基于PD-L1蛋白表达水平的胃癌免疫治疗专家共识(2023年版)

中国抗癌协会胃癌专业委员会

中国抗癌协会胃癌专业委员会. 基于PD-L1蛋白表达水平的胃癌免疫治疗专家共识(2023年版)[J]. 中国肿瘤临床. doi: 10.12354/j.issn.1000-8179.2023.20231335
引用本文: 中国抗癌协会胃癌专业委员会. 基于PD-L1蛋白表达水平的胃癌免疫治疗专家共识(2023年版)[J]. 中国肿瘤临床. doi: 10.12354/j.issn.1000-8179.2023.20231335

基于PD-L1蛋白表达水平的胃癌免疫治疗专家共识(2023年版)

doi: 10.12354/j.issn.1000-8179.2023.20231335
详细信息
    通讯作者:

    梁寒 Email:tjlianghan@126.com;朱正纲 Email:ZZG1954@hotmail.com;张艳桥 Email:yanqiaozhang@126.com

  • 摘要: 以程序性死亡蛋白-1(programmed death protein-1,PD-1)抑制剂为代表的免疫检查点抑制剂在胃癌中显示良好疗效,逐渐改变晚期胃癌的治疗格局。多项研究表明,对于程序性死亡蛋白配体-1(programmed death ligand-1,PD-L1)高表达的患者,PD-L1单抗的治疗效果更为优异,且与PD-L1蛋白表达水平呈正相关。而对于PD-L1阴性或低表达这类免疫治疗非优势人群,以PD-1单抗为基础的用药方案疗效有限,尝试双特异性抗体、ADC等不同药物的联合也是一种趋势。为了精准指导临床实践,中国抗癌协会胃癌专业委员会组织国内胃癌领域专家进行多轮讨论,系统汇总国内外最新指南和循证证据,并结合我国临床实际,从病理检测、晚期治疗以及围术期治疗三个方面制定了本专家共识,旨在提高胃癌诊治的科学性和规范性,尤其是指导基层医生对免疫治疗的选择和应用。

     

  • 表  1  循证医学证据等级及定义

    证据等级定义
    I级(高质量)进一步研究几乎不可能改变对临床疗效评估结果的可信度,为高级别证据
    II级(中等质量)进一步研究可能改变对疗效评估结果的可信度有重要影响,为中级别证据
    III级(低质量)进一步研究很可能改变对疗效评估结果的可信度有重要影响,且极有可能改变评估结果,为低级别证据
    IV级(极低质量)任何疗效评估结果都不确定,为低级别证据
    下载: 导出CSV

    表  2  晚期胃癌一线免疫治疗研究概览

    晚期一线研究 研究方案 主要终点 人群 n 人群占比(%) OS(月) PFS(月) ORR(%) DoR
    CheckMate-649 纳武利尤单抗+FOLFOX/XELOX PFS和OS CPS≥5 955 60.4 14.1 vs.11.1 8.3 vs. 6.1 60 vs. 45 9.6 vs. 7.0
    (HR=0.70) (HR=0.70)
    ITT 1581 100 13.7 vs. 11.6 7.7 vs. 6.9 58 vs. 46 8.5 vs. 6.9
    (HR=0.79) (HR=0.79)
    KEYNOTE-859 帕博利珠单抗+XELOX/FP OS CPS≥10 551 34.9 15.7 vs.11.8 8.1 vs. 5.6 60.6 vs. 43.0 10.9 vs. 5.8
    (HR=0.65) (HR=0.62)
    CPS≥1 1235 78.2 13.0 vs. 11.4 6.9 vs. 5.6 52.1 vs. 42.6 8.3 vs.5.6
    (HR=0.74) (HR=0.72)
    ITT 1579 100 12.9 vs. 11.5 6.9 vs. 5.6 51.3 vs. 41.2 8.0 vs.5.7
    (HR=0.78) (HR=0.76)
    ORIENT-16 信迪利单抗+XELOX OS CPS≥5 397 61.1 18.4 vs. 12.9 7.7 vs. 5.8 63.6 vs. 49.4 9.8 vs.7.1
    (HR=0.66) (HR=0.63)
    ITT 650 100 15.2 vs.12.3 7.1 vs.5.7 58.2 vs. 48.8 9.8 vs. 7.0
    (HR=0.77) (HR=0.64)
    RATIONALE-305 替雷利珠单抗+XELOX或FP OS TAP≥5% 546 54.8 16.4 vs.12.8 7.2 vs.5.9 50.4 vs. 43.0 9.0 vs. 7.1
    (HR=0.71) (HR=0.67)
    ITT 997 100 15.0 vs. 12.9 6.9 vs. 6.2 47.3 vs. 40.5 8.6 vs. 7.2
    (HR=0.80) (HR=0.78)
    GEMSTONE-303 舒格利单抗+CAPOX PFS和OS CPS≥10 258 53.9 17.81 vs. 12.45 7.79 vs. 5.52 - -
    (HR=0.64) (HR=0.58)
    CPS≥5 479 100 15.64 vs. 12.65 7.62 vs. 6.08 68.6 vs. 52.7 6.87 vs. 4.63
    (HR=0.75) (HR=0.66)
    AK104-201 卡度尼利单抗+mXELOX ORR和安全性 CPS<1 50 53.2 17.64 8.18 - -
    CPS≥1 42 44.7 17.48 9.2 - -
    CPS<5 78 83 17.28 7.23 - -
    CPS≥5 14 14.9 20.24 NR - -
    ITT 94 100 17.41 9.2 68.20% 9.69
    下载: 导出CSV

    表  3  毒性分级及治疗

    CTCAE分级 住院推荐 糖皮质激素的使用推荐 其他ICIs使用推荐 免疫治疗及后续应用
    G1 无须住院 不推荐使用 不推荐 继续使用
    G2
    无须住院 局部或全身治疗,口服泼尼松或甲泼
    尼龙0.5~1.0 mg/(kg·d)
    不推荐 暂停使用*
    G3 住院治疗 全身治疗,口服或使用泼尼松或甲泼
    尼龙1~2 mg/(kg·d)
    激素治疗2~5 d后症状未能缓
    解的患者,可考虑在专科医师指导下使用
    停用,基于患者的风险-获益比讨论是否恢复免疫治疗
    G4 住院治疗,考虑收入重症加强护理病房(ICU)治疗 全身糖皮质激素治疗,静脉使用甲泼
    尼龙1~2 mg/(kg·d),连续3 d,
    症状缓解逐渐减量至1 mg/(kg·d)维持,
    后逐步减量,4-6周停药
    对糖皮质激素治疗2-5天后症状未能缓解的患者,可考虑在专科医师指导下使用 永久停用
    CTCAE:常见不良事件评价标准(Common Terminology Criteria for Adverse Events);ICU:重症监护病房(intensive care unit);*:如仅表现为皮肤或内分泌症状,免疫治疗可继续。
    下载: 导出CSV
  • [1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249. doi: 10.3322/caac.21660
    [2] Wang H, Guo WH, Hu YF, et al. Superiority of the 8th edition of the TNM staging system for predicting overall survival in gastric cancer: comparative analysis of the 7th and 8th editions in a monoinstitutional cohort[J]. Mol Clin Oncol, 2018, 9(4):423-431.
    [3] Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer[J]. Lancet, 2020, 396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5
    [4] Catenacci DVT, Moya S, Lomnicki S, et al. Personalized antibodies for gastroesophageal adenocarcinoma (PANGEA): a phase II study evaluating an individualized treatment strategy for metastatic disease[J]. Cancer Discov, 2021, 11(2):308-325. doi: 10.1158/2159-8290.CD-20-1408
    [5] Zeng HM, Chen WQ, Zheng RS, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health, 2018, 6(5):e555-e567. doi: 10.1016/S2214-109X(18)30127-X
    [6] Boku N, Satoh T, Ryu MH, et al. Nivolumab in previously treated advanced gastric cancer (ATTRACTION-2):3-year update and outcome of treatment beyond progression with nivolumab[J]. Gastric Cancer, 2021, 24(4):946-958. doi: 10.1007/s10120-021-01173-w
    [7] Janjigian YY, 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. doi: 10.1016/S0140-6736(21)00797-2
    [8] Shitara K, van Cutsem E, Bang YJ, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: the KEYNOTE-062 phase 3 randomized clinical trial[J]. JAMA Oncol, 2020, 6(10):1571-1580. doi: 10.1001/jamaoncol.2020.3370
    [9] Janjigian YY, Kawazoe A, Yañez P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer[J]. Nature, 2021, 600(7890):727-730. doi: 10.1038/s41586-021-04161-3
    [10] Xu JM, Jiang HP, Pan YY, et al. Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer: the ORIENT-16 randomized clinical trial[J]. JAMA, 2023, 330(21):2064-2074. doi: 10.1001/jama.2023.19918
    [11] Zhang L, Wang YK, Li ZW, et al. Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer[J]. Diagn Pathol, 2021, 16(1):38. doi: 10.1186/s13000-021-01099-y
    [12] Böger C, Behrens HM, Mathiak M, et al. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients[J]. Oncotarget, 2016, 7(17):24269-24283. doi: 10.18632/oncotarget.8169
    [13] Wainberg ZA, Fuchs CS, Tabernero J, et al. Efficacy of pembrolizumab monotherapy for advanced gastric/gastroesophageal junction cancer with programmed death ligand 1 combined positive score ≥10[J]. Clin Cancer Res, 2021, 27(7):1923-1931. doi: 10.1158/1078-0432.CCR-20-2980
    [14] Henriksen TV, Tarazona N, Frydendahl A, et al. Circulating tumor DNA in stage III colorectal cancer, beyond minimal residual disease detection, toward assessment of adjuvant therapy efficacy and clinical behavior of recurrences[J]. Clin Cancer Res, 2022, 28(3):507-517. doi: 10.1158/1078-0432.CCR-21-2404
    [15] 中国抗癌协会肿瘤病理专业委员会,中国临床肿瘤学会肿瘤病理专家委员会,中国临床肿瘤学会非小细胞肺癌专家委员会.中国非小细胞肺癌PD-L1表达检测临床病理专家共识[J].中华肿瘤杂志,2020,42(7):513-521.
    [16] 薛丽燕,李印,黄镜.中国食管癌PD-L1蛋白表达检测临床病理专家共识[J].中华肿瘤杂志,2023,45(4):291-297.
    [17] Moehler MH, Kato K, Arkenau HT, et al. Rationale 305: phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1L) of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC)[J]. J Clin Oncol, 2023, 41(suppl_4):286.
    [18] Kulangara K, Zhang N, Corigliano E, et al. Clinical utility of the combined positive score for programmed death ligand-1 expression and the approval of pembrolizumab for treatment of gastric cancer[J]. Arch Pathol Lab Med, 2019, 143(3):330-337. doi: 10.5858/arpa.2018-0043-OA
    [19] Yeong J, Lum HYJ, Teo CB, et al. Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy[J]. Gastric Cancer, 2022, 25(4):741-750. doi: 10.1007/s10120-022-01301-0
    [20] Janjigian YY, Ajani JA, Moehler M, et al. LBA7 Nivolumab (NIVO) plus chemotherapy (Chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): checkmate 649 study[J]. Ann Oncol, 2021, 32(suppl_5):S1329-S1330.
    [21] Rha SY, Wyrwicz LS, Weber PEY, et al. VP1-2023: Pembrolizumab (pembro) plus chemotherapy (chemo) as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) cancer: phase III KEYNOTE-859 study[J]. Ann Oncol, 2023, 34(3):319-320. doi: 10.1016/j.annonc.2023.01.006
    [22] Zhang X, Wang J, Wang G, et al. LBA79 GEMSTONE-303: Prespecified progression-free survival (PFS) and overall survival (OS) final analyses of a phase III study of sugemalimab plus chemotherapy vs placebo plus chemotherapy in treatment-naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma[J]. Ann Oncol, 2023, 34(Suppl_2):S1319.[LinkOut
    [23] Ji JF, Shen L, Gao XY, et al. A phase Ib/II, multicenter, open-label study of AK104, a PD-1/CTLA-4 bispecific antibody, combined with chemotherapy (chemo) as first-line therapy for advanced gastric (G) or gastroesophageal junction (GEJ) cancer[J]. J Clin Oncol, 2022, 40(suppl_4):308.
    [24] Ji JF, Shen L, Li ZY, et al. A phase Ib/II, multicenter, open-label study of AK104, a PD-1/CTLA-4 bispecific antibody, combined with chemotherapy (chemo) as first-line therapy for advanced gastric (G) or gastroesophageal junction (GEJ) cancer: 2-Year update data[J]. J Clin Oncol, 2023, 41(suppl_16):4031.
    [25] Shen L, Li J, Deng YH, et al. Envafolimab (KN035) in advanced tumors with mismatch-repair deficiency[J]. J Clin Oncol, 2020, 38(suppl_15):3021.
    [26] Li J, Xu Y, Zang AM, et al. A phase 2 study of tislelizumab monotherapy in patients with previously treated, locally advanced unresectable ormetastatic microsatellite instability-high/mismatch repair deficient solid tumors[J]. J Clin Oncol, 2021, 39(suppl_15):2569.
    [27] Lorenzen S, Goetze TO, Hofheinz RD, et al. FLOT plus nivolumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: results from the randomized phase 2 IKF-S628/AIO-STO-0417 (Moonlight) trial of the AIO[J]. J Clin Oncol, 2023, 41(suppl_16):4045.
    [28] Fukuoka S, Hara H, Takahashi N, et al. Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: an open-label, dose-escalation, and dose-expansion phase ib trial (REGONIVO, EPOC1603)[J]. J Clin Oncol, 2020, 38(18):2053-2061. doi: 10.1200/JCO.19.03296
    [29] Herbst RS, Garon EB, Kim DW, et al. Long-term outcomes and retreatment among patients with previously treated, programmed death-ligand 1‒positive, advanced non‒small-cell lung cancer in the KEYNOTE-010 study[J]. J Clin Oncol, 2020, 38(14):1580-1590. doi: 10.1200/JCO.19.02446
    [30] Pires da Silva I, Ahmed T, Reijers ILM, et al. Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study[J]. Lancet Oncol, 2021, 22(6):836-847. doi: 10.1016/S1470-2045(21)00097-8
    [31] Betof Warner A, Palmer JS, Shoushtari AN, et al. Long-term outcomes and responses to retreatment in patients with melanoma treated with PD-1 blockade[J]. J Clin Oncol, 2020, 38(15):1655-1663. doi: 10.1200/JCO.19.01464
    [32] Xu ST, Shukuya T, Tamura J, et al. Heterogeneous outcomes of immune checkpoint inhibitor rechallenge in patients with NSCLC: a systematic review and meta-analysis[J]. JTO Clin Res Rep, 2022, 3(4):100309.
    [33] Terashima M, Kang YK, Kim YW, et al. ATTRACTION-5: a phase 3 study of nivolumab plus chemotherapy as postoperative adjuvant treatment for pathological stage III (pStage III) gastric or gastroesophageal junction (G/GEJ) cancer[J]. J Clin Oncol, 2023, 41(suppl_16):4000.
    [34] Bang YJ, van Cutsem E, Fuchs CS, et al. KEYNOTE-585: phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer[J]. Future Oncol, 2019, 15(9):943-952. doi: 10.2217/fon-2018-0581
    [35] André T, Tougeron D, Piessen G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma: the GERCOR NEONIPIGA phase II study[J]. J Clin Oncol, 2023, 41(2):255-265. doi: 10.1200/JCO.22.00686
    [36] Al-Batran SE, Lorenzen S, Thuss-Patience PC, et al. Surgical and pathological outcome, and pathological regression, in patients receiving perioperative atezolizumab in combination with FLOT chemotherapy versus FLOT alone for resectable esophagogastric adenocarcinoma: interim results from DANTE, a randomized, multicenter, phase IIb trial of the FLOT-AIO German Gastric Cancer Group and Swiss SAKK[J]. J Clin Oncol, 2022, 40(suppl_16):4003.
    [37] 中国临床肿瘤学会. 免疫检查点抑制剂相关的毒性管理指南.2023[M].第一版.北京:人民卫生出版社, 2023:1-192.
  • 加载中
表(3)
计量
  • 文章访问数:  971
  • HTML全文浏览量:  54
  • PDF下载量:  324
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-12-28
  • 录用日期:  2024-01-24
  • 修回日期:  2024-01-24
  • 网络出版日期:  2024-01-25

目录

    /

    返回文章
    返回