Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Gusu School, Nanjing medical University, Suzhou, China.
Signal Transduct Target Ther. 2024 Mar 25;9(1):73. doi: 10.1038/s41392-024-01773-9.
Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).
患者患有晚期胃癌，通常预后较差。这项 1a 期（剂量递增）和 1b 期（剂量扩展）研究调查了一线卡瑞利珠单抗联合阿帕替尼和化疗治疗晚期胃或胃食管交界处腺癌的安全性和有效性。主要终点包括 1a 期的最大耐受剂量（MTD）和 1a 期和 1b 期的客观缓解率（ORR）。1a 期测试了卡瑞利珠单抗、阿帕替尼、奥沙利铂和 S-1 的三种剂量方案。方案 1：卡瑞利珠单抗 200mg，第 1 天；阿帕替尼 250mg，每两天一次；奥沙利铂 100mg/m²，第 1 天；S-1 40mg，每天两次，第 1-14 天。方案 2：与方案 1 相同，但奥沙利铂 130mg/m²。方案 3：与方案 2 相同，但阿帕替尼每天 250mg。34 名患者入组（1a 期 9 名，1b 期 25 名）。未发生剂量限制毒性，因此未确定 MTD。方案 3被设定为推荐的 2 期剂量，并在 1b 期进行。确认的 ORR 为 76.5%（95%CI 58.8-89.3）。中位无进展生存期为 8.4 个月（95%CI 5.9-NE），中位总生存期（OS）尚未成熟（11.6-NE）。10 名患者在治疗后接受了手术，由多学科团队进行评估。在 24 名未手术的患者中，中位 OS 为 19.6 个月（7.8-NE）。18 名患者（52.9%）发生≥3 级治疗相关不良事件。卡瑞利珠单抗联合阿帕替尼和化疗为未经治疗的晚期胃癌患者带来了良好的临床获益和可管理的安全性（ChiCTR2000034109）。
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