Browsing by Author "Zhu, Mojun"
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Publication Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction(2022) Zhu, Mojun; Chen, Chunhua; Foster, Nathan; Hartley, Christopher; Mounajjed, Taofic; Salomao, Marcela; Fruth, Briant; Beamer, Staci; Kim, Yohan; Harrington, Susan; Pitot, Henry; Sanhueza, Cristobal; Feng, Yening; Herrmann, Joerg; McWilliams, Robert; Lucien, Fabrice; Huang, Bing; Wee, Wen; Bekaii, Tanios; Dong, Haidong; Wigle, Dennis; Ahn, Daniel; Hallemeier, Chris; Blackmon, Shanda; Yoon, HarryPurpose: 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.