ASCO 2025：关键见解和创新 ASCO 2025 Key Insights and Innovations.docxVIP

ASCO2025:KeyInsightsandInnovations

HR+/HER2-BreastCancer

ThePhaseIIISERENA-6Trial

SERENA-6,snoveltrialdesignandctDNAstrategy

Approximately70%ofbreastcancersareER+/HER2-

ESR1mutationsactivateestrogenreceptor(ER)signaling,leadingtoendocrineresistance

ESR1mutationsarerareatdiagnosisbutemergein~40%ofpatientsafterprogressiononaromataseinhibitor(AI)+CDK4/6inhibitor(CDK4/6i)

AstraZeneca,scamizestrantisanext-generationoralSERDthatdegradesbothmutantandwild-typeER

SERENA-6isthefirstPhaseIIItrialtousectDNAtoguidepre-emptiveendocrinetherapyswitch

ctDNAcandetectESR1mutationsbeforeradiographicprogression

Trialdesign:SwitchfromAItocamizestrantuponESR1mutationdetection,continuingthesameCDK4/6i

Aim:Prolongefficacyoffirst-linetherapybyaddressingESR1-mediatedresistanceearlypriortoprogressiontosecond-linetherapy

Camizestrant’sefficacyandsafetyinSERENA-6

SwitchingAItocamizestrantwithcontinuationofCDK4/6isignificantlyimprovesprogression-freesurvival(PFS)

PFSbenefitwasconsistentacrosstheCDK4/6iandclinicallyrelevantsubgroups

Camizestrant+CDK4/6iwaswelltoleratedwithaverylowrateoftreatmentdiscontinuationsduetoadverseevents

Photopsiawasrare(Grade≥3in1%),non-disruptivetodailylife,andcausednostructuraleyedamage

Camizestrant+CDK4/6i

AI+CDK4/6

PValue/Hazardratio

MedianPFS

16.0months

9.2months

p0.00001/HR0.44(95%CI0.31–0.60)

PFSrateat12months

60.7%

33.4%

-

PFS2rateat12months(Informationfraction:54%)

85.4%

74.4%

-

Seriousadverseevents

10%

12%

-

Adverseeventleadingto

discontinuationofbothagents

1%

1%

-

SERENA-6:ContextandCompetitiveSERDLandscape

Innovativetrialdesign:Firststudytopre-emptivelyswitchtherapybasedonctDNA-detectedESR1mutationsduringfirst-linetreatment

Paradigmvalidation:Couldtransformtreatmentalgorithmsbyvalidatingbiomarker-basedt