Furmonertinib superior to gefitinib as first-line treatment for EGFR-mutated NSCLC

In the phase III FURLONG study, the safety and efficacy of furmonertinib was compared to that of gefitinib in patients with non-small cell lung cancer (NSCLC) and EGFR-sensitising mutations. In this multicentre, Chinese trial, furmonertinib significantly prolonged progression-free survival and showed less grade ≥3 treatment-related adverse events compared with gefitinib as first-line treatment in advanced EGFR-mutated NSCLC patients.

Furmonertinib (AST2818) is an irreversible, selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The FURLONG study aimed to compare the efficacy and safety of furmonertinib versus gefitinib in untreated advanced non-small cell lung cancer (NSCLC) patients with EGFR sensitising mutations.

FURLONG study design

FURLONG was a randomised, double-blind, phase III study conducted in 55 centres across mainland China. Stage IIIB/IIIC/IV NSCLC patients with EGFR exon 19 deletions or L858R mutations were randomised (1:1) to receive either furmonertinib 80 mg/day or gefitinib 250 mg/day as first-line therapy. Asymptomatic central nervous system (CNS) metastases were allowed. Treatment was given until disease progression, intolerable toxicity, initiation of new therapy or withdrawal of consent. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC).

Results

In total, 358 patients were randomised to receive furmonertinib (N= 178) or gefitinib (N= 180) treatment. Patient’s baseline characteristics were well-balanced between the two groups. Of note, in the furmonertinib and gefitinib groups, respectively 35% and 32% had central nervous system (CNS) metastases at baseline. As of September 15, 2021, the median follow-up was 21.0 months in each group. The median PFS with furmonertinib was significantly longer than with gefitinib (20.8 versus 11.1 months; HR[95%CI]: 0.44[0.34-0.58]; p< 0.0001). The clinical benefit of PFS was consistent across all pre-specified subgroups, including patients with CNS metastases (HR[95%CI]: 0.50[0.32-0.80], p= 0.0028). Furthermore, furmonertinib significantly prolonged the duration of response (19.7 vs. 10.5 months, HR[95%CI]: 0.39[0.29-0.52], p< 0.0001) and time to progression (20.9 vs. 11.2 months, HR[95%CI]: 0.41[0.31-0.55],  p< 0.0001) as compared with gefitinib. As for objective response rate, disease control rate and depth of response, the results were not statistically significant different. Overall survival was not mature at this analysis. The median duration of exposure was 18.3 months in the furmonertinib group and 11.2 months in the gefitinib group, whereas the frequency of grade ≥3 treatment-related adverse events (TRAEs) was 11% in the furmonertinib group and 18% in the gefitinib group. The most common TRAEs with furmonertinib were elevated ALT, diarrhoea, elevated AST and rash, which were all of lower incidence than in the gefitinib arm.

Conclusion

In this randomised, double-blind, phase III, FURLONG study, furmonertinib was associated with a significantly longer PFS compared with gefitinib in untreated EGFR-mutated NSCLC. This benefit was consistent across prespecified subgroups. Despite a longer duration of exposure, furmonertinib showed an overall favourable safety profile versus gefitinib, with relatively lower frequency of grade ≥3 TRAEs, diarrhoea, rash and liver abnormalities. These results suggest that furmonertinib is a potential first-line therapy in EGFR-mutated Chinese NSCLC patients.

Reference

Shi Yuan-Kai, et al. Furmonertinib versus gefitinib in treatment-naïve EGFR mutated non-small cell lung cancer: a randomized, double-blind, multi-center, phase III study (FURLONG). Presented at ELCC 2022; Abstract 1O.