Efficacy and safety of sintilimab plus XELOX as a neoadjuvant regimen in patients with locally advanced gastric cancer: A single-arm, open-label, phase II trial.
Efficacy and safety of sintilimab plus XELOX as a neoadjuvant regimen in patients with locally advanced gastric cancer: A single-arm, open-label, phase II trial.
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DOI：
10.3389/fonc.2022.927781
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发表时间：
2022
影响因子：
4.7
通讯作者：
Zhao, Qun
中科院分区：
文献类型：
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作者：
Guo, Honghai;Ding, Ping'an;Sun, Chenyu;Yang, Peigang;Tian, Yuan;Liu, Yang;Lowe, Scott;Bentley, Rachel;Li, Yaru;Zhang, Zhidong;Wang, Dong;Li, Yong;Zhao, Qun
新辅助化疗已被广泛推荐用于局部晚期胃癌（LAGC）患者。然而，缺乏新辅助化疗与抗程序性死亡1（抗PD-1）抗体治疗LAGC患者的证据。因此，我们进行了一项单组II期试验，以评估抗PD-1抗体sintiliumab加XALIX方案（卡培他滨加奥沙利铂）在LAGC患者中的疗效和安全性。入组LAGC患者（cT 3 -4 N+ M0，CY 0，P0），术前接受4个周期的sintiliumab（200 mg，IV，Q21 d）联合XALIX（奥沙利铂130 mg/m2，IV，d1+卡培他滨1,000 mg/m2，bid，d1-d14，Q21 d）治疗。主要终点为病理学完全缓解（pCR）率。该临床试验在Chictr.org.cn注册（试验编号：ChiCTR 2000030414）。2020年3月至2021年7月入组了30例患者，中位年龄为62岁（范围：30-72岁），其中18例（60. 0%）为男性。PD-L1 CPS ≥ 1者19例（63.3%），pCR率为33.3%（95%CI，17.3%~ 52.8%），主要病理缓解率（MPR）为63.3%（95%CI，43.9%~ 80.1%）。所有患者均行R 0切除术。客观缓解率（ORR）和疾病控制率（DCR）分别为70.0%（95% CI，50.6%-85.3%）和100%（95% CI，88.4%-100%）。在22例（73.3%）患者中观察到总体TNM分期下调。PD-L1 CPS ≥1和PD-L1 CPS <1患者的pCR率分别为42.1%和18.2%（P = 0.246），而MPR率分别为78.9%和36.4%（P = 0.047）。潜在免疫相关不良事件（irAE）为甲状腺功能减退（3.3%）、肺炎（10.0%）和皮炎（6.7%）。3级常见治疗相关不良事件（TRAE）为新辅助治疗期间ALT升高（3.3%）、AST升高（3.3%）和皮炎（3.3%）。无手术相关严重并发症或死亡。新替利单抗联合XALIX作为新辅助治疗显示出令人鼓舞的pCR率、MPR率和可管理的安全性。这种联合治疗方案可能为LAGC患者提供一种新的选择。 临床试验注册：，标识符ChiCTR 2000030414。
Neoadjuvant chemotherapies have been widely recommended in patients with locally advanced gastric cancer (LAGC). However, the evidence of combining neoadjuvant chemotherapy with anti–programmed death 1 (anti–PD-1) antibody therapy for patients with LAGC is lacking. Thus, we conducted a single-arm phase II trial to evaluate the efficacy and safety of the anti–PD-1 antibody sintilimab plus XELOX regimen (capecitabine plus oxaliplatin) in patients with LAGC. Patients with LAGC (cT3-4 N+ M0, CY0, P0) were enrolled and received four preoperative cycles of sintilimab (200 mg, IV, Q21d) plus XELOX (oxaliplatin 130 mg/m2, IV, d1 with capecitabine 1,000 mg/m2, bid, d1–d14, Q21d) therapy. The primary endpoint was the pathological complete response (pCR) rate. This clinical trial was registered at Chictr.org.cn (trial number: ChiCTR2000030414). Thirty patients were enrolled from March 2020 to July 2021, with a median age of 62 years (range, 30–72), and 18 (60.0%) were men. There were 19 (63.3%) patients with PD-L1 CPS ≥1.The pCR rate was 33.3% [95% confidence interval (CI), 17.3%–52.8%], and the major pathologic response (MPR) rate was 63.3% (95% CI, 43.9%–80.1%). All the patients underwent R0 resection. The objective response rate (ORR) and the disease control rate (DCR) were 70.0% (95% CI, 50.6%–85.3%) and 100% (95% CI, 88.4%–100%), respectively. Downstaging of the overall TNM stage was observed in 22 (73.3%) patients. The pCR rate in patients with PD-L1 CPS ≥1 and patients with PD-L1 CPS <1 was 42.1% vs. 18.2% (P = 0.246), whereas the MPR rate was 78.9% vs. 36.4% (P = 0.047). The potential immune-related adverse events (irAEs) were hypothyroidism (3.3%), pneumonia (10.0%), and dermatitis (6.7%). Grade3 common treatment-related adverse events (TRAEs) were ALT increase (3.3%), AST increase (3.3%), and dermatitis (3.3%) during the neoadjuvant therapy. There were no severe complications or death related to the surgery. Sintilimab plus XELOX as neoadjuvant therapy showed an encouraging pCR rate, MPR rate, and manageable safety. This combination of regimens might provide a new option for patients with LAGC. Clinical Trial Registration: , identifier ChiCTR2000030414.
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DOI：
10.1007/s10120-018-0809-y
发表时间：
2018-09
期刊：
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
影响因子：
--
作者：
Lu Z;Zhang X;Liu W;Liu T;Hu B;Li W;Fan Q;Xu J;Xu N;Bai Y;Pan Y;Xu Q;Bai W;Xia L;Gao Y;Wang W;Shu Y;Shen L
通讯作者：
Shen L
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
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
发表时间：
2021-07-03
期刊：
Lancet (London, England)
影响因子：
--
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
通讯作者：
Ajani JA
影响因子：
10.9
作者：
Jiang H;Yu X;Li N;Kong M;Ma Z;Zhou D;Wang W;Wang H;Wang H;He K;Li Z;Lu Y;Zhang J;Zhao K;Zhang Y;Xu N;Li Z;Liu Y;Wang Y;Wang Y;Teng L
通讯作者：
Teng L
影响因子：
168.9
作者：
Bang, Yung-Jue;Kim, Young-Woo;Noh, Sung Hoon
通讯作者：
Noh, Sung Hoon