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.
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.
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一线Nivolumab加化学疗法与化学疗法仅用于晚期胃，胃食管结和食管腺癌（Checkmate 649）：一项随机，开放标签，第3阶段试验。
DOI：
10.1016/s0140-6736(21)00797-2
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发表时间：
2021-07-03
期刊：
影响因子：
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通讯作者：
Ajani JA
中科院分区：
文献类型：
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作者：
Janjigian YY;Shitara K;Moehler M;Garrido M;Salman P;Shen L;Wyrwicz L;Yamaguchi K;Skoczylas T;Campos Bragagnoli A;Liu T;Schenker M;Yanez P;Tehfe M;Kowalyszyn R;Karamouzis MV;Bruges R;Zander T;Pazo-Cid R;Hitre E;Feeney K;Cleary JM;Poulart V;Cullen D;Lei M;Xiao H;Kondo K;Li M;Ajani JA
晚期/转移性人表皮生长因子受体2（HER 2）阴性胃/胃食管交界处（GEJ）腺癌的一线化疗导致中位总生存期（OS）<1年。3期CheckMate 649研究评价了胃/GEJ/食管腺癌中基于一线程序性死亡（PD）-1肿瘤的治疗;我们报告了nivolumab+化疗与化疗的初步结果。我们招募了既往未经治疗、不可切除、非HER 2阳性胃/GEJ/食管腺癌的成人患者，无论PD-配体（L）1表达如何。患者被随机分配至nivolumab（360 mg，每3周一次或240 mg，每2周一次）+化疗（XTRIX，每3周一次或FOLFOX，每2周一次），nivolumab + ipilimumab或化疗。在PD-L1合并阳性评分（CPS）≥5的患者中，nivolumab+化疗与化疗的主要终点为OS或盲态独立中心审查的无进展生存期（PFS）。在接受至少一剂指定治疗的所有患者中评估安全性。从2017年3月至2019年4月，我们同时将1581例患者随机分配至治疗组（nivolumab+化疗，789例;化疗，792例）。OS的中位随访时间为：nivolumab+化疗，13.1个月（IQR，6.7 - 19.1），化疗，11.1个月（5.8 - 16.1）。在PD-L1 CPS ≥5例患者中，与化疗相比，Nivolumab+化疗导致OS（风险比[HR] 0.71 [98.4% CI 0.59 - 0.86]; p<0.0001）和PFS（HR 0.68 [98% CI 0.56 - 0.81]; p<0.0001）显著改善（最短随访时间，12.1个月）。其他结果显示，PD-L 1 CPS ≥1和全随机化患者的OS显着改善，沿着PFS获益。在所有接受治疗的患者中，462例（59%，nivolumab+化疗）和341例（44%，化疗）患者发生了3-4级治疗相关不良事件。未发现新的安全性信号。纳武利尤单抗是首个在既往未接受过治疗的晚期胃/GEJ/食管腺癌患者中证明与化疗联合治疗相比具有上级OS、沿着PFS获益和可接受的安全性特征的PD-1抑制剂。Nivolumab加化疗是这些患者的潜在标准一线治疗。布里斯托迈尔斯施贵宝（普林斯顿，新泽西州，美国），与小野制药公司合作，Ltd. ClinicalTrials.gov编号，NCT 02872116。
First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma results in median overall survival (OS) <1 year. The phase 3 CheckMate 649 study evaluated first-line programmed death (PD)-1 inhibitor-based therapies in gastric/GEJ/oesophageal adenocarcinoma; we report first results for nivolumab-plus-chemotherapy versus chemotherapy. We enrolled adults with previously untreated, unresectable, non-HER2-positive gastric/GEJ/oesophageal adenocarcinoma, regardless of PD-ligand (L)1 expression. Patients were randomised to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks)-plus-chemotherapy (XELOX every 3 weeks or FOLFOX every 2 weeks), nivolumab-plus-ipilimumab, or chemotherapy. Primary endpoints for nivolumab-plus-chemotherapy versus chemotherapy were OS or progression-free survival (PFS) by blinded independent central review, in PD-L1 combined positive score (CPS) ≥5 patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. From March 2017 through April 2019, we concurrently randomised 1581 patients to treatment (nivolumab-plus-chemotherapy, 789; chemotherapy, 792). The median follow-up for OS was: nivolumab-plus-chemotherapy, 13·1 months (IQR, 6·7–19·1) and chemotherapy, 11·1 months (5·8–16·1). Nivolumab-plus-chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59–0·86]; p<0·0001) and PFS (HR 0·68 [98% CI 0·56–0·81]; p<0·0001) versus chemotherapy in PD-L1 CPS ≥5 patients (minimum follow-up, 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in PD-L1 CPS ≥1 and all-randomised patients. Among all-treated patients, 462 (59%, nivolumab-plus-chemotherapy) and 341 (44%, chemotherapy) patients had grade 3–4 treatment-related adverse events. No new safety signals were identified. Nivolumab is the first PD-1 inhibitor to demonstrate superior OS, along with PFS benefit, and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric/GEJ/oesophageal adenocarcinoma. Nivolumab-plus-chemotherapy represents a potential standard first-line treatment for these patients. Bristol Myers Squibb (Princeton, NJ, USA), in collaboration with Ono Pharmaceutical Co., Ltd. ClinicalTrials.gov number, NCT02872116.