Ma Yuxiang, Chen Qun, Zhang Yang, Xue Jinhui, Liu Qianwen, Zhao Yuanyuan, Yang Yunpeng, Huang Yan, Fang Wenfeng, Hou Zhiguo, Li Shaorong, Wang Jing, Zhang Li, Zhao Hongyun
Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 651 Dongfeng Road East, Guangdong, 510060, Guangzhou, China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 651 Dongfeng Road East, Guangdong, 510060, Guangzhou, China.
Cancer Chemother Pharmacol. 2023 Nov;92(5):411-418. doi: 10.1007/s00280-023-04563-2. Epub 2023 Jul 31.
Apatinib combined with gefitinib was proven to benefit advanced EGFR-mutant NSCLC patients in first-line treatment. This study aimed to evaluate the drug-drug interaction of gefitinib and apatinib when coadministered in EGFR-mutated NSCLC patients.
In this phase 1b, multi-center, open-label, fixed-sequence study, the drug-drug interaction of gefitinib and apatinib was evaluated when coadministered in EGFR-mutated NSCLC patients. Patients received single-agent apatinib 500 mg QD on days 1-4. Gefitinib 250 mg QD was given on days 5-15 and combined with apatinib 500 mg QD on days 12-15. Serial blood samples were drawn on days 4 and 15. The plasma concentrations and other pharmacokinetics parameters were measured for apatinib with and without gefitinib.
The study enrolled 22 patients and 20 were analyzed for pharmacokinetics. There were no distinct differences in apatinib C and AUC with versus without gefitinib (geometric LSM ratio, 0.96 [90% CI 0.84-1.10] for C and 1.12 [90% CI 0.96-1.30] for AUC). Similar PFS and grade of treatment-emergent adverse events (TEAEs) were found between different C and AUC of apatinib and gefitinib at 500 mg apatinib and 250 mg gefitinib dose levels.
Apatinib pharmacokinetics parameters were not significantly changed when coadministered with gefitinib. All TEAEs were manageable, and there was no need to change the dose level when combining apatinib and gefitinib (ClinicalTrials.gov identifier: NCT04390984, May 18, 2020).
阿帕替尼联合吉非替尼已被证明可使一线治疗的晚期EGFR突变型非小细胞肺癌（NSCLC）患者获益。本研究旨在评估吉非替尼和阿帕替尼在EGFR突变型NSCLC患者中联合使用时的药物相互作用。
在这项1b期、多中心、开放标签、固定顺序研究中，评估了吉非替尼和阿帕替尼在EGFR突变型NSCLC患者中联合使用时的药物相互作用。患者在第1 - 4天接受单药阿帕替尼500 mg每日一次。在第5 - 15天给予吉非替尼250 mg每日一次，并在第12 - 15天与阿帕替尼500 mg每日一次联合使用。在第4天和第15天采集系列血样。测量了阿帕替尼在有和没有吉非替尼情况下的血浆浓度及其他药代动力学参数。
该研究纳入了22例患者，其中20例进行了药代动力学分析。有吉非替尼和没有吉非替尼时阿帕替尼的Cmax和AUC没有明显差异（Cmax的几何最小二乘均值比为0.96 [90%CI 0.84 - 1.10]，AUC的几何最小二乘均值比为1.12 [90%CI 0.96 - 1.30]）。在阿帕替尼500 mg和吉非替尼250 mg剂量水平下，不同Cmax和AUC的阿帕替尼与吉非替尼之间的无进展生存期（PFS）和治疗中出现的不良事件（TEAE）分级相似。
阿帕替尼与吉非替尼联合使用时，其药代动力学参数没有显著变化。所有TEAE均可控，联合使用阿帕替尼和吉非替尼时无需改变剂量水平（ClinicalTrials.gov标识符：NCT04390984，2020年5月18日）。
