Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Department of Oncology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
JAMA Netw Open. 2020 Mar 2;3(3):e201226. doi: 10.1001/jamanetworkopen.2020.1226.
There is currently no standard treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) without driver gene variation after failure of 2 or more lines of chemotherapy.
To assess the efficacy and safety of apatinib combined with oral vinorelbine.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2 prospective nonrandomized clinical trial evaluating the efficacy and safety of apatinib plus vinorelbine recruited patients from Hunan Cancer Center, Hunan, China, from January 1, 2017, to November 30, 2018. Eligible patients were those with wild-type advanced NSCLC whose disease did not respond to at least 2 lines of chemotherapy. Patients were evaluated until December 31, 2019. Data were analyzed from July 2019 to December 2019.
Apatinib at an initial dose of 500 mg once daily and oral vinorelbine 60 mg/m2 once weekly were administered until disease progression, patient withdrawal, or occurrence of unacceptable toxic effects.
The primary end point was overall response rate. Secondary end points were overall survival, progression-free survival, and safety.
The potential efficacy of apatinib plus vinorelbine was identified using drug susceptibility assay based on 3-dimensional coculture of tumor cells derived from 3 patients with lung adenocarcinoma. Among 30 patients enrolled, the median (range) age was 63 (34-78) years and 18 (60%) were men. Most patients (27 patients [90%]) had stage IV disease, and the median (range) number of prior unsuccessful treatments was 2 (2-5) lines of chemotherapy. Twenty-five patients (83%) completed the treatment, while 5 patients (17%) discontinued treatment owing to intolerable adverse events. The overall response rate was 36.7% (11 patients) and the disease control rate was 76.7% (23 patients). The median progression-free survival was 4.5 (95% CI, 2.4-6.6) months, and the median overall survival was 10.0 (95% CI, 4.8-17.1) months. Hand-foot syndrome was the most common adverse event observed, including grade 3 hand-foot syndrome observed in 5 patients (17%) and grade 4 hand-foot observed in 1 patient (3%). Grade 3 weakness was observed in 1 patient (3%).
These findings suggest that apatinib combined with oral vinorelbine is a potentially effective regimen with an acceptable safety profile. This regimen may have potential as a treatment option for patients with wild-type advanced NSCLC whose disease failed at least 2 prior lines of chemotherapy.
ClinicalTrials.gov Identifier: NCT03652857.
对于二线及以上化疗失败的无驱动基因突变的晚期非小细胞肺癌（NSCLC）患者，目前尚无标准的治疗策略。
评估阿帕替尼联合口服长春瑞滨的疗效和安全性。
设计、地点和参与者：这项评估阿帕替尼联合长春瑞滨疗效和安全性的 2 期前瞻性非随机临床试验，于 2017 年 1 月 1 日至 2018 年 11 月 30 日在中国湖南肿瘤中心招募患者。合格的患者是那些患有野生型晚期 NSCLC 的患者，其疾病对至少 2 线化疗无反应。患者接受评估直至 2019 年 12 月 31 日。数据分析于 2019 年 7 月至 2019 年 12 月进行。
阿帕替尼初始剂量为 500mg/天，长春瑞滨 60mg/m2/周，口服给药，直至疾病进展、患者退出或出现不可接受的毒性。
主要终点为总缓解率。次要终点为总生存期、无进展生存期和安全性。
使用基于 3 例肺腺癌肿瘤细胞的三维共培养的药物敏感性检测，确定了阿帕替尼联合长春瑞滨的潜在疗效。在纳入的 30 例患者中，中位（范围）年龄为 63（34-78）岁，18 例（60%）为男性。大多数患者（27 例[90%]）患有 IV 期疾病，中位（范围）既往治疗失败次数为 2（2-5）线化疗。25 例（83%）患者完成了治疗，而 5 例（17%）因不耐受的不良事件停止治疗。总缓解率为 36.7%（11 例），疾病控制率为 76.7%（23 例）。中位无进展生存期为 4.5（95%CI，2.4-6.6）个月，中位总生存期为 10.0（95%CI，4.8-17.1）个月。手足综合征是最常见的不良事件，包括 5 例（17%）患者出现 3 级手足综合征和 1 例（3%）患者出现 4 级手足综合征。1 例（3%）患者出现 3 级乏力。
这些发现表明，阿帕替尼联合口服长春瑞滨是一种具有潜在疗效且安全性可接受的方案。该方案可能是那些至少接受 2 线化疗失败的野生型晚期 NSCLC 患者的一种潜在治疗选择。
ClinicalTrials.gov 标识符：NCT03652857。
