Shou Jiawei, Chen Jun, Guo Qunyi, Hong Wei, Wang Yonghui, Rao Chuangzhou, Lu Liqin, Yang Xinmei, Zhu Dan, Lan Fen, Fang Yong, Pan Hongming
Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Tumor Radiochemotherapy, The Affiliated People's Hospital of NingBo University, Ningbo, China.
Cancer. 2025 May 15;131(10):e35822. doi: 10.1002/cncr.35822.
The combination of anlotinib with chemotherapy has demonstrated encouraging efficacy in the treatment of nonsmall cell lung cancer (NSCLC). The objective of this phase 1/2 trial was to establish the maximum tolerated dose of anlotinib in combination with docetaxel and to assess the efficacy and safety of this regimen in patients with advanced NSCLC who had progressed after platinum-based chemotherapy.
In the phase 1 trial, eight patients were enrolled to determine the maximum tolerated dose, which was identified as 10 mg for anlotinib in combination with docetaxel. In the phase 2 trial, in total, 88 patients were randomized, with 57 receiving anlotinib at the established maximum tolerated dose alongside docetaxel and 31 receiving docetaxel monotherapy. Tumor response was evaluated in 88 patients.
In the phase 2 study, the combination of anlotinib and docetaxel demonstrated a significant improvement in progression-free survival compared with docetaxel monotherapy (median, 5.39 vs. 2.56 months; hazard ratio, 0.36; 95% confidence interval, 0.21-0.63; p = .0002). The objective response rate was also superior in the combination group (26.32% vs. 6.45%). The median overall survival was 16.82 months for the combination group versus 9.86 months for the monotherapy group (hazard ratio, 0.89; 95% confidence interval, 0.47-1.66; p = .7114). Safety analysis included 96 patients, and the most frequent treatment-emergent adverse events were decreased neutrophil count and decreased white blood cell count.
The addition of anlotinib to docetaxel was characterized by a manageable safety profile and also resulted in a significant improvement in progression-free survival among patients with advanced NSCLC who had previously failed platinum-based chemotherapy (ClinicalTrials.gov identifier NCT03726736).
安罗替尼联合化疗在非小细胞肺癌（NSCLC）治疗中已显示出令人鼓舞的疗效。这项1/2期试验的目的是确定安罗替尼联合多西他赛的最大耐受剂量，并评估该方案对铂类化疗后进展的晚期NSCLC患者的疗效和安全性。
在1期试验中，招募了8名患者以确定最大耐受剂量，安罗替尼联合多西他赛的最大耐受剂量被确定为10 mg。在2期试验中，总共88名患者被随机分组，57名患者接受既定最大耐受剂量的安罗替尼联合多西他赛治疗，31名患者接受多西他赛单药治疗。对88名患者的肿瘤反应进行了评估。
在2期研究中，与多西他赛单药治疗相比，安罗替尼联合多西他赛在无进展生存期方面有显著改善（中位数分别为5.39个月和2.56个月；风险比为0.36；95%置信区间为0.21 - 0.63；p = 0.0002）。联合治疗组的客观缓解率也更高（26.32%对6.45%）。联合治疗组的中位总生存期为16.82个月，单药治疗组为9.86个月（风险比为0.89；95%置信区间为0.47 - 1.66；p = 0.7114）。安全性分析纳入了96名患者，最常见的治疗中出现的不良事件是中性粒细胞计数减少和白细胞计数减少。
在多西他赛基础上加用安罗替尼具有可控的安全性，并且在既往铂类化疗失败的晚期NSCLC患者中，无进展生存期有显著改善（ClinicalTrials.gov标识符NCT03726736）。
