AUTHOR=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 

TITLE=Chinese Herbal Medicine Combined With EGFR-TKI in EGFR Mutation-Positive Advanced Pulmonary Adenocarcinoma (CATLA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00732

DOI=10.3389/fphar.2019.00732

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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, <italic>N</italic> = 185) or EGFR-TKI plus placebo (TKI+placebo, <italic>N</italic> = 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.</p><p><bold>Results:</bold> 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; <italic>P</italic> = 0.0064). The subgroup analyses favored TKI+CHM as a first-line treatment (15.97 <italic>vs.</italic> 10.97 months, <italic>P</italic> = 0.0447) rather than as a second-line treatment (11.43 <italic>vs.</italic> 9.23 months, <italic>P</italic> = 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% <italic>vs.</italic> 52.66%, <italic>P</italic> = 0.026) and QoL. Drug-related grade 1–2 adverse events were less common with TKI+CHM.</p><p><bold>Conclusions:</bold> TKI+CHM improved PFS when compared with TKI alone in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).</p><p>Clinical Trial Registration: <uri xlink:href="http://www.clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">www.ClinicalTrials.gov</uri>, identifier NCT01745302.</p>