Jiao Lijing, Xu Jianfang, Sun Jianli, Chen Zhiwei, Gong Yabin, Bi Ling, Lu Yan, Yao Jialin, Zhu Weirong, Hou Aihua, Feng Gaohua, Jia Yingjie, Shen Weisheng, Li Yongjian, Zhang Ziwen, Chen Peiqi, Xu Ling
Institute of Clinical Immunology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2019 Jul 2;10:732. doi: 10.3389/fphar.2019.00732. eCollection 2019.
To determine the clinical activity and safety of Chinese herbal medicine (CHM) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in patients with advanced pulmonary adenocarcinoma (ADC) and the ability of CHM combined with EGFR-TKI to activate EGFR mutations. Three hundred and fifty-four patients were randomly assigned to EGFR-TKI (erlotinib 150 mg/d, gefitinib 250 mg/d, or icotinib 125 mg tid/d) plus CHM (TKI+CHM, = 185) or EGFR-TKI plus placebo (TKI+placebo, = 169). Progression-free survival (PFS) was the primary end point; the secondary end points were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life [Functional Assessment of Cancer Therapy-Lung (FACT-L) and Lung Cancer Symptom Scale (LCSS)], and safety. The median PFS was significantly longer for the TKI+CHM group (13.50 months; 95% CI, 11.20-16.46 months) than with the EGFR-TKI group (10.94 months; 95% CI, 8.97-12.45 months; hazard ratio, 0.68; 95% CI, 0.51-0.90; = 0.0064). The subgroup analyses favored TKI+CHM as a first-line treatment (15.97 10.97 months, = 0.0447) rather than as a second-line treatment (11.43 9.23 months, = 0.0530). Patients with exon 19 deletion had a significantly longer PFS than with 21 L858R. The addition of CHM to TKI significantly improved the ORR (64.32% 52.66%, = 0.026) and QoL. Drug-related grade 1-2 adverse events were less common with TKI+CHM. TKI+CHM improved PFS when compared with TKI alone in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01745302.
为确定中药（CHM）联合表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗晚期肺腺癌（ADC）患者的临床活性和安全性，以及CHM联合EGFR-TKI激活EGFR突变的能力。354例患者被随机分为EGFR-TKI（厄洛替尼150mg/d、吉非替尼250mg/d或埃克替尼125mg每日三次）加CHM组（TKI+CHM，n=185）或EGFR-TKI加安慰剂组（TKI+安慰剂，n=169）。无进展生存期（PFS）是主要终点；次要终点为总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）、生活质量[癌症治疗功能评估-肺癌（FACT-L）和肺癌症状量表（LCSS）]和安全性。TKI+CHM组的中位PFS（13.50个月；95%CI，11.20-16.46个月）显著长于EGFR-TKI组（10.94个月；95%CI，8.97-12.45个月；风险比，0.68；95%CI，0.51-0.90；P=0.0064）。亚组分析显示，TKI+CHM作为一线治疗更具优势（15.97对10.97个月，P=0.0447），而非二线治疗（11.43对9.23个月，P=0.0530）。外显子19缺失患者的PFS显著长于21 L858R患者。TKI联合CHM显著提高了ORR（64.32%对52.66%，P=0.026）和生活质量。TKI+CHM组与药物相关的1-2级不良事件较少见。与单独使用TKI相比，TKI+CHM改善了EGFR突变阳性晚期非小细胞肺癌（NSCLC）患者的PFS。临床试验注册：www.ClinicalTrials.gov，标识符NCT01745302。
