Central nervous system efficacy of furmonertinib versus gefitinib in patients with non–small cell lung cancer with epidermal growth factor receptor mutations: Results from FURLONG study.

Abstract

9101 Background: Furmonertinib (AST2818) is a third-generation epidermal growth factor receptor ( EGFR) tyrosine kinase inhibitor (TKI) with central nervous system (CNS) penetration. Here we report the CNS response to furmonertinib versus gefitinib as first-line therapy in EGFR-mutated non-small cell lung cancer (NSCLC) patients in the FURLONG study. Methods: FURLONG was a randomized, double-blind, multi-center phase III study. Patients were randomized 1:1 to receive first-line furmonertinib 80mg/d or gefitinib 250mg/d. Brain scan was mandatory at screening. Patients with asymptomatic CNS metastases who did not require steroid treatment for 28 days or more were enrolled. A pre-planned CNS efficacy analysis was done using RECIST v1.1 in patients with measurable or non-measurable CNS lesions (cFAS) and patients with only measurable CNS lesions (cEFR). Results: Of 358 enrolled patients in the FURLONG study, 133 (37%) patients were defined as cFAS and 60 (17%) were defined as cEFR according to baseline brain scan judged by a blinded independent review committee (IRC). At the cut-off date of Sep 15, 2021, CNS progression-free survival (PFS) assessed by IRC in the cFAS population was significantly longer in the furmonertinib group than in the gefitinib group (20.8 vs 9.8 months, HR 0.40 [95% 0.23-0.71]; p = 0.0011). CNS PFS rate at 6, 12, 18 months were 91%, 77%, 63% in the furmonertinib group, and 76%, 46%, 34% in the gefitinib group. In the cEFR set, confirmed CNS objective response rate was 91% in patients with furmonertinib and 65% in patients with gefitinib (p = 0.0277), and CNS disease control rate were 100% vs 84% (p = 0.9420), respectively. The mean best percentage change in the sum of target CNS lesion size from baseline in cEFR was -61.8% in the furmonertinib group versus -38.7% in the gefitinib group (p = 0.0011). Conclusions: Furmonertinib showed CNS efficacy as first-line therapy in EGFR-mutated NSCLC patients with CNS lesions. Patients treated with furmonertinib had a reduced risk of CNS progression or death, a higher CNS ORR and a deeper CNS response compared with gefitinib. Clinical trial information: NCT03787992.

Annual progress of clinical research on targeted therapy for nonsmall cell lung cancer in 2022

“…In the Chinese Phase III trial FURLONG [ 4 ], compared with gefitinib, the third‐generation EGFR‐TKI furmonertinib in the first‐line treatment of NSCLC with sensitive EGFR mutations can significantly prolong the median progression‐free survival (PFS) (19.3 months vs. 9.9 months, HR = 0.46) and central nervous system PFS (20.8 months vs. 9.8 months, HR = 0.40). Similarly, other third‐generation EGFR‐TKIs, aumolertinib, and nazartinib showed promising results in the AENEAS study [ 5 ] and NCT02108964, respectively, with the median PFS of aumolertinib and nazartinib being 19.3 and 18.0 months, respectively.…”

Adjuvant therapies in stages I–III epidermal growth factor receptor-mutated lung cancer: current and future perspectives

“…Furthermore, aumolertinib demonstrated significantly prolonged median CNS PFS compared with gefitinib (CNS PFS HR, 0.30; 95% CI: 0.137–0.657) ( 90 ). In the phase III FURLONG study, furmonertinib treatment has also demonstrated significantly longer CNS PFS compared with gefitinib (CNS PFS HR, 0.40; 95% CI: 0.23–0.71) ( 91 ). However, overall survival benefit is yet to be demonstrated in these studies.…”

Novel systemic therapies in the management of tyrosine kinase inhibitor-pretreated patients with epidermal growth factor receptor-mutant non-small-cell lung cancer

“… 21 , 118 Two other third-generation EGFR-TKIs, aumolertinib and furmonertinib, also showed prominent CNS activity in first-line treatment. 119 , 120 In the ANEAS trial, the ORR of aumolertinib in evaluable CNS lesions was 85.7%, and the median CNS-PFS was 29.0 months. In the FURLONG study of furmonertinib, the ORR of measurable CNS lesions was 91%, and the duration of response was 100%.…”