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

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.