中山大学肿瘤防治中心徐瑞华教授团队研究了替雷利珠单抗加化疗治疗晚期胃或胃食管交界腺癌的疗效与安全性。相关论文于2024年5月28日发表在《英国医学杂志》上。

为了与安慰剂加化疗相比，评估替雷利珠单抗作为晚期胃或胃食管交界腺癌一线（主要）治疗的疗效和安全性，2018年12月13日至2023年2月28日，研究组在亚洲、欧洲和北美的146个医疗中心进行了一项随机、双盲、安慰剂对照的3期临床研究。共招募了1657名年龄≥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交界腺癌患者，无论程序性死亡配体1（PD-L1）表达状态如何，他们均未接受过晚期疾病的系统抗癌治疗。

这些患者被随机（1:1）分配为每三周静脉注射一次200 mg替雷利珠单抗或安慰剂，并联合化疗（研究者选择奥沙利铂和卡培他滨，或顺铂和5-氟尿嘧啶），并按病灶区域、PD-L1表达、腹膜转移的存在与否以及研究者选择的化疗进行分层。治疗持续到疾病进展或出现不可接受的毒性。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。对所有接受至少一剂研究治疗的患者进行了安全性评估。

在2018年12月13日至2021年2月9日期间筛查的1657名患者中，660人因不符合资格标准、撤回同意书、不良事件或其他原因而不符合资格。总体而言，997人被随机分配接受替雷利珠单抗加化疗（n=501）或安慰剂加化疗（n=496）。在PD-L1 TAP评分≥5%的患者中，替雷利珠单抗联合化疗与安慰剂联合化疗相比，总体生存率有统计学意义的改善（中位数17.2个月vs12.6个月；危险比0.74（95%置信区间0.59至0.94）；P=0.006（中期分析）），在所有随机患者中两组结果相似（中位数15.0个月比12.9个月；危险比0.80（0.70-0.92）；P=0.001（最终分析））。替雷利珠单抗加化疗组中54%（268/498）的患者观察到3级或更糟的治疗相关不良事件，而安慰剂加化疗组为50%（246/494）。

研究结果表明，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，替雷利珠单抗加化疗作为晚期或转移性胃或胃食管交界腺癌的主要治疗，提供了更高的总生存率和可控的安全性。

附：英文原文

Title: Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial

Author: Miao-Zhen Qiu, Do-Youn Oh, Ken Kato, Tobias Arkenau, Josep Tabernero, Marcia Cruz Correa, Anastasia V Zimina, Yuxian Bai, Jianhua Shi, Keun-Wook Lee, Jufeng Wang, Elena Poddubskaya, Hongming Pan, Sun Young Rha, Ruixing Zhang, Hidekazu Hirano, David Spigel, Kensei Yamaguchi, Yee Chao, Lucjan Wyrwicz, Umut Disel, Roberto Pazo Cid, Lorenzo Fornaro, Ludovic Evesque, Hongwei Wang, Yaling Xu, Jiang Li, Tao Sheng, Silu Yang, Liyun Li, Markus Moehler, Rui-Hua Xu

Issue&Volume: 2024/05/28

Abstract:

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.

DOI: 10.1136/bmj-2023-078876

Source: https://www.bmj.com/content/385/bmj-2023-078876