Wang Chenchen, Huang Mingzhu, Geng Qirong, Li Wenhua, Chang Jinjia, Tang Wei, Guo Weijian
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
Ther Adv Med Oncol. 2021 Aug 31;13:17588359211039047. doi: 10.1177/17588359211039047. eCollection 2021.
There is no standard therapy for metastatic biliary tract carcinoma (BTC) refractory to first-line chemotherapy. Apatinib, a VEGFR2 tyrosine kynase inhibitor, showed an activity against BTC xenografts in preclinical models. We conducted an exploratory study to evaluate the efficacy and safety of apatinib in patients with metastatic BTC.
This is a single-arm phase II study [ClinicalTrials.gov identifier: NCT03427242]. Eligible patients were aged 18 years or older; histologically confirmed metastatic BTC; refractory or intolerance to at least one chemotherapeutic regimen; no prior use of anti-angiogenic targeted drugs; Eastern Cooperative Oncology Group performance status of 0-2. Patients received oral apatinib 500 mg each day continuously until unacceptable toxicity or tumor progression. The primary endpoint was progress free survival (PFS). The secondary endpoint was overall survival (OS), objective response rate (ORR) and treatment safety.
A total of 22 patients were recruited. All of them received apatinib medication. The median age was 63 (44-75) years old. Twenty patients received efficacy evaluation after treatment. The objective response rate (ORR) and disease control rate (DCR) were 15.0% and 60.0%, respectively. The median PFS was 2.73 months [95% confidence interval (CI): 1.74-3.72 months], with 6 months PFS rate of 27.3% (95% CI: 8.7-45.9%). The median OS was 4.81 months (95% CI: 3.16-10.9 months), with 12 months OS rate of 36.4% (95% CI: 16.2-56.6%). Nine out of 22 patients (40.9%) had grade 3/4 adverse events. The most common grade 3/4 adverse events were hand-foot skin syndrome [three (13.6%) patients] and hypertension [two (9.1%) patients]. No treatment-related death occurred.
For patients with metastatic BTC, apatinib showed an anti-tumor activity with acceptable safety, which deserves the further clinical trial.This trial was prospectively registered on ClinicalTrials.gov [NCT03427242]. Date of first patient enrollment: 26 January 2018. Date of registration (date of first posted): 9 February 2018.
对于一线化疗难治的转移性胆管癌（BTC），尚无标准治疗方案。阿帕替尼是一种血管内皮生长因子受体2（VEGFR2）酪氨酸激酶抑制剂，在临床前模型中显示出对BTC异种移植瘤有活性。我们进行了一项探索性研究，以评估阿帕替尼在转移性BTC患者中的疗效和安全性。
这是一项单臂II期研究[ClinicalTrials.gov标识符：NCT03427242]。符合条件的患者年龄在18岁及以上；组织学确诊为转移性BTC；对至少一种化疗方案难治或不耐受；既往未使用过抗血管生成靶向药物；东部肿瘤协作组（ECOG）体能状态为0 - 2。患者每天持续口服阿帕替尼500mg，直至出现不可接受的毒性或肿瘤进展。主要终点是无进展生存期（PFS）。次要终点是总生存期（OS）、客观缓解率（ORR）和治疗安全性。
共招募了22例患者。他们均接受了阿帕替尼治疗。中位年龄为63（44 - 75）岁。20例患者在治疗后接受了疗效评估。客观缓解率（ORR）和疾病控制率（DCR）分别为15.0%和60.0%。中位PFS为2.73个月[95%置信区间（CI）：1.74 - 3.72个月]，6个月PFS率为27.3%（95%CI：8.7 - 45.9%）。中位OS为4.81个月（95%CI：3.16 - 月），12个月OS率为36.4%（95%CI：16.2 - 56.6%）。22例患者中有9例（40.9%）发生3/4级不良事件。最常见的3/4级不良事件是手足皮肤综合征[3例（13.6%）患者]和高血压[2例（9.1%）患者]。未发生与治疗相关的死亡。
对于转移性BTC患者，阿帕替尼显示出抗肿瘤活性且安全性可接受，值得进一步开展临床试验。本试验已在ClinicalTrials.gov上进行前瞻性注册[NCT03427242]。首例患者入组日期：2018年1月26日。注册日期（首次发布日期）：2018年2月9日。
