Central Nervous System Efficacy of Furmonertinib (AST2818) Versus Gefitinib as First-Line Treatment for EGFR-Mutated
Yuankai Shi1, Gongyan Chen2, Xiang Wang3
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China.
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.
Insights
Furmonertinib demonstrates superior efficacy over gefitinib in treating brain metastases for patients with EGFR-mutated non-small cell lung cancer (NSCLC). This pan-EGFR tyrosine kinase inhibitor significantly improves CNS progression-free survival and response rates.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Non-small cell lung cancer (NSCLC) with EGFR-sensitizing mutations often develops central nervous system (CNS) metastases.
- Tyrosine kinase inhibitors targeting EGFR are crucial in NSCLC treatment, but CNS efficacy varies.
- Furmonertinib is a novel pan-EGFR inhibitor investigated for its antitumor activity, including in the CNS.
Purpose of the Study:
- To compare the central nervous system (CNS) efficacy of furmonertinib versus gefitinib in untreated EGFR-sensitizing mutation-positive NSCLC patients with CNS metastases.
- To evaluate key CNS efficacy endpoints, including progression-free survival, objective response rate, and depth of response.
Main Methods:
- The FURLONG study was a randomized, double-blind, phase 3 trial conducted in China.
- 133 patients with asymptomatic steady CNS metastases at baseline were included in this preplanned CNS subgroup analysis.
- Patients received either furmonertinib 80 mg once daily or gefitinib 250 mg once daily.
Main Results:
- Furmonertinib significantly improved CNS progression-free survival (20.8 months vs. 9.8 months; HR=0.40, p=0.0011).
- CNS objective response rate was higher with furmonertinib (91% vs. 65%; OR=6.82, p=0.0277) in patients with measurable CNS lesions.
- Furmonertinib achieved a greater least-square mean CNS depth of response (62% vs. 39%; p=0.0011).
Conclusions:
- First-line furmonertinib treatment demonstrated superior CNS efficacy compared to gefitinib in EGFR-mutated NSCLC patients with CNS metastases.
- Furmonertinib offers a promising therapeutic option for managing brain metastases in this patient population.
- The findings support furmonertinib as a preferred first-line treatment for NSCLC with EGFR mutations and CNS involvement.
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