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

Signal Transduct Target Ther. 2024 Aug 13;9(1):215. doi: 10.1038/s41392-024-01927-9.

Abstract

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • ErbB Receptors* / antagonists & inhibitors
  • ErbB Receptors* / genetics
  • Female
  • Gefitinib* / administration & dosage
  • Gefitinib* / adverse effects
  • Gefitinib* / therapeutic use
  • Humans
  • Indoles* / administration & dosage
  • Indoles* / adverse effects
  • Indoles* / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Quinolines* / therapeutic use
  • Tyrosine Kinase Inhibitors

Substances

  • anlotinib
  • Gefitinib
  • Quinolines
  • Indoles
  • ErbB Receptors
  • EGFR protein, human
  • Protein Kinase Inhibitors
  • Tyrosine Kinase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT04028778