Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.
Harbin Medical University Cancer Hospital, Harbin, China.
Clin Cancer Res. 2020 Sep 1;26(17):4542-4550. doi: 10.1158/1078-0432.CCR-19-3561. Epub 2020 Jun 19.
This phase II study (NCT03469557) assessed safety/tolerability and antitumor activity of first-line tislelizumab, a monoclonal antibody against programmed cell death-1, plus chemotherapy in patients with locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.
Patients with ESCC received tislelizumab [200 mg i.v. every 3 weeks (Q3W)] plus cisplatin (80 mg/m² i.v. Q3W for ≤6 cycles) and fluorouracil (800 mg/m²/day i.v., Days 1-5 Q3W for ≤6 cycles); patients with G/GEJ adenocarcinoma received tislelizumab (200 mg i.v. Q3W) plus oxaliplatin (130 mg/m² i.v. Q3W for up to six cycles) and oral capecitabine (1,000 mg/m² twice daily, Days 1-14 Q3W). The safety/tolerability profile of combination therapy was the primary endpoint; secondary endpoints included objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression-free survival per RECIST v1.1. Exploratory endpoints included overall survival and potential predictive biomarkers.
As of March 31, 2019, 30 patients ( = 15 per cohort) were enrolled. Most common adverse events considered related to tislelizumab and/or chemotherapy were anemia ( = 18), decreased appetite ( = 17), nausea ( = 16), and asthenia ( = 15). One patient experienced fatal hepatic dysfunction, confounded by progressive disease and underlying hepatitis, attributed to treatment by the investigator. Confirmed ORRs and DCRs were 46.7% and 80%, respectively, for both ESCC and G/GEJ adenocarcinoma. In ESCC, median DoR was 12.8 months (95% confidence interval, 3.5-12.8); DoR was not yet mature for the G/GEJ cohort.
Tislelizumab plus chemotherapy demonstrated durable responses with manageable tolerability in patients with advanced ESCC or G/GEJ adenocarcinoma.
这项 II 期研究（NCT03469557）评估了一线替雷利珠单抗（一种针对程序性死亡受体-1 的单克隆抗体）联合化疗在局部晚期/转移性食管鳞状细胞癌（ESCC）或胃/胃食管交界处（G/GEJ）腺癌患者中的安全性/耐受性和抗肿瘤活性。
ESCC 患者接受替雷利珠单抗[200 mg 静脉注射，每 3 周（Q3W）]联合顺铂（80 mg/m² 静脉注射，Q3W，最多 6 个周期）和氟尿嘧啶（800 mg/m²/天，静脉注射，Q3W，最多 6 个周期）；G/GEJ 腺癌患者接受替雷利珠单抗（200 mg 静脉注射，Q3W）联合奥沙利铂（130 mg/m² 静脉注射，最多 6 个周期）和卡培他滨（1000 mg/m² 口服，每天 2 次，Q3W，14 天）。联合治疗的安全性/耐受性是主要终点；次要终点包括客观缓解率（ORR）、缓解持续时间（DoR）、疾病控制率（DCR）和根据 RECIST v1.1 评估的无进展生存期。探索性终点包括总生存期和潜在的预测生物标志物。
截至 2019 年 3 月 31 日，共纳入 30 例患者（每组 15 例）。最常见的被认为与替雷利珠单抗和/或化疗相关的不良事件是贫血（18 例）、食欲下降（17 例）、恶心（16 例）和乏力（15 例）。1 例患者发生致命性肝功能障碍，与疾病进展和潜在肝炎相关，由研究者认为与治疗有关。ESCC 和 G/GEJ 腺癌的确认 ORR 和 DCR 分别为 46.7%和 80%。在 ESCC 中，中位 DoR 为 12.8 个月（95%置信区间，3.5-12.8）；G/GEJ 队列的 DoR 尚未成熟。
替雷利珠单抗联合化疗在晚期 ESCC 或 G/GEJ 腺癌患者中显示出持久的缓解，且耐受性良好。
