派姆单抗在错配修复缺陷型结直肠癌中治疗前景.pdfVIP

PembrolizumabShows

PromisingActivityinMismatch

Repair–DeficientCRC

CCOtConferenceCoverage*

ofthe2016ASCOAnnualMeeting,June3-7,2016

*CCOisantmedicaleducationcompanythatprovidesstate-of-the-artmedical

informationtohealthcareprofessionalsthroughconferencecoverageandothereducationalprograms.

ThisactivityissupportedbyeducationalgrantsfromAmgen,Ariad,

BayerHealthcarePharmaceuticals,CelgeneCorporation,Genentech,

Incyte,Merck,andTaihoPharmaceuticals.

PembrolizumabinMismatchRepair–

DeficientCRC:Overview

▪MismatchrepairdefectsleadtoMSI-H

–MSI-Hassociatedwithhereditarynonpolyposiscolorectalcarcinomaand

presentin15%ofCRCsacrossallstages

–MSI-Htumorsharborgeneticmutationsthatarepotentiallyrecognizable

byimmunesystem;abundantexpressionofneoontumorcells

createsinflamedmicroenvironmentwithhighexpressionofimmune

checkpoints,suchasPD-1

▪PD-1blockadehasantitumoreffectsinMSI-Htumors

▪Pembrolizumab,animmunecheckpointinhibitorofPD-1,evaluatedin

ptswithtreatment-refractory,progressive,metastaticcancerby

mismatchrepairstatus[1]

–Receivedbreakthroughtherapydesignationin11/2015fortxofMSI-H

CRC

▪CurrentreportsummarizesphaseIdataonPD-1blockadewith

pembrolizumabinptswithmismatchrepair–deficientCRC[2]

1.LeDT,etal.NEnglJMed.2015;372:2509-2520.

2.LeDT,etal.ASCO2016.103.Slidecredit:

PembrolizumabinMismatchRepair–

DeficientCRC:StudyDesign

▪EligibilityforcohortsAandB:

–Histologicallyconfirmedmetastaticorlocally

advancedCRC,withorwithoutmismatchrepairCohortA(n28)

deficiencyMMRDC