目的：观察卡瑞利珠单抗联合奥沙利铂和替吉奥在局部晚期或转移性胃/胃食管交界癌（G/GEJC）一线治疗中的疗效及安全性。方法：选择我院收治的77例人类表皮生长因子受体2（HER-2）阴性的局部晚期或转移性G/GEJC患者为研究对象，以奥沙利铂和替吉奥方案化疗的45例患者为对照组，以卡瑞利珠单抗联合奥沙利铂和替吉奥方案化疗的32例患者为观察组。比较两组患者的客观缓解率（ORR）、疾病控制率（DCR）、中位无进展生存期（mPFS）及不良反应发生情况；采用Kaplan-Meier生存曲线及Cox风险比例回归模型探索影响患者无进展生存期（PFS）的相关因素。结果：观察组ORR、DCR均高于对照组（62.5%vs.53.3%、81.3% vs.77.8%），但差异无统计学意义（P>0.05）；观察组mPFS 8.7个月（95%CI 6.8~10.6）较对照组mPFS 5.8个月（95%CI 4.4~7.1）明显延长，差异具有统计学意义（χ²=6.499，P=0.011）；单因素和多因素Cox回归分析显示：转移灶数量、中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）与患者PFS有关，且NLR值是影响患者PFS的独立危险因素。安全性方面：与对照组相比，观察组出现了12例反应性毛细血管增生症（RCCEP），差异具有统计学意义（P<0.05）；而两组其它不良反应发生情况差异无统计学意义（P>0.05），且多数不良反应为1~2级，两组患者均未发生与治疗相关的死亡事件。结论：卡瑞利珠单抗联合奥沙利铂和替吉奥在局部晚期或转移性G/GEJC一线治疗中显示出良好的疗效及可控的安全性。

[1] SONG Z, WU Y, YANG J, et al.Progress in the treatment of advanced gastric cancer[J].Tumour Biol, 2017, 39(7):1010428317714626.
[2] ZHANG M, LI Z, MA Y, et al.Prognostic predictors of patients with carcinoma of the gastric cardia[J].Hepatogastroenterology, 2012, 59(115):930-933.
[3] HUANG D, LU N, FAN Q, et al.Her2 status in gastric and gastroesophageal junction cancer assessed by local and central laboratories:Chinese results of the HER-EAGLE study[J].PLoS One, 2013, 8(11):e80290.
[4] MURO K, VAN CUTSEM E, NARITA Y, et al.Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer:a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS[J].Ann Oncol, 2019, 30(1):19-33.
[5] KITO Y, MACHIDA N, KAWAI S, et al.Phase II study of S-1 plus oxaliplatin 130 mg/m(2) in Japanese patients with advanced gastric cancer[J].Int J Clin Oncol, 2018, 23(6):1084-1089.
[6] KASHIWADA T, SHINOZAKI K, UENO S, et al.Safety and efficacy of S-1 plus oxaliplatin 130 mg/m(2) combination therapy in patients with previously untreated her2-negative unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer:a phase II trial (KSCC1501A)[J].Int J Clin Oncol, 2021, 26(2):345-354.
[7] GANDHI L, RODRÍGUEZ-ABREU D, GADGEEL S, et al.Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer[J].N Engl J Med, 2018, 378(22):2078-2092.
[8] RINI B I, PLIMACK E R, STUS V, et al.Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma[J].N Engl J Med, 2019, 380(12):1116-1127.
[9] ROUANNE M, ROUMIGUIÉ M, HOUÉDÉ N, et al.Development of immunotherapy in bladder cancer:present and future on targeting pd(l)1 and CTLA-4 pathways[J].World J Urol, 2018, 36(11):1727-1740.
[10] EISENHAUER E A, THERASSE P, BOGAERTS J, et al.New response evaluation criteria in solid tumours:revised RECIST guideline (version 1.1)[J].Eur J Cancer, 2009, 45(2):228-234
[11] 皋文君, 刘砚燕, 袁长蓉.国际肿瘤化疗药物不良反应评价系统——通用不良反应术语标准4.0版[J].肿瘤, 2012, 32(2):142-144.
[12] AJANI J A, D'AMICO T A, BENTREM D J, et al.Gastric Cancer, Version 2.2022, NCCN clinical Practice guidelines in oncology[J].J Natl Compr Canc Netw, 2022, 20(2):167-192.
[13] KANG Y K, BOKU N, SATOH T, et al.Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2):a randomised, double-blind, placebo-controlled, phase 3 trial[J].Lancet, 2017, 390(10111):2461-2471.
[14] FUCHS C S, DOI T, JANG R W, et al.Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer:phase 2 clinical KEYNOTE-059 trial[J].JAMA Oncol, 2018, 4(5):e180013.
[15] PENG Z, WEI J, WANG F, et al.Camrelizumab combined with chemotherapy followed by camrelizumab plus apatinib as first-line therapy for advanced gastric or gastroesophageal junction adenocarcinoma[J].Clin Cancer Res, 2021, 27(11):3069-3078.
[16] ZITVOGEL L, GALLUZZI L, SMYTH M J, et al.Mechanism of action of conventional and targeted anticancer therapies:reinstating immunosurveillance[J].Immunity, 2013, 39(1):74-88.
[17] BOKU N, RYU M H, KATO K, et al.Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer:interim results of a randomized, phase II trial (ATTRACTION-4)[J].Ann Oncol, 2019, 30(2):250-258.
[18] KAWAZOE A, YAMAGUCHI K, YASUI H, et al.Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer:cohort 1 data from the KEYNOTE-659 phase IIb study[J].Eur J Cancer, 2020, 129:97-106.
[19] JANJIGIAN Y Y, SHITARA K, MOEHLER M, et al.First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649):a randomised, open-label, phase 3 trial[J].Lancet, 2021, 398(10294):27-40.
[20] BORSIG L, WOLF M J, ROBLEK M, et al.Inflammatory chemokines and metastasis——tracing the accessory[J].Oncogene, 2014, 33(25):3217-3224.
[21] FENG F, SUN L, ZHENG G, et al.Low lymphocyte-to-white blood cell ratio and high monocyte-to-white blood cell ratio predict poor prognosis in gastric cancer[J].Oncotarget, 2017, 8(3):5281-5291.
[22] CHO I R, PARK J C, PARK C H, et al.Pre-treatment neutrophil to lymphocyte ratio as a prognostic marker to predict chemotherapeutic response and survival outcomes in metastatic advanced gastric cancer[J].Gastric Cancer, 2014, 17(4):703-710.
[23] WANG H, DING Y, LI N, et al.Prognostic value of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and combined neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in stage IV advanced gastric cancer[J].Front Oncol, 2020, 10:841.
[24] WEBER J S, D'ANGELO S P, MINOR D, et al.Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037):a randomised, controlled, open-label, phase 3 trial[J].Lancet Oncol, 2015, 16(4):375-384.
[25] CHEN X, MA L, WANG X, et al.Reactive capillary hemangiomas:a novel dermatologic toxicity following anti-pd-1 treatment with SHR-1210[J].Cancer Biol Med, 2019, 16(1):173-181.