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Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction

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dc.contributor.authorZhu, Mojun
dc.contributor.authorChen, Chunhua
dc.contributor.authorFoster, Nathan
dc.contributor.authorHartley, Christopher
dc.contributor.authorMounajjed, Taofic
dc.contributor.authorSalomao, Marcela
dc.contributor.authorFruth, Briant
dc.contributor.authorBeamer, Staci
dc.contributor.authorKim, Yohan
dc.contributor.authorHarrington, Susan
dc.contributor.authorPitot, Henry
dc.contributor.authorSanhueza, Cristobal
dc.contributor.authorFeng, Yening
dc.contributor.authorHerrmann, Joerg
dc.contributor.authorMcWilliams, Robert
dc.contributor.authorLucien, Fabrice
dc.contributor.authorHuang, Bing
dc.contributor.authorWee, Wen
dc.contributor.authorBekaii, Tanios
dc.contributor.authorDong, Haidong
dc.contributor.authorWigle, Dennis
dc.contributor.authorAhn, Daniel
dc.contributor.authorHallemeier, Chris
dc.contributor.authorBlackmon, Shanda
dc.contributor.authorYoon, Harry
dc.date.accessioned2024-06-12T18:46:17Z
dc.date.available2024-06-12T18:46:17Z
dc.date.issued2022
dc.description.abstractPurpose: This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma. Patients and methods: Patients with GEJ adenocarcinoma (cT1-3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)]. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma. Results: We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met [7/31 (22.6%) achieved pCR]. Patients with high [i.e., combined positive score (CPS) ≥ 10] baseline expression of programmed death (PD)-L1 in the TME had a significantly higher pCR rate than those with low expression [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS < 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level of PD-L1-expressing EVs was significantly associated with higher pCR. Conclusions: Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.
dc.description.versionPublicada
dc.identifier.citationZhu M, Chen C, Foster NR, Hartley C, Mounajjed T, Salomao MA, Fruth BF, Beamer SE, Kim Y, Harrington SM, Pitot HC, Sanhueza CT, Feng Y, Herrmann J, McWilliams RR, Lucien F, Huang BQ, Ma WW, Bekaii-Saab TS, Dong H, Wigle D, Ahn DH, Hallemeier CL, Blackmon S, Yoon HH. Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction. Clin Cancer Res. 2022 Jul 15;28(14):3021-3031. doi: 10.1158/1078-0432.CCR-22-0413
dc.identifier.doihttps://doi.org/10.1158/1078-0432.CCR-22-0413
dc.identifier.urihttps://hdl.handle.net/11447/9084
dc.language.isoen
dc.subjectAdenocarcinoma drug therapy
dc.subjectAntibodies
dc.subjectMonoclonal
dc.subjectHumanized
dc.subjectB7-H1 Antigen metabolism
dc.subjectEsophagogastric Junction pathology
dc.subjectNeoadjuvant Therapy
dc.subjectEsophageal Neoplasms
dc.subjectTumor Microenvironment
dc.titlePembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceClinical cancer research : an official journal of the American Association for Cancer Research
dspace.entity.typePublication

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