Abstract 667P
Background
CNS metastases is associated with impaired quality of life and shortened survival. Furmonertinib is a third-generation EGFR TKI with wide therapeutic range and well-tolerated safety profile from 40mg to 240mg daily, which can achieve high exposure in the brain. In second or later line setting, furmonertinib 160mg has showed better outcomes in CNS metastases patients than 80mg. Thus a multicencer, open-label, single-arm phase II study was conducted to explore furmonertinib 160mg as first-line treatment for metastatic EGFR mutation-positive NSCLC patients with CNS metastases.
Methods
Treatment naive metastatic EGFR mutation-positive NSCLC patients with stable CNS metastases were enrolled. EGFR exon 19 deletion and/or exon 21 L858R mutation were eligible. Regimen was furmonertinib 160mg p.o qd. Primary endpoint was PFS. Secondary endpoints were CNS PFS, ORR, DCR, CNS ORR, CNS DCR and safety.
Results
Between November 2022 and July 2024, 30 patients were enrolled. Median age was 57.5 years (range 33–75), female 60%, ECOG PS 1 83.3%, never smokers 63.3%, EGFR L858R 53.3%. At data cutoff (July 12 2024), median follow-up was 8.2 months, treatment is ongoing in 18 patients and the longest exposure was 19.8 months. Among the 30 patients who received study treatment, 26 of them had at least once tumor response evaluation. Median PFS or median CNS PFS was not reached. ORR was 84.6% (95%CI 65.1% to 95.6%). DCR was 100% (95%CI 86.8% to 100%). CNS ORR was 96.2% (95%CI 80.4% to 99.9%), including 5 CR (5/26, 19.2%). CNS DCR was 100% (95%CI 86.8% to 100%). Only 1 patient experienced grade 3 rash assessed as treatment related adverse event (TRAE), which resulted in dose interruption and dose reduction. No grade 4 or 5 TRAE was reported. No treatment discontinuation due to TRAE was reported.
Conclusions
Furmonertinib 160mg as first-line treatment showed clinically meaningful efficacy and well-tolerated safety profile for metastatic EGFR mutation-positive NSCLC patients with CNS metastases. This study is still ongoing and further analyses of longer-term outcomes will be evaluated, which may provide more evidence to support furmonertinib 160mg treatment is in favor of CNS metastases patients.
Clinical trial identification
NCT05379803.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Shanghai Allist Pharmaceuticals Co., Ltd, Shanghai, China.
Disclosure
All authors have declared no conflicts of interest.