安罗替尼作为表皮生长因子受体（EGFR）突变状态的非小细胞肺癌三线治疗的疗效：ALTER0303随机3期研究的亚组分析
The efficacy of anlotinib as third-line treatment for non-small cell lung cancer by EGFR mutation status: a subgroup analysis of the ALTER0303 randomized phase 3 study.
作者信息
Zhao Yizhuo, Wang Qiming, Zhang Li, Shi Jianhua, Wang Zhehai, Cheng Ying, He Jianxing, Shi Yuankai, Chen Weiqiang, Luo Yi, Wu Lin, Wang Xiuwen, Nan Kejun, Jin Faguang, Dong Jian, Li Baolan, Yamaguchi Fumihiro, Breadner Daniel, Nagano Tatsuya, Tanaka Fumihiro, Husain Hatim, Li Kai, Han Baohui
机构信息
Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
出版信息
Transl Lung Cancer Res. 2022 May;11(5):776-785. doi: 10.21037/tlcr-22-320.
BACKGROUND
Anlotinib demonstrated improved overall survival (OS) and progression-free survival (PFS) compared with placebo as a third-line or subsequent therapy in patients with non-small cell lung cancer (NSCLC) in the ALTER0303 trial. The status of epidermal growth factor receptor (EGFR) mutation, different previous treatment may affect the efficacy of subsequent therapy, and we did this subgroup analysis to characterize the efficacy of anlotinib in patients with and without EGFR mutation.
METHODS
The ALTER0303 trial was a randomized, double-blind, phase 3 study of anlotinib in patients with NSCLC who failed at least 2 lines of treatment. In the study, 138 of 437 randomized patients were EGFR mutation positive. A Cox model was used to examine the influence of previous treatment on the efficacy of anlotinib according to EGFR mutation status.
RESULTS
For patients with EGFR mutation, the OS was 10.7 and 6.3 months (HR 0.59; 95% CI: 0.38-0.94, P=0.025) in the anlotinib and placebo group, respectively. The PFS was 5.6 and 0.8 months (HR 0.21; 95% CI: 0.13-0.32, P<0.0001) in the anlotinib and placebo group, respectively. For patients without EGFR mutation, the OS was 8.9 months for anlotinib and 6.5 months for placebo (HR 0.73; 95% CI: 0.55-0.97, P=0.029), and the PFS was 5.4 months for anlotinib and 1.6 months for placebo (HR 0.29; 95% CI: 0.22-0.39, P<0.0001). In the anlotinib group, the OS and PFS for patients with and without EGFR mutation was 10.7 and 8.9 months (HR 0.69; 95% CI: 0.50-0.95, P=0.021), 5.6 and 5.4 months (HR 1.00; 95% CI: 0.75-1.34, P=1.000), respectively. The incidence of adverse events was similar in subgroups.
CONCLUSIONS
This analysis demonstrated that the benefit of anlotinib as a third-line therapy for patients with NSCLC was independent of EGFR mutation status.
背景
在ALTER0303试验中，与安慰剂相比，安罗替尼作为非小细胞肺癌（NSCLC）患者的三线或后续治疗，可改善总生存期（OS）和无进展生存期（PFS）。表皮生长因子受体（EGFR）突变状态、既往不同治疗可能会影响后续治疗的疗效，因此我们进行了这项亚组分析，以明确安罗替尼在有或无EGFR突变患者中的疗效。
方法
ALTER0303试验是一项针对至少接受过2线治疗失败的NSCLC患者的安罗替尼随机、双盲、3期研究。在该研究中，437例随机分组患者中有138例EGFR突变阳性。采用Cox模型根据EGFR突变状态检验既往治疗对安罗替尼疗效的影响。
结果
对于EGFR突变患者，安罗替尼组和安慰剂组的OS分别为10.7个月和6.3个月（HR=0.59；95%CI：0.38-0.94，P=0.025）。安罗替尼组和安慰剂组的PFS分别为5.6个月和0.8个月（HR=0.21；95%CI：0.13-0.32，P<0.0001）。对于无EGFR突变患者，安罗替尼组的OS为8.9个月，安慰剂组为6.5个月（HR=0.73；95%CI：0.55-0.97，P=0.029），安罗替尼组的PFS为5.4个月，安慰剂组为1.6个月（HR=0.29；95%CI：0.22-0.39，P<0.0001）。在安罗替尼组中，有和无EGFR突变患者的OS和PFS分别为10.7个月和8.9个月（HR=0.69；95%CI：0.50-0.95，P=0.021）、5.6个月和5.4个月（HR=1.00；95%CI：0.75-1.34，P=1.000）。亚组中不良事件的发生率相似。
结论
该分析表明，安罗替尼作为NSCLC患者三线治疗的获益与EGFR突变状态无关。
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