Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China.
J Clin Pharmacol. 2023 Jul;63(7):769-775. doi: 10.1002/jcph.2237. Epub 2023 May 5.
Combining immune checkpoint inhibitors with vascular endothelial growth factor/vascular endothelial growth factor receptor inhibitors is effective in treating a number of solid tumors; however, evidence in advanced gastric/gastroesophageal junction (G/GEJ) cancer is limited. This retrospective study included consecutive patients who received a programmed cell death protein 1 (PD-1) inhibitor plus the vascular endothelial growth factor receptor 2 inhibitor apatinib, second-line or later to treat unresectable advanced or metastatic, histologically proven, human epidermal growth factor receptor 2-negative G/GEJ cancer in a single center between November 1, 2018, and March 31, 2021. Treatment was continued until the disease progressed or the toxicity became intolerable. We examined data from 52 patients. The primary tumor site was the stomach in 29 patients and the GEJ in 23 patients. PD-1 inhibitors administered included camrelizumab (n = 28), sintilimab (n = 18), pembrolizumab (n = 3), and tislelizumab (n = 1), and all patients were given 200 mg every 3 weeks, and toripalimab (240 mg every 3 weeks) and nivolumab (200 mg every 2 weeks) were given to 1 patient each. For 28 days, apatinib 250 mg was administered orally once a day. The objective response rate was 15.4% (95% confidence interval [CI], 6.9-28.1), and the disease control rate was 61.5% (95%CI, 47.0-74.7). After 14.8 months of median follow-up, the median progression-free survival was 4.2 months (95%CI, 2.6-4.8), and the overall survival was 9.3 months (95%CI, 7.9-12.9). Twelve patients underwent grade 3-4 treatment-related adverse events (23.1%). There was no unexpected toxicity or death. This trial demonstrated combination therapy with an anti-PD-1 antibody and apatinib was effective and safe in patients with previously treated unresectable advanced or metastatic G/GEJ cancer.
联合免疫检查点抑制剂和血管内皮生长因子/血管内皮生长因子受体抑制剂在治疗多种实体瘤方面有效;然而,晚期胃/胃食管交界处(G/GEJ)癌症的证据有限。这项回顾性研究纳入了 2018 年 11 月 1 日至 2021 年 3 月 31 日期间在一家中心接受程序性死亡蛋白 1(PD-1)抑制剂联合血管内皮生长因子受体 2 抑制剂阿帕替尼二线或后线治疗不可切除的晚期或转移性、组织学证实的人表皮生长因子受体 2 阴性 G/GEJ 癌症的连续患者。治疗持续到疾病进展或毒性无法耐受为止。我们检查了 52 例患者的数据。原发性肿瘤部位为胃 29 例,GEJ 23 例。给予的 PD-1 抑制剂包括卡瑞利珠单抗(n=28)、替雷利珠单抗(n=18)、帕博利珠单抗(n=3)和替西利珠单抗(n=1),所有患者均每 3 周给予 200mg,1 例患者给予特瑞普利单抗(240mg 每 3 周)和纳武利尤单抗(200mg 每 2 周)。阿帕替尼 250mg 每天口服一次,连续 28 天。客观缓解率为 15.4%(95%置信区间[CI],6.9-28.1),疾病控制率为 61.5%(95%CI,47.0-74.7)。中位随访 14.8 个月后,中位无进展生存期为 4.2 个月(95%CI,2.6-4.8),总生存期为 9.3 个月(95%CI,7.9-12.9)。12 例患者发生 3-4 级治疗相关不良事件(23.1%)。无意外毒性或死亡。这项试验表明,在先前治疗的不可切除的晚期或转移性 G/GEJ 癌症患者中,抗 PD-1 抗体联合阿帕替尼治疗是有效和安全的。