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A phase 2 evaluation of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability.

Stefania BelloneDana M RoqueEric R SiegelNatalia BuzaPei HuiElena BonazzoliAdele GuglielmiLuca ZammataroNupur NagarkattiSamir ZaidiJungsoo LeeDan-Arin SilasiGloria Shining HuangVaagn AndikyanShari DamastMitchell ClarkMasoud AzodiPeter E SchwartzJoan R Tymon-RosarioJustin A HaroldDennis MauricioBurak ZeybekGulden MenderesGary AltwergerElena RatnerLudmil B AlexandrovAkiko IwasakiYong KongEric SongWeilai DongJulia A ElvinJungmin ChoiAlessandro D Santin
Published in: Cancer (2021)
This study suggests prognostic significance of Lynch-like cancers versus sporadic MSI-H/dMMR ECs for ORR, PFS, and OS when patients are treated with pembrolizumab. Larger confirmatory studies in ECs and other MSI-H/dMMR tumors are necessary. Defective antigen processing/presentation and deranged induction in interferon responses serve as mechanisms of resistance in sporadic MSI-H ECs. Oligoprogression in MSI-H/dMMR patients appears salvageable with surgical resection and/or local treatment and the continuation of pembrolizumab off study. Clinical studies evaluating separate MSI-H/dMMR EC subtypes treated with ICIs are warranted.
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