekindofadjuvantchemotherapy,andabout40%ofthemwillreceiveadjuvantchemotherapyplusmaintenancetherapy.

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Doyoutypicallyseeanyearly-stagepatientsthatgostraightintoclinicaltrials?

Notusually,no.Mostclinicaltrialsthatwerunareusuallyforwomenwithrecurrentdisease.ThetrialsthatwouldbeappropriateinthatsettingforthosepatientswouldbeonesthataretryingtoidentifybettertherapiesthancarboplatinandTaxol.AndthelasttrialsthatraninthatplatformwereICON7andGOG-218andtheywereforwomenwithadvancedstagedisease.

Andstillontheearly-stagepatients,arethereanypatientsthatreceivepharmacologicaltreatmentswithoutsurgery?

No,becausethestagingofthecancerisactuallysurgery.So,typicallyforwomenthathaveearly-stagedisease,theyhaveaveryhighcurerate,soyouwouldnevernotofferthemsurgery.Therearewomenwhoarevery,veryyoungwhowanttopursuefertilitywheretheywouldnotgetthefullhysterectomy,andremovalofthecontralateralovary,buttheywouldstillgettheovarywiththetumorremoved,aswellasthelymphnodesandtheomentectomyperformed.

Movingtotheadvanced-stagepatients,howmanyofthemwouldbefittohavesurgery?

Iwouldsayabout90%ofthemarefitenoughtohavesurgery.Thechallengeforus,orthedistinctionthatwemake,iswhenthatoperationisdone.So,ifyoutakethe90outof100womenthatwillultimatelyhavesurgery,about45%ofthemwillhavesurgeryupfront,andthey'llhavechemoafterthat.Theother55%willhaveinductionchemotherapyorneoadjuvantchemotherapy,thenthey'llhavesurgery,andthenthey'llhavemorechemotherapyaftersurgery.

Andoverall,howwouldyoutypicallytreatadenovo,advancedstagecase?

Thefirstthingthatwedoistrytodelineatethevolumeofdiseaseandthelocationofthetumor,totrytoascertainwhetherwecanresectallofitupfront.Thegoalofsurgeryatalltimesistoremoveallthecancer,ifthat'spossible,oratleastdowhat'scalledanoptimalcytoreductivesurgery,whichmeansthatwedon'twanttoleaveanydiseasenodulesthataregreaterthanacentimeterindiameterbehind.Weknowthatifwearenotabletoachieveatleastanoptimalprocedure,patientsarenotaffordedanybenefittosurgery.So,thealgorithm,theinitialdecision-makingisaroundwhetherthispatientissomebodywhosetumorcanberesectedcompletely,oratleastinanoptimalfashionupfront.Thatrepresentsabout45%ofpatients,so,thosepatientswillundergosurgicalresectionfirst,andthenoncetheyrecoverfromsurgery,usuallywithinamonthoftheoperation,they'rereceivingsixcyclesofcarboplatinandTaxolwithorwithoutAvastin,andthenagain,dependingontheirgenetictestingandtheHRDstatusofthetumor,they'llbetriagedtomaintenancetherapywithaPARPinhibitororwithAvastiniftheydon'thavetheBRCAgermlinemutationorifthetumorisnotHRD-deficient.Forthewomenwhoarenotsurgicalcandidatesupfront,andthat'sbecauseeitherthedistributionofdiseaseisnotresectableupfront,orthey'remedicallytooinfirmtohavesurgery,they'llbetriagedtothreecyclesofchemotherapy,thenwe'llscanthemagaintomakesurethattheyhaveresectablediseaseatthattimepoint.Mostofthosewomenhaveresectablediseaseafterthreecyclesofchemo,thenthey'llgotosurgery,andthenaftertheoperation,they'llgettheadditionalthreecyclesofchemo,andthenwe'llmakethesamedecisionsaroundwhetherornottheywouldbeeligibleformaintenancewithaPARPinhibitororpotentiallymaintenancetherapywithAvastin.

Andcanyoutalktomeaboutthequalityoflifeofthesepatientsaftertreatment?

Iwouldsayforwomenwithearly-stagedisease,qualityoflifeisrelativelygood.Imean,Iwouldsaythatthesurgerycanoftentimesbedonelaparoscopically.They'reusuallyrecoveringfromsurgerywithinfourtosixweeks,andthen

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thechemotherapyiseverythreeweeks,intravenous,mostofthemareabletohaveareasonableperformancestatusandqualityoflifeonchemo.Iwouldsayeverythreecycles,theyhaveaboutoneweekwherethey'renotfeelinggreat,andtheothertwoweeksthey'reactuallyfeelingrelativelyOK.Forthewomenthathaveadvancedstagedisease,itdependsontheirmedicalcomorbidities.So,whatothermedicalissuesdotheyhavethatmakethemmoreinfirm.It'salsolargelydependentonage.Obviously,theolderyouare,thelesswellyoudoonchemoandthelesswellyourecoverfromsurgery.So,Ithinkit'sdefinitelyharderforthewomenwithadvancedstagedisease.Also,theytendtocomeinwithmanysymptomsofovariancancer,likeweightloss,cachexia,nausea,vomiting,diarrhea,constipation;they'relosingweight.They'renotfeelinggreat.Theytendtostartfeelingbetterfromthecancersymptomsonchemobutobviouslywhattheyenduphavingischemotherapy-relatedsideeffects.So,forthepatientswithadvancedstagedisease,qualityoflifeisdefinitelymoreonthefairside.Insteadoftwoweeksoutofthethreebeingreasonableweeks,theytypicallyhaveonereasonableweekandtwoweekswherethey'reontheirchemotherapyscheduleorthey'renotfeelinggreat.

Canyoutalkmethroughhowyouwouldtreatapatientwithrecurrentplatinum-sensitivedisease?

So,thosepatientstodaywillgetaplatinum-baseddoublet.Typically,they'llgetcarboplatinagain,butinsteadofgettingTaxolwithit,theyusuallygetDoxil(doxorubicin)withorwithoutAvastin(bevacizumab).Andtypically,wetreatforatleastthreecyclesandasmanyassix,andatthatpointtheycanbeofferedmaintenancetherapywithAvastin,ortheycanpotentiallygoonabreak.TheothertwoplatinumdoubletsthatwouldbeavailabletothemarecarboplatinandTaxolorcarboplatinandgemcitabine,buttheothertwodoubletstendtobemoretoxic,soweusuallyfavorthecarboplatin,Doxil-baseddoublet.

Andthisisirrespectiveofthepatient'sBRCAstatus?

Usually,yes.Imean,iftheyhaveaBRCAmutation,theymaygoonaPARPinhibitorformaintenancetherapyiftheyhaven'thadaPARPinhibitorbefore.ButwhatweseenowisthatbecausePARPshavebeenapprovedforseveralyearsnow,mostwomenwhodevelopplatinum-sensitivediseasethatwouldbeeligibleforaPARPinhibitor,havealreadyreceivedthatasmaintenancetherapyintheupfrontsetting.

Andhowwouldyoutreatpatientswithrecurringplatinum-resistantovariancancer?

So,withplatinum-resistantdisease,thefirstthingIdoisIcheckfortheFRαoverexpressioninthetumor.IfthetumorhasahighoverexpressionoftheFRα,thenthatpatientinmypracticewouldbeofferedmirvetuximab(Elahere).Weoftentimeslookatclinicaltrialstoseeifthereareclinicaltrialsthatwouldbeopentothem,andthentheyarenotcandidatesformirvetuximab,orthey'vealreadyhadmirvetuximab,andwedon'thaveanyclinicaltrialsavailabletothem,thenusuallywetreatthemwithTaxolandAvastindoublet,basedontheAURELIAtrial.Andthen,oncetheyhavebeenexposedtothat,andtheycontinuetohaveprogressionofdisease,assumingthatthey'restilleligibleforchemo,they'retypicallynowgettingsingleagenttherapy,andthedrugsthatweuseinthatsettingwouldbetopotecanorHycamtin,gemcitabine,Alimta(pemetrexed).So,nowwe'reessentiallyjusttryingtomitigate,gettostablediseaseifwecanorslowprogression.Butresponseratesinthatsettingareusuallyaround10-15%,soit'snotgreat.

Andwhatcanyoutellmeaboutthequalityoflifeinthesepatients?

Iwouldsayrelativelypoorbythattime;theyobviouslyhavethesideeffectsofthetreatmentthatthey'rereceiving.Butasyoucanimagine,thefurtheryouareintoyourlinesoftherapy,themoresymptomaticyou'vebecome,both

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fromhavingcumulativesideeffectsoftherapyandalsofromthecancerburden.Forthemostpart,thesepatientswillhaveaseriesofsideeffectsthatarerelatedtothetreatmentthatthey'rereceiving,andthenaseriesofsideeffectsthattheyhavefromchemo,fatigue,somenausea,someconstipation,weightloss,lossofappetite,soanorexia,weakness,overfatigue,certainlymostofthemhavesomeformofneuropathy.So,Iwouldsayqualityoflifeisrelativelypoor.

ForpatientswithBRCAwild-typedisease,howwouldyoutypicallytreatthem?

So,they'retreatedjustasIhaveoutlined,exceptthatthey'renotgoingtoreceiveaPARPinhibitor.So,forupfrontdisease,theywillgetsurgery,eitherupfrontorintheintervalsetting,they'llgetcarboplatinandTaxol.ThesepatientstodayintheUnitedStatesareusuallyaskingforAvastin,concurringwithchemoandthenasmaintenancetherapy,mostlybecausetheyarequiteupsetthatthey'renoteligibletoreceiveaPARPinhibitorformaintenance,andtheydon'twanttogoontobasicallyjustbewatchedafterthey'vecompletedtreatment,andsoevenafteryouexplaintothemthattherearenosurvivaladvantagestoreceivingconcurrentAvastinwithchemoandthenayearofAvastinmaintenance,theonlybenefitisafour-monthprogressionfreesurvivaladvantage,butagain,nodifferenceinoverallsurvival,theystillpreferthatoptionthantheoptionofjustsurveillanceaftercompletingchemotherapy.So,they'retreatedjustthesame,exceptthatthey'renotgoingtogetaPARPinhibitorever,andtheyaremorelikelytoreceiveAvastinwithchemotherapyupfrontandthenayearofAvastinformaintenancetherapy.

Overall,whatpercentageofpatientswouldyousayreceiveAvastininthefirst-linesetting?

Iwouldsayprobablyabout35-40%andthat'sbasedonifyousubtractfrom100patientswhocouldpotentiallybeeligibleforthatdiscussion’ssake,let'ssayabout50%ofthemaregoingtobeeligibleforaPARPinhibitor,10%ofthemarenotgoingtowantAvastinortheyhavecontraindicationstoreceivingAvastin,andtheother40%arewomenthatarenotBRCAgermlinepositive.TheyhavetumorsthatareHRD-proficient,andtheywanttogoonAvastinoverjustclosesurveillance.

SpeakingabouttheeligibilitytoreceiveAvastin,oneofthereasons,Isuppose,wouldbebecauseoftheblackboxwarning?

Yes,sothecontraindicationsincludeanybodywitharecentclottingevent,womenthathaveuncontrolledhypertension,they'rerare,butcertainly,Iwouldsaysomebodywho'sreallyoldandfrail,whereyouwereworriedthatimmobilitywouldmakethemmorepronetoclottingorstroking,you'dbecarefulintermsofrecommendingit.Butthat'swhyIthinkthepercentagethereisnotveryhigh.There'snotalotofwomenwhoarenoteligibleforit.

AndwhatpercentageofpatientsareonAvastinversusbiosimilarbevacizumab?

Inourhospital,weusuallytreateverybodywiththebiosimilaroption,that'sjustbasedonourformularypreference,unlessapatientistryingthebiosimilar,andforsomereasontheyhaveareaction,whichIhaven'tseeninmypractice,butwetypicallyheregivethebiosimilaralternative.

Howoftendoyouprescribeolaparibasfirstlinemaintenance?

FortherightpatientswhoareeligibleforaPARPinhibitor,ItypicallyuseolaparibovertheothertwoPARPinhibitors;rucaparib(Rubraca)isnotapprovedasfirstlinemaintenancetherapy,andZejula(niraparib),wehavelessexperiencewithalthoughit'sbeenaroundforawhile.Ithinkthatmostofusgotusedtousingolaparib,soIfindit'seasierto

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dose-reducepatientsonolaparib,easiertodealwiththeinsurancecompany.Theoneexclusiontothatisthatforpatientswhodon'thavetheBRCAmutation,whohavetumorsthatareHRD-proficient,whoreallyinsistonwantingtobeonaPARPinhibitor,asyouknowZejulahasdatathatthereissomebenefitaroundprogressionfreesurvivalforthosepatients.So,let’ssaythepatientisineligibleforaPARPinhibitorwitholaparib,butwantstobeonaPARPinhibitor,thentypically,IwilluseZejulainthatsetting,becausethat'stheonePARPinhibitorthat'sapprovedforthosewomen.

AndcouldyoupotentiallyestimatewhatproportionwouldwanttohaveZejula?

Theproportionthereisprobablyabout10%.

SwitchingtomirvetuximabspecificallyforpatientswhoareFRα-positive,inwhatsettingsdoyoucurrentlyusethedrug?

Iuseitveryearlyintheplatinum-resistantrecurrentsetting.So,onceIknowthatsomebodyisheadingthatway,meaningthattheirplatinum-freeintervalislikelytobelessthansixmonths,I'llgoaheadandcheckthetumorforoverexpressionofFRα.AndthereasonthatIweighthatlateisthatintheUnitedStates,youcannotgetapprovalforthetesttoberununlesspatientshaveplatinum-resistantdisease.ButItrytogiveitearlyon,intheplatinum-resistantsetting,asasingledrug;itistheonlydrugassociatedwithanimprovementinoverallsurvival,andtheresponseratesarearound44-45%,soitisthebestdrugthatwehave,it'sjustthatnoteverybodyiseligibleforit.So,Itypicallygiveitinthatsetting,itisgoingtobethird-linetherapy,fourthline,butit'sthefirsttreatmentthatIofferpatientswhoareeligibleforit,assoonastheydevelopplatinumresistantdisease.

Andcouldyouestimateproportion-wise,howmanypatientsaretreatedwithmirvetuximab?

Ithinkinmypracticeitissomewherebetween35-40%ofpatientswithplatinum-resistantdiseasewhohavehighoverexpressionoftheFRα.

Andmirvetuximabisalsobeingassessedincombinationwithbevacizumabas

maintenanceinpatientswithplatinum-sensitiveovarianc