Yang Guangjian, Xu Haiyan, Yang Lu, Xu Fei, Zhang Shuyang, Yang Yaning, Wang Yan
Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Department of Comprehensive Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Lung Cancer. 2020 Sep;147:229-236. doi: 10.1016/j.lungcan.2020.07.024. Epub 2020 Jul 23.
Apatinib showed efficacy in non-small cell lung cancer (NSCLC). We conducted this phase II clinical study to assess the efficacy and safety of apatinib in combination with pemetrexed-platinum chemotherapy in non-squamous NSCLC (Clinical Trial Registration: ChiCTR1800015920).
Patients received oral apatinib (250 mg/d) with intravenous pemetrexed (500 mg/m)-platinum (carboplatin AUC = 5 or cisplatin 75 mg/m) chemotherapy every 21 days for 6 treatment cycles, and then maintained with apatinib 250 mg/d until progressive disease or intolerable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints included the progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and safety.
Twenty advanced and chemo-naive non-squamous NSCLC patients were enrolled and evaluated. The ORR and DCR was 80% and 100%, respectively. The median PFS (mPFS) and median OS (mOS) for total patients was 7.7 (95%CI: 3.1-12.3) and 20.1 (95%CI: not available, NA) months. In the TKI-pretreated and treatment-naive subgroup, the ORR was 90% vs.70%, and the mPFS was 8.9 (95%CI: 5.5-12.3) vs.5.7 (95%CI: 0.1-11.3) months, respectively (P = 0.433). The mPFS in the responders without central nervous system (CNS) metastasis at baseline was 10.0 (95%CI: 6.1-13.9) months, and it was 3.8 (95%CI: 0.9-6.7) months in those with presence of CNS metastasis at baseline (P = 0.041, HR = 0.283, 95%CI: 0.084-0.948). Toxicities mainly included grade I-II hand-foot syndrome, hypertension, proteinuria and myelosuppression.
Apatinib in combination with pemetrexed-platinum chemotherapy showed good efficacy and tolerable toxicity in advanced non-squamous NSCLC, especially for those who failed to prior TKI targeted therapies.
阿帕替尼在非小细胞肺癌（NSCLC）中显示出疗效。我们开展了这项II期临床研究，以评估阿帕替尼联合培美曲塞-铂类化疗在非鳞状NSCLC中的疗效和安全性（临床试验注册号：ChiCTR1800015920）。
患者接受口服阿帕替尼（250mg/d），并每21天静脉注射培美曲塞（500mg/m²）-铂类（卡铂AUC = 5或顺铂75mg/m²）进行化疗，共6个治疗周期，然后继续使用阿帕替尼250mg/d维持治疗，直至疾病进展或出现无法耐受的毒性。主要终点为客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、疾病控制率（DCR）、总生存期（OS）和安全性。
20例晚期初治非鳞状NSCLC患者入组并接受评估。ORR和DCR分别为80%和100%。所有患者的中位PFS（mPFS）和中位OS（mOS）分别为7.7（95%CI：3.1 - 12.3）个月和20.1（95%CI：不可用，NA）个月。在经TKI预处理和初治亚组中，ORR分别为90%和70%，mPFS分别为8.9（95%CI：5.5 - 12.3）个月和5.7（95%CI：0.1 - 11.3）个月（P = 0.433）。基线时无中枢神经系统（CNS）转移的缓解者的mPFS为10.0（95%CI：6.1 - 13.9）个月，而基线时存在CNS转移者的mPFS为3.8（95%CI：0.9 - 6.7）个月（P = 0.041，HR = 0.283，95%CI：0.084 - 0.948）。毒性主要包括I-II级手足综合征、高血压、蛋白尿和骨髓抑制。
阿帕替尼联合培美曲塞-铂类化疗在晚期非鳞状NSCLC中显示出良好的疗效和可耐受的毒性，尤其对于那些先前TKI靶向治疗失败的患者。
