Safety and Efficacy of Low-Dosage Apatinib Monotherapy in Advanced Lung Squamous-Cell Carcinoma: A Prospective Cohort Study.
Safety and Efficacy of Low-Dosage Apatinib Monotherapy in Advanced Lung Squamous-Cell Carcinoma: A Prospective Cohort Study.
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低剂量阿帕替尼单药治疗晚期肺鳞状细胞癌的安全性和有效性：前瞻性队列研究
DOI：
10.2147/ott.s277532
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发表时间：
2020
影响因子：
4
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Geng Q;Shen H;Zhu W;Lu Y;Wang M;Jiang H;Li D
肺鳞状细胞癌（SqCC）是非小细胞肺癌（NSCLC）中第二常见的组织学类型。晚期肺SqCC的治疗选择仍然是未满足的医疗需求。阿帕替尼是一种血管内皮生长因子受体-2（VEGFR-2）的小分子抑制剂，在晚期NSCLC患者的治疗中是有益的。本研究旨在初步评估小剂量阿帕替尼治疗晚期肺SqCC患者的疗效和安全性。在这项单臂、开放标签、化疗药物启动的II期前瞻性研究（ChiCTR 1800019808）中，我们招募了年龄在54-80岁之间的铂类药物难治性或化疗排斥的晚期肺鳞状细胞癌患者。关键排除标准包括大血管受累和咯血量超过20 mL。阿帕替尼初始剂量为250 mg，每日给药一次，直至疾病进展、不可接受的毒性、停药或死亡。主要终点是所有患者的无进展生存期（PFS）。我们根据接受的治疗评估不良事件。2015年6月11日至2018年8月29日期间入组了38例患者。2例患者因个人原因未能评价治疗疗效，因此36例患者有资格评价阿帕替尼的肿瘤缓解。中位PFS为4.9个月（95% CI：3.0-6.8个月）。6例患者达到部分缓解（PR），客观缓解率（ORR）为16.7%（6/36），总疾病控制率（DCR）为77.8%（28/36）。随访至2020年3月，38例患者中死亡35例，1年生存率为21.1%（8/38）。中位总生存期（OS）为6.9个月（95%CI：5.2-8.5个月）。最常见的不良反应为疲乏（50.0%）、高血压（42.1%）、蛋白尿（23.7%）、食欲不振（23.1%）和手足反应（21.1%）。未发生4级不良反应或药物相关死亡。低剂量阿帕替尼单药治疗可能是晚期肺鳞癌患者的一种选择。
Lung squamous-cell carcinoma (SqCC) is the second most common histology in non-small-cell lung carcinomas (NSCLCs). The treatment options for advanced lung SqCC are still an unmet medical need. Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), is beneficial in the therapy of advanced NSCLC patients. This study aimed to preliminarily assess the efficacy and safety of low-dosage apatinib in patients with advanced lung SqCC. In this single-arm, open-label, investigator-initiated phase II prospective study (ChiCTR1800019808), we enrolled patients aged 54–80 years with platinum-refractory or chemotherapy rejected advanced lung squamous-cell carcinoma. Key exclusion criteria included major blood vessel involvement and gross hemoptysis with an amount of more than 20 mL. Apatinib at an initial dose of 250 mg was administered to patients once daily until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was progression-free survival (PFS) in all patients. We assessed the adverse events according to the treatment received. Thirty-eight patients were enrolled between June 11, 2015 and August 29, 2018. Two patients failed to evaluate treatment efficacy for personal reasons, and thus 36 patients were eligible for evaluation of tumor response to apatinib. Median PFS was 4.9 months (95% CI: 3.0–6.8 months). Six patients achieved partial response (PR); the objective response rate (ORR) was 16.7% (6/36), and the total disease control rate (DCR) was 77.8% (28/36). Followed up to March 2020, 35 of the 38 patients were dead, and the 1-year survival rate was 21.1% (8/38). The median overall survival (OS) was 6.9 months (95% CI: 5.2–8.5 months). The most common adverse events included fatigue (50.0%), hypertension (42.1%), proteinuria (23.7%), loss of appetite (23.1%) and hand-foot reaction (21.1%). No grade 4 adverse effect or drug-related mortality occurred. Low-dose apatinib monotherapy might be an option for patients with advanced lung squamous-cell carcinoma.