本文由小咖机器人翻译整理

期刊来源：BMJ

原文链接：https://doi.org/10.1136/bmj-2023-078876

摘要内容如下：

客观

与安慰剂加化疗相比，评估tislelizumab联合化疗作为一线（主要）治疗晚期胃或胃食管连接部腺癌的疗效和安全性。

设计

随机，双盲，安慰剂对照，3期研究。

设置

2018年12月13日至2023年2月28日期间，亚洲、欧洲和北美的146家医疗中心。

参与者

1657例年龄≥18岁的人表皮生长因子受体2阴性的局部晚期不可切除或转移性胃或胃食管连接部腺癌患者，无论程序性死亡配体1（PD-L1）表达状态如何，均未接受晚期疾病的全身抗癌治疗。

干预措施

患者被随机（1:1）分配接受tislelizumab 200 mg或安慰剂每三周静脉注射，联合化疗（研究者选择奥沙利铂和卡培他滨，或顺铂和5-氟尿嘧啶），并根据区域、PD-L1表达、是否存在腹膜转移以及研究者选择的化疗进行分层。治疗持续到疾病进展或不可接受的毒性。

主要结果指标

主要终点是PD-L1肿瘤区域阳性（TAP）评分≥5%的患者和所有随机患者的总生存率。在所有接受至少一剂研究治疗的患者中进行安全性评估。

结果

在2018年12月13日至2021年2月9日期间筛查的1657名患者中，有660名患者因不符合资格标准、撤回同意书、不良事件或其他原因而不合格。总体而言，997名患者被随机分配接受tislelizumab联合化疗（n=501）或安慰剂联合化疗（n=496）。在PD-L1 TAP评分≥5%的患者中，Tislelizumab联合化疗与安慰剂联合化疗相比，总生存率的改善具有统计学意义（中位数17.2个月vs 12.6个月；危害比0.74（95%置信区间0.59至0.94）；P=0.006（中期分析））和所有随机患者（中位数15.0个月对12.9个月；风险比为0.80（0.70至0.92）；P=0.001（最终分析））。在tislelizumab联合化疗组中，54%（268/498）的患者出现了3级或更严重的治疗相关不良事件，而在安慰剂联合化疗组中，这一比例为50%（246/494）。

结论

在PD-L1 TAP评分≥5%的患者和所有随机患者中，与安慰剂加化疗相比，Tislelizumab联合化疗作为晚期或转移性胃癌或胃食管连接部腺癌的主要治疗方案，提供了更高的总生存率和可控的安全性。

试用注册

ClinicalTrials.gov NCT03777657。

英文原文如下：

Abstracts

OBJECTIVE  To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy.

DESIGN  Randomised, double blind, placebo controlled, phase 3 study.

SETTING  146 medical centres across Asia, Europe, and North America, between 13 December 2018 and 28 February 2023.

PARTICIPANTS  1657 patients aged ≥18 years with human epidermal growth factor receptor 2 negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease.

INTERVENTIONS  Patients were randomly (1:1) assigned to receive either tislelizumab 200 mg or placebo intravenously every three weeks in combination with chemotherapy (investigator's choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator's choice of chemotherapy. Treatment continued until disease progression or unacceptable toxicity.

MAIN OUTCOME MEASURES  The primary endpoint was overall survival, both in patients with a PD-L1 tumour area positivity (TAP) score of ≥5% and in all randomised patients. Safety was assessed in all those who received at least one dose of study treatment.

RESULTS  Of 1657 patients screened between 13 December 2018 and 9 February 2021, 660 were ineligible due to not meeting the eligibility criteria, withdrawal of consent, adverse events, or other reasons. Overall, 997 were randomly assigned to receive tislelizumab plus chemotherapy (n=501) or placebo plus chemotherapy (n=496). Tislelizumab plus chemotherapy showed statistically significant improvements in overall survival versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5% (median 17.2 months v 12.6 months; hazard ratio 0.74 (95% confidence interval 0.59 to 0.94); P=0.006 (interim analysis)) and in all randomised patients (median 15.0 months v 12.9 months; hazard ratio 0.80 (0.70 to 0.92); P=0.001 (final analysis)). Grade 3 or worse treatment related adverse events were observed in 54% (268/498) of patients in the tislelizumab plus chemotherapy arm versus 50% (246/494) in the placebo plus chemotherapy arm.

CONCLUSIONS  Tislelizumab added to chemotherapy as primary treatment for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5%, and in all randomised patients.

TRIAL REGISTRATION  ClinicalTrials.gov NCT03777657.

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