Liu Quan, Xu Juan-Ying, Xu Ye-Hong, Chen Meng, Deng Li-Chun, Wu Jian-Ping, Zhou Tong, Zhang Li-Qin, Tan Jie, Pu Xing-Xiang, Shang Yu-Long, Hua Jun, Li Yuan-Qin, Cai Wei, Gu Yu-Lan, Peng Xing-Chen, Chan Po-Chung, Jabbour Salma K, Nam Hae-Seong, Hua Dong
Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China.
Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.
Transl Lung Cancer Res. 2022 May;11(5):832-844. doi: 10.21037/tlcr-22-313.
A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC.
In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964.
From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed.
Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.
对于一线化疗失败的广泛期小细胞肺癌（ES-SCLC）患者，可用的治疗策略有限。阿帕替尼是一种酪氨酸激酶抑制剂（TKI），可选择性抑制血管内皮生长因子受体-2（VEGFR-2），已证明其单独使用、与PD-1抑制剂联合使用或与化疗联合使用时，在ES-SCLC中具有积极的抗肿瘤活性，且耐受性良好。然而，阿帕替尼单药治疗在ES-SCLC二线及以上治疗中的疗效和安全性尚不清楚。
在这项前瞻性、探索性、单臂、多中心研究中，符合条件的患者年龄在18岁及以上，组织学确诊为ES-SCLC，且既往全身治疗进展或不耐受。患者接受阿帕替尼500mg（口服，每日一次，每4周为一个周期）。在1个周期后评估疗效，然后根据实体瘤疗效评价标准（RECIST，1.1版）每2个周期基于计算机断层扫描成像进行评估。主要终点是无进展生存期（PFS）。根据美国国立癌症研究所不良事件通用术语标准4.0（NCI-CTCAE 4.0）评估不良事件（AE）。本研究已在中国临床试验注册中心注册，注册号为ChiCTR-OPC-17013964。
2017年7月28日至2019年6月21日，共筛选62例患者，其中57例可进行疗效和安全性分析。客观缓解率（ORR）为14.3%，疾病控制率（DCR）为79.6%。中位PFS为5.6个月[95%置信区间（CI）：3.3 - 8.0个月]，中位总生存期（OS）为11.2个月（95%CI：7.5 - 24.0个月）。在接受阿帕替尼二线治疗的参与者中，中位PFS和OS分别为6.1个月（CI：2.6 - 7.6个月）和12.0个月（CI：7.9个月至未达到）。所有级别的最常见AE为贫血（36.8%）、高血压（33.3%）、疲劳（31.6%）、血胆红素升高（22.8%）、转氨酶升高（19.3%）和手足综合征（17.54%）。3级AE包括2例（3.5%）高血压和1例（1.8%）疲劳。未观察到4/5级AE。
阿帕替尼在预处理的ES-SCLC患者中显示出令人鼓舞的抗肿瘤活性，且毒性可耐受。有必要进行进一步的大规模研究以证明阿帕替尼的疗效。
