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
The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Internal Medicine, AMITA Health Saint Joseph Hospital Chicago, Chicago, Illinois, United States.
Front Oncol. 2022 Aug 26;12:927781. doi: 10.3389/fonc.2022.927781. eCollection 2022.
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/m, IV, d1 with capecitabine 1,000 mg/m, 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% ( 0.246), whereas the MPR rate was 78.9% vs. 36.4% ( 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. : Chictr.org.cn, identifier ChiCTR2000030414.
新辅助化疗已被广泛推荐用于局部晚期胃癌（LAGC）患者。然而，缺乏新辅助化疗联合抗程序性死亡1（anti-PD-1）抗体治疗LAGC患者的证据。因此，我们开展了一项单臂II期试验，以评估抗PD-1抗体信迪利单抗联合XELOX方案（卡培他滨加奥沙利铂）治疗LAGC患者的疗效和安全性。
纳入LAGC患者（cT3-4 N+ M0，CY0，P0），接受4个周期术前信迪利单抗（200 mg，静脉注射，每21天1次）联合XELOX方案（奥沙利铂130 mg/m²，静脉注射，第1天；卡培他滨1000 mg/m²，每日2次，第1 - 14天，每21天1次）治疗。主要终点为病理完全缓解（pCR）率。本临床试验在Chictr.org.cn注册（试验编号：ChiCTR2000030414）。
2020年3月至2021年7月共纳入30例患者，中位年龄62岁（范围30 - 72岁），男性18例（60.0%）。19例（63.3%）患者的PD-L1综合阳性评分（CPS）≥1。pCR率为33.3%[95%置信区间（CI），17.3% - 52.8%]，主要病理缓解（MPR）率为63.3%（95% CI，43.9% - 80.1%）。所有患者均接受了R0切除。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%）。22例（73.3%）患者观察到总体TNM分期降期。PD-L1 CPS≥1患者和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）。潜在的免疫相关不良事件（irAE）为甲状腺功能减退（3.3%）、肺炎（10.0%）和皮炎（6.7%）。新辅助治疗期间3级常见治疗相关不良事件（TRAE）为谷丙转氨酶升高（3.3%）、谷草转氨酶升高（3.3%）和皮炎（3.3%）。无与手术相关的严重并发症或死亡。
信迪利单抗联合XELOX作为新辅助治疗显示出令人鼓舞的pCR率、MPR率且安全性可控。这种联合方案可能为LAGC患者提供一种新的选择。试验注册机构：Chictr.org.cn，标识符ChiCTR2000030414 。
