PMID- 35720388 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20220716 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Neoadjuvant Pembrolizumab and Chemotherapy in Resectable Esophageal Cancer: An Open-Label, Single-Arm Study (PEN-ICE). PG - 849984 LID - 10.3389/fimmu.2022.849984 [doi] LID - 849984 AB - BACKGROUND: In this single-arm study, the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy were evaluated in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: This study included patients with ESCC of clinical stages II-IVA who underwent surgery within 4 to 6 weeks after completing treatment with pembrolizumab (200 mg) combined with a conventional chemotherapy regimen (3 cycles). The safety and efficacy of this combination treatment were evaluated as primary endpoints of the study. RESULTS: From April 2019 to August 2020, a total of 18 patients (including 14 men) were enrolled, of whom 13 patients progressed to surgery. Postoperative pathology revealed a major pathological response (MPR) in 9 cases (9/13, 69.2%) and a pathological complete response (pCR) in 6 cases (6/13, 46.2%). Five patients (5/18, 27.8%) experienced serious treatment-related adverse events (AEs) of grades 3-4. At the time of data cutoff (Mar 25, 2022), the shortest duration of follow-up was 17.8 months. Programmed death-ligand 1 (PD-L1) expression in pretreatment specimens was not significantly associated with the percentage of residual viable tumor (RVT) (r=-0.55, P=0.08). Changes in counts of CD68(+) macrophage between pre- and post-treatment specimens were weakly correlated with RVT (r=0.71; P=0.07), while a positive correlation was observed between postoperative forkhead box P3-positive (Foxp3)(+)T cells/CD4(+)Tcells ratios and RVT (r=0.84, P=0.03). CONCLUSIONS: The combination of neoadjuvant immunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment (TME). It has acceptable toxicity and great efficacy, suggesting a strong rationale for its further evaluation in randomized clinical trials (RCTs). TRIAL REGISTRATION: ChiCTR2100048917. CI - Copyright (c) 2022 Duan, Shao, Pan, Liu, Dong, Zhang, Tong, Feng, Wang, Wang, Newman, Sarkaria, Reynolds, De Cobelli, Ma, Jiang and Yan. FAU - Duan, Hongtao AU - Duan H AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Shao, Changjian AU - Shao C AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Pan, Minghong AU - Pan M AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Liu, Honggang AU - Liu H AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Dong, Xiaoping AU - Dong X AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Zhang, Yong AU - Zhang Y AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Tong, Liping AU - Tong L AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Feng, Yingtong AU - Feng Y AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Wang, Yuanyuan AU - Wang Y AD - Department of Pathology, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Wang, Lu AU - Wang L AD - Department of Pathology, Xijing Hospital, Air Force Medical University, Xi'an, China. FAU - Newman, Neil B AU - Newman NB AD - Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States. FAU - Sarkaria, Inderpal S AU - Sarkaria IS AD - Department of Cardiothoracic Surgery, The University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center, Pittsburgh, PA, United States. FAU - Reynolds, John V AU - Reynolds JV AD - Department of Surgery, Trinity Centre, St. James's Hospital, Dublin, Ireland. FAU - De Cobelli, Francesco AU - De Cobelli F AD - Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Ma, Zhiqiang AU - Ma Z AD - Department of Medical Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China. FAU - Jiang, Tao AU - Jiang T AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Yan, Xiaolong AU - Yan X AD - Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. LA - eng SI - ChiCTR/ChiCTR2100048917 PT - Clinical Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220602 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies, Monoclonal, Humanized) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Antibodies, Monoclonal, Humanized/therapeutic use MH - *Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - *Esophageal Neoplasms/drug therapy MH - *Esophageal Squamous Cell Carcinoma/drug therapy MH - Female MH - Humans MH - Male MH - Neoadjuvant Therapy MH - Tumor Microenvironment PMC - PMC9202755 OTO - NOTNLM OT - Pembrolizumab OT - chemotherapy OT - efficacy OT - major pathological response (MPR) OT - pathological complete response (pCR) OT - resectable esophageal cancer OT - safety COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/06/21 06:00 MHDA- 2022/06/22 06:00 PMCR- 2022/01/01 CRDT- 2022/06/20 03:42 PHST- 2022/01/06 00:00 [received] PHST- 2022/04/28 00:00 [accepted] PHST- 2022/06/20 03:42 [entrez] PHST- 2022/06/21 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.849984 [doi] PST - epublish SO - Front Immunol. 2022 Jun 2;13:849984. doi: 10.3389/fimmu.2022.849984. eCollection 2022.