Central Nervous System Efficacy of Furmonertinib (AST2818) Versus Gefitinib as First-Line Treatment for EGFR-Mutated NSCLC: Results From the FURLONG Study.

Abstract

INTRODUCTION:

Furmonertinib (AST2818) is a pan-EGFR tyrosine kinase inhibitor with central nervous system (CNS) antitumor activity. We report the CNS efficacy of furmonertinib compared with gefitinib in untreated EGFR-sensitizing mutation-positive NSCLC from the FURLONG study.

METHODS:

FURLONG was a randomized, double-blind, phase 3 study conducted in 55 hospitals in the People's Republic of China. Patients 1:1 randomly received furmonertinib 80 mg once daily or gefitinib 250 mg once daily treatment. At screening, all the patients underwent brain imaging examination. Patients with asymptomatic steady CNS metastases at baseline constituted this preplanned CNS subgroup analysis.

RESULTS:

A total of 358 patients were enrolled in the FURLONG study. In the 133 (37%) patients who had measurable or nonmeasurable CNS lesions, CNS progression-free survival was 20.8 months (95% confidence interval [CI]: 15.2-25.3) in the furmonertinib group and 9.8 months (95% CI: 7.2-18.0) in the gefitinib group (hazard ratio = 0.40 [95% CI: 0.23-0.71], p = 0.0011). In the 60 patients (17%) who had measurable CNS lesions, CNS objective response rate was 91% (95% CI: 72-99) with furmonertinib and 65% (95% CI: 48-80) with gefitinib (OR = 6.82 [95% CI: 1.23-37.67], p = 0.0277). The least-square mean of CNS depth of response was 62% (95% CI: 51-72) in the furmonertinib group and 39% (95% CI: 30-47) in the gefitinib group, the mean difference was 23% (95% CI: 10-37, p = 0.0011).

CONCLUSIONS:

Furmonertinib first-line treatment was found to have superior efficacy in CNS progression-free survival, CNS objective response rate, and CNS depth of response compared with gefitinib in patients with EGFR-mutated NSCLC with CNS metastases.

• Authors: Yuankai Shi, Gongyan Chen, Xiang Wang, Yunpeng Liu, Lin Wu, Yanrong Hao, Chunling Liu, Shuyang Zhu, Xiaodong Zhang, Yuping Li, Jiwei Liu, Lejie Cao, Ying Cheng, Hui Zhao, Shucai Zhang, Aimin Zang, Jiuwei Cui, Jian Feng, Nong Yang, Fei Liu, Yong Jiang, Chuan Gu
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 17 Issue 11 Pg. 1297-1305 (11 2022) ISSN: 1556-1380 [Electronic] United States
• PMID: 35932953 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Chemical References

• aflutinib
• EGFR protein, human
• ErbB Receptors
• Gefitinib
• Protein Kinase Inhibitors
• Quinazolines

Topics

• Humans
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, chemically induced)
• Central Nervous System
• Disease-Free Survival
• ErbB Receptors (genetics)
• Gefitinib (pharmacology, therapeutic use)
• Lung Neoplasms (drug therapy, genetics, chemically induced)
• Mutation
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Quinazolines