Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Oncology, Cancer Center of Jinling Hospital, Nanjing University of Chinese Medicine, No. 34 Biao, 34 Hao, Yanggongjing Road, Qinhuai District, Nanjing, 210002, Jiangsu Province, China.
BMC Med. 2023 May 5;21(1):173. doi: 10.1186/s12916-023-02841-7.
Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings.
Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method.
Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1).
The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment.
This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.
阿帕替尼是一种高度选择性的 VEGFR2 抑制剂，在 2 期和 3 期试验中作为晚期胃癌的三线及以后的治疗药物，与安慰剂相比显著提高了疗效。本项前瞻性、单臂、多中心的 IV 期 AHEAD 研究旨在验证阿帕替尼在至少接受过两种系统治疗的晚期或转移性胃或胃食管腺癌患者中的安全性和疗效。
至少接受过两种化疗线治疗后疾病进展的晚期胃癌患者接受口服阿帕替尼治疗，直至疾病进展、死亡或出现无法耐受的毒性。主要终点为安全性。次要终点包括客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。不良反应发生率进行汇总。采用 Kaplan-Meier 法估计中位 OS 和 PFS。计算 ORR、DCR、3 个月和 6 个月时的 OS 以及 3 个月和 6 个月时的 PFS，并根据 Clopper-Pearson 法估计其 95%CI。
2015 年 5 月至 2019 年 11 月期间，共纳入 2004 例患者，1999 例接受至少一剂阿帕替尼治疗的患者被纳入安全性分析。在安全性人群中，87.9%的患者发生与治疗相关的不良反应（TRAEs），最常见的 TRAE 为高血压（45.2%）、蛋白尿（26.5%）和白细胞计数下降（25.3%）。此外，51%的患者发生了≥3 级 TRAE。57 例（2.9%）患者发生致死性 TRAE。未报告新的安全性问题。在纳入意向治疗人群的 2004 例患者中，ORR 为 4.4%（95%CI，3.6-5.4%），DCR 为 35.8%（95%CI，33.7-38.0%）。中位 PFS 为 2.7 个月（95%CI 2.2-2.8），中位 OS 为 5.8 个月（95%CI 5.4-6.1）。
AHEAD 研究的结果证实，阿帕替尼作为三线及以后的治疗药物，在晚期胃癌患者中具有可接受且可管理的安全性和临床获益。
本研究在 ClinicalTrials.gov 注册，注册号为 NCT02426034。注册日期为 2015 年 4 月 24 日。
