Department of Oncology Asan Medical Centre, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea.
Nanjing Tianyinshan Hospital, The First Affiliated Hospital of China Pharmaceutical University, Nanjing, China.
Gastric Cancer. 2024 Sep;27(5):1046-1057. doi: 10.1007/s10120-024-01516-3. Epub 2024 Jun 11.
BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.
背景:在 FIGHT 研究(NCT03694522)中,贝伐珠单抗,一种针对成纤维细胞生长因子受体 2b(FGFR2b)的人源化单克隆抗体,联合 mFOLFOX6 方案在 FGFR2b 阳性(免疫组织化学检测 2+/3+膜染色)局部晚期不可切除/转移性胃/胃食管交界处癌(G/GEJC)患者中显示出具有临床意义的疗效。FIGHT 研究中的很大一部分患者在东亚入组,反映了 G/GEJC 的全球流行病学。
方法:这项 FIGHT 全球、2 期、双盲研究的亚组分析纳入了所有在东亚研究地点入组的患者。患者按 1:1 随机分配接受贝伐珠单抗-mFOLFOX6(第 1 周期 15mg/kg 和第 8 天 1 次 7.5mg/kg 剂量)或匹配的安慰剂-mFOLFOX6。主要终点是研究者评估的无进展生存期(PFS)。次要终点包括总生存期(OS)、客观缓解率和安全性。在至少 24 个月的随访后评估疗效。
结果:东亚亚组包括 89 例患者(占总研究人群的 57%);45 例患者被随机分配接受贝伐珠单抗-mFOLFOX6 治疗,44 例患者接受安慰剂-mFOLFOX6 治疗。贝伐珠单抗-mFOLFOX6 组的中位 PFS(95%置信区间[CI])为 12.9 个月(8.8-17.9),安慰剂-mFOLFOX6 组为 8.2 个月(5.6-10.3)(HR 0.50,95%CI 0.29-0.87);中位 OS(95%CI)分别为 24.7 个月(13.8-33.1)和 12.9 个月(9.3-21.4)(HR 0.56,95%CI 0.32-0.96)。在肿瘤细胞中 FGFR2b 阳性率≥10%的患者中,贝伐珠单抗-mFOLFOX6 治疗的获益更为显著。未报告新的安全性信号。
结论:在全球 FIGHT 研究中入组的 FGFR2b 阳性晚期/转移性 G/GEJC 的东亚患者中,贝伐珠单抗-mFOLFOX6 方案与安慰剂-mFOLFOX6 相比,具有显著的临床获益。
Cancer Chemother Pharmacol. 2020-11
Cancer Commun (Lond). 2025-3
Cancers (Basel). 2023-5-6
Gastric Cancer. 2023-1