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.
- 2024-08-13
- Signal transduction and targeted therapy 9(1)
- Hua-Qiang Zhou
- Ya-Xiong Zhang
- 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
- PubMed: 39134529
- DOI: 10.1038/s41392-024-01927-9
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 315
- Population
- 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC)
- Methods
- phase 3 study, randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle
- Blinding
- Double-blind
- Funding
- Unclear
- Large Human 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.