免疫检查点阻断（ICB）与化疗相结合可改善转移性胃和胃食管交界处（G/GEJ）腺癌患者的预后；然而，这种组合在围手术期是否具有活性仍不清楚。旨在评估围手术期化疗和 ICB 继之以维持 ICB 在可切除 G/GEJ 腺癌中的安全性和初步活性。本研究由研究者发起、多中心、开放标签、单项研究2期非随机对照试验从2017年2月10日至2021年6月17日筛选了49名患者并入组了36名可切除的G/GEJ腺癌患者，中位（范围）随访时间为35.2（17.4-73.0）个月。 34 名患者被认为可进行疗效分析评估，其中 28 名患者（82.4%）接受了根治性切除。这项研究在美国 4 家转诊机构进行。患者接受 3 个周期的卡培他滨 625 mg/m2，每天口服两次，持续 21 天；奥沙利铂，130 mg/m2，静脉注射；帕博利珠单抗，200 mg，静脉注射，可选用表柔比星，50 mg/m2，手术前和手术后每 3 周一次，并在手术前额外使用一个周期的帕博利珠单抗。患者接受 14 次额外剂量的派姆单抗维持治疗。主要终点是病理完全缓解 (pCR) 率。次要终点包括总体缓解率、无病生存期 (DFS)、总体生存期 (OS) 和安全性。 共有 34 名患者（中位年龄 [范围]，65.5 [25-90] 岁；23 名患者 [67.6%]男性）可评估疗效。在这些患者中，28 例（82.4%）接受了根治性切除，7 例（20.6%；95% CI，10.1%-100%）实现了 pCR，6 例（17.6%）实现了病理接近完全缓解。在接受切除的 28 名患者中，4 名（14.3%）出现疾病复发。未达到中位 DFS 和 OS。 2 年 DFS 为 67.8%（95% CI，0.53%-0.87%），OS 为 80.6%（95% CI，0.68%-0.96%）。可评估患者中，20 名患者 (57.1%) 发生了与治疗相关的 3 级或以上不良事件，12 名患者 (34.3%) 经历了免疫相关的 3 级或以上不良事件。 在这项试验中，未选择的可切除 G/GEJ 腺癌患者、卡培他滨、奥沙利铂和派姆单抗的 pCR 率为 20.6%，且耐受性良好。该试验达到了主要终点，并支持在局部晚期 G/GEJ 腺癌中检查点抑制联合围手术期化疗的开发。ClinicalTrials.gov 标识符：NCT02918162。

Combining immune checkpoint blockade (ICB) with chemotherapy improves outcomes in patients with metastatic gastric and gastroesophageal junction (G/GEJ) adenocarcinoma; however, whether this combination has activity in the perioperative setting remains unknown.To evaluate the safety and preliminary activity of perioperative chemotherapy and ICB followed by maintenance ICB in resectable G/GEJ adenocarcinoma.This investigator-initiated, multicenter, open-label, single-stage, phase 2 nonrandomized controlled trial screened 49 patients and enrolled 36 patients with resectable G/GEJ adenocarcinoma from February 10, 2017, to June 17, 2021, with a median (range) follow-up of 35.2 (17.4-73.0) months. Thirty-four patients were deemed evaluable for efficacy analysis, with 28 (82.4%) undergoing curative resection. This study was performed at 4 referral institutions in the US.Patients received 3 cycles of capecitabine, 625 mg/m2, orally twice daily for 21 days; oxaliplatin, 130 mg/m2, intravenously and pembrolizumab, 200 mg, intravenously with optional epirubicin, 50 mg/m2, every 3 weeks before and after surgery with an additional cycle of pembrolizumab before surgery. Patients received 14 additional doses of maintenance pembrolizumab.The primary end point was pathologic complete response (pCR) rate. Secondary end points included overall response rate, disease-free survival (DFS), overall survival (OS), and safety.A total of 34 patients (median [range] age, 65.5 [25-90] years; 23 [67.6%] male) were evaluable for efficacy. Of these patients, 28 (82.4%) underwent curative resection, 7 (20.6%; 95% CI, 10.1%-100%) achieved pCR, and 6 (17.6%) achieved a pathologic near-complete response. Of the 28 patients who underwent resection, 4 (14.3%) experienced disease recurrence. The median DFS and OS were not reached. The 2-year DFS was 67.8% (95% CI, 0.53%-0.87%) and the OS was 80.6% (95% CI, 0.68%-0.96%). Treatment-related grade 3 or higher adverse events for evaluable patients occurred in 20 patients (57.1%), and 12 (34.3%) experienced immune-related grade 3 or higher adverse events.In this trial of unselected patients with resectable G/GEJ adenocarcinoma, capecitabine, oxaliplatin, and pembrolizumab resulted in a pCR rate of 20.6% and was well tolerated. This trial met its primary end point and supports the development of checkpoint inhibition in combination with perioperative chemotherapy in locally advanced G/GEJ adenocarcinoma.ClinicalTrials.gov Identifier: NCT02918162.