Department of Medical Oncology, Cancer Center of Bayi Hospital, Nanjing Chinese Medicine University, Nanjing, China.
Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Lancet Gastroenterol Hepatol. 2021 Jul;6(7):559-568. doi: 10.1016/S2468-1253(21)00109-6. Epub 2021 May 8.
Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma.
AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov, NCT02329860.
Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand-foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators.
Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile.
Jiangsu Hengrui Medicine.
血管内皮生长因子受体（VEGFR）抑制剂在晚期肝细胞癌中显示出抗肿瘤活性，但在乙型肝炎病毒感染高发人群中，对 VEGFR 抑制剂的研究较少。本研究旨在评估阿帕替尼在预处理的晚期肝细胞癌患者中的疗效和安全性。
AHELP 是一项在中国 31 家医院进行的随机、双盲、安慰剂对照、3 期临床试验，纳入了先前对至少一线系统化疗或靶向治疗耐药或不耐受的晚期肝细胞癌患者（年龄≥18 岁）。患者按 2:1 的比例随机分配接受阿帕替尼 750mg 或安慰剂每日口服，28 天为一个治疗周期。分组采用中央随机系统进行，设为 6 个区组，按东部合作肿瘤学组体能状态、索拉非尼治疗史以及血管侵犯或肝外转移的存在进行分层。主要终点是总生存期，定义为随机分组至任何原因死亡的时间，在随机分组并接受至少一剂研究药物的患者中进行分析。安全性分析在接受至少一剂研究治疗且有治疗后安全性评估的患者中进行。该试验在 ClinicalTrials.gov 注册，编号为 NCT02329860。
2014 年 4 月 1 日至 2017 年 5 月 3 日，400 名符合条件的患者被随机分配接受阿帕替尼（n=267）或安慰剂（n=133）治疗。7 名患者（阿帕替尼组 6 名，安慰剂组 1 名）未接受研究治疗，被排除在疗效分析之外。与安慰剂组相比，阿帕替尼组的总生存期显著延长（中位 8.7 个月[95%CI 7.5-9.8]比 6.8 个月[5.7-9.1]；风险比 0.785[95%CI 0.617-0.998]，p=0.048）。387 名（阿帕替尼组 257 名，安慰剂组 130 名）患者在接受研究治疗后进行了安全性评估，并纳入安全性分析。最常见的 3 级或 4 级与治疗相关的不良事件是高血压（阿帕替尼组 71[28%]例，安慰剂组 3[2%]例）、手足综合征（阿帕替尼组 46[18%]例，安慰剂组无）和血小板计数减少（阿帕替尼组 34[13%]例，安慰剂组 1[1%]例）。阿帕替尼组 24（9%）名患者和安慰剂组 13（10%）名患者因不良事件死亡，但研究人员认为这些死亡均与治疗无关。
与安慰剂相比，阿帕替尼显著改善了预处理的晚期肝细胞癌患者的总生存期，安全性可管理。
江苏恒瑞医药。
