Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Immunother Cancer. 2022 Mar;10(3). doi: 10.1136/jitc-2021-003635.
Immune checkpoint inhibitors have greatly improved the prognoses of diverse advanced malignancies, including gastric and gastroesophageal junction (G/GEJ) cancer. However, the role of anti-programmed cell death protein-1 treatment in the neoadjuvant setting remains unclear. This phase 2 study aimed to evaluate sintilimab plus CapeOx as a neoadjuvant regimen in patients with advanced resectable G/GEJ adenocarcinoma. Eligible patients with resectable G/GEJ adenocarcinoma stage cT3-4NanyM0 were enrolled. Patients received neoadjuvant treatment with sintilimab (3 mg/kg for cases <60 kg or 200 mg for those ≥60 kg on day 1) plus CapeOx (oxaliplatin at 130 mg/m on D1 and capecitabine at 1000 mg/m two times per day on D1-D14) every 21 days, for three cycles before surgical resection, followed by adjuvant treatment with three cycles of CapeOx with the same dosages after surgical resection. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included objective response rate, tumor regression grade per Becker criteria, survival and safety. As of July 30, 2020, 36 patients were enrolled. Totally 7 (19.4%) patients had GEJ cancer, and 34 (94.4%) patients were clinical stage III cases. A total of 35 (97.2%) patients completed three cycles of neoadjuvant treatment, and 1 patients received two cycles due to adverse events. All patients underwent surgery and the R0 resection rate was 97.2%. In this study, pCR and major pathological response were achieved in 7 (19.4%, 95% CI: 8.8% to 35.7%; 90% CI: 10.7% to 33.1%) and 17 (47.2%, 95% CI: 31.6% to 64.3%) patients, respectively. Thirty-one patients received adjuvant treatment. By December 20, 2021, three patients died after disease relapse, and two patients were alive with relapse. Median disease-free survival (DFS) and overall survival (OS) were not reached. The 1-year DFS and OS rates were 90.3% (95% CI: 80.4% to 100.0%) and 94.1% (95% CI: 86.5% to 100.0%), respectively. The most common (>1 patient) grade 3 treatment-related adverse events during neoadjuvant treatment were anemia and neutropenia (n=5 each, 13.9%). No serious adverse events (AEs) or grade 4-5 AEs were observed. Sintilimab plus oxaliplatin/capecitabine showed promising efficacy with encouraging pCR rate and good safety profile in the neoadjuvant setting. This combination regimen might present a new option for patients with locally advanced, resectable G/GEJ adenocarcinoma. Trial registration; NCT04065282.
免疫检查点抑制剂极大地改善了多种晚期恶性肿瘤的预后，包括胃癌和胃食管结合部（G/GEJ）癌。然而，抗程序性细胞死亡蛋白-1 治疗在新辅助治疗中的作用仍不清楚。本研究旨在评估信迪利单抗联合 CapeOx 在可切除的 G/GEJ 腺癌患者中的新辅助治疗作用。
符合要求的可切除 G/GEJ 腺癌 cT3-4NanyM0 患者纳入研究。患者接受信迪利单抗（体重<60kg 患者 3mg/kg，体重≥60kg 患者 200mg，第 1 天）联合 CapeOx（奥沙利铂 130mg/m2，第 1 天，卡培他滨 1000mg/m2，每日 2 次，第 1-14 天）新辅助治疗，每 21 天 1 个周期，共 3 个周期，手术前进行，术后接受 CapeOx 辅助治疗（剂量同前），共 3 个周期。主要终点为病理完全缓解（pCR）率。次要终点包括客观缓解率、Becker 标准肿瘤退缩分级、生存和安全性。截至 2020 年 7 月 30 日，共纳入 36 例患者。7 例（19.4%）患者为 GEJ 癌，34 例（94.4%）为临床 III 期。共 35 例（97.2%）患者完成 3 个周期新辅助治疗，1 例患者因不良反应接受 2 个周期。所有患者均接受手术，R0 切除率为 97.2%。在这项研究中，7 例（19.4%，95%CI：8.8%至 35.7%；90%CI：10.7%至 33.1%）和 17 例（47.2%，95%CI：31.6%至 64.3%）患者达到了 pCR 和主要病理缓解。31 例患者接受了辅助治疗。截至 2021 年 12 月 20 日，3 例患者疾病复发后死亡，2 例患者仍在复发中存活。中位无疾病生存期（DFS）和总生存期（OS）均未达到。1 年 DFS 和 OS 率分别为 90.3%（95%CI：80.4%至 100.0%）和 94.1%（95%CI：86.5%至 100.0%）。新辅助治疗期间最常见（≥1 例患者）的 3 级治疗相关不良事件为贫血和中性粒细胞减少（各 5 例，13.9%）。未观察到严重不良事件（AE）或 4-5 级 AE。信迪利单抗联合奥沙利铂/卡培他滨在新辅助治疗中具有良好的疗效和安全性，pCR 率较高。该联合方案可能为局部晚期可切除 G/GEJ 腺癌患者提供新的治疗选择。
NCT04065282。
