Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study
Mené en Chine sur 358 patients atteints d'un cancer du poumon non à petites cellules de stade localement avancé ou métastatique et présentant une mutation du gène EGFR (durée médiane de suivi : 21 mois), cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du géfitinib et du furmonertinib (un inhibiteur de tyrosine kinase de l'EGFR de troisième génération) en traitement de première ligne
Résumé en anglais
Background : Furmonertinib (AST2818) is an irreversible, selective, third-generation EGFR tyrosine-kinase inhibitor. We aimed to investigate the efficacy and safety of furmonertinib versus the first-generation EGFR tyrosine-kinase inhibitor gefitinib as first-line treatment in patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC).
Methods : The FURLONG study is a multicentre, double-blind, randomised, phase 3 study done in 55 hospitals across mainland China. We enrolled patients who were aged 18 years orolder and had histologically confirmed, locally advanced or metastatic, stage IIIB,IIIC, or IV unresectable NSCLC with EGFR exon 19 deletions or exon 21 Leu858Arg mutation on tissue biopsy confirmed by a centrallaboratory. Eligible patients were stratified according to EGFR mutation (exon 19 deletions or exon 21 Leu858Arg) and CNS metastases (with or without)and randomly assigned (1:1) to receive either oral furmonertinib (80 mg/day) or oralgefitinib (250 mg/day) in 21-day cycles until disease progression, the occurrenceof intolerable toxicities, withdrawal of consent, or other discontinuation reasonsjudged by the investigators. Investigators, clinicians, participants, independentreview centre (IRC) members, the sponsor, and those analysing the data were all maskedto treatment allocation. The primary endpoint was IRC-assessed progression-free survival and, along with safety, was analysed in the full analysis set, which comprised allrandomly assigned patients who had received at least one dose of study drug. Thisstudy is registered with ClinicalTrials.gov, NCT03787992, and is ongoing for survival follow-up.
Findings : Between May 30, 2019, and Dec 5, 2019, 750 patients were screened, of whom 358 were randomly assigned to receive either furmonertinib and gefitinib-matching placebo (n=178) or gefitinib and furmonertinib-matching placebo (n=180). 178 patients randomly assigned to furmonertinib and 179 patients randomly assigned to gefitinib were treated andwere included in the full analysis set. Median follow-up was 21·0 months (IQR 18·0–23·5)in the furmonertinib group and 21·0 months (18·0–23·5) in the gefitinib group. MedianIRC-assessed progression-free survival was 20·8 months (95% CI 17·8–23·5) in the furmonertinibgroup and 11·1 months (9·7–12·5) in the gefitinib group (hazard ratio 0·44, 95% CI0·34–0·58; p<0·0001). Treatment-related adverse events of a grade 3 or more occurredin 20 (11%) of 178 patients in the furmonertinib group and in 32 (18%) of 179 patientsin the gefitinib group. Treatment-related serious adverse events were reported inten (6%) patients in the furmonertinib group and in 11 (6%) patients in the gefitinibgroup. Ten (6%) patients in the furmonertinib group and three (2%) patients in thegefitinib group died due to adverse events, which were all judged to be possibly unrelatedto study treatment by the investigators.
Interpretation : Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive NSCLC, along with an acceptable safety profile without new signals. Furmonertinib is a new potential treatment option for this population.
