阿帕替尼联合卡培他滨治疗铂类耐药的转移性和/或复发性鼻咽癌的疗效和安全性：一项前瞻性、Ⅱ期试验。
The efficacy and safety of apatinib plus capecitabine in platinum-refractory metastatic and/or recurrent nasopharyngeal carcinoma: a prospective, phase II trial.
机构信息
Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, Guangdong, People's Republic of China.
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
出版信息
BMC Med. 2023 Mar 16;21(1):94. doi: 10.1186/s12916-023-02790-1.
BACKGROUND
Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy.
METHODS
In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon's two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m twice per day on days 1-14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1-52.1) and 85.9% (95% CI, 75.0-93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8-21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0-10.0) and the median OS was 15.7 months (95% CI, 11.3-20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3-4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed.
CONCLUSIONS
Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity.
TRIAL REGISTRATION
Chi-CTR1800017229.
背景
先前的研究表明，口服酪氨酸激酶抑制剂阿帕替尼单药治疗复发性或转移性（RM）鼻咽癌（NPC）患者具有良好的疗效。在这项研究中，我们旨在评估阿帕替尼联合卡培他滨作为二线或二线以上治疗方案，用于治疗一线铂类化疗失败的 RM-NPC 患者的疗效和安全性。
方法
这是一项单臂、二期研究，我们纳入了至少有一个可测量病灶的 RM-NPC 患者，这些病灶根据实体瘤反应评估标准（RECIST v1.1）进行评估。采用 Simon 的两阶段设计确定样本量。所有患者均接受阿帕替尼 500mg 每日一次和卡培他滨 1000mg/m2 每日两次，每 21 天周期的第 1-14 天给药。主要终点为客观缓解率（ORR），次要终点包括疾病控制率（DCR）、缓解持续时间（DoR）、无进展生存期（PFS）、总生存期（OS）和安全性。
结果
我们于 2018 年 9 月至 2020 年 8 月期间共纳入 64 例患者。ORR 和 DCR 分别为 39.1%（95%CI，27.1-52.1）和 85.9%（95%CI，75.0-93.4）。中位 DoR 为 14.4 个月（95%CI，7.8-21.0）。截至 2021 年 4 月 20 日，中位随访时间为 12.0 个月。中位 PFS 为 7.5 个月（95%CI，5.0-10.0），中位 OS 为 15.7 个月（95%CI，11.3-20.1）。任何级别的最常见毒性是贫血（75.0%）、手足综合征（65.6%）和蛋白尿（64.0%）。3 级-4 级毒性见于 36 例（56.3%）患者，最常见的是高血压（14.1%）、黏膜炎（12.4%）和乏力（10.9%）。
结论
阿帕替尼联合卡培他滨作为预处理铂类难治性 RM-NPC 患者的二线治疗选择具有良好的疗效。考虑到毒性，需要进一步研究这种联合用药的剂量选择。
试验注册
Chi-CTR1800017229。
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