Volume 9 Issue 9, Sep 2024:
Article
Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial
Hua-Qiang Zhou
ORCID: orcid.org/0000-0003-3538-4481,Ya-Xiong Zhang
ORCID: orcid.org/0000-0002-3632-0300,Gang Chen,Qi-Tao Yu,Hua Zhang,Guo-Wu Wu,Di Wu,Ying-Cheng Lin,Jun-Fei Zhu,Jian-Hua Chen,Xiao-Hua Hu,Bin Lan,Ze-Qiang Zhou,Hai-Feng Lin,Zi-Bing Wang,Xiao-Lin Lei,Suo-Ming Pan,Li-Ming Chen,Jian Zhang,Tian-Dong Kong,Ji-Cheng Yao,Xin Zheng,Feng Li,Li Zhang &…Wen-Feng Fang
Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.
