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,The Lancet Respiratory Medicine

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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
The Lancet Respiratory Medicine ( IF 76.2 ) Pub Date : 2022-06-02 , DOI: 10.1016/s2213-2600(22)00168-0
Yuankai Shi ₁ , Gongyan Chen ₂ , Xiang Wang ₃ , Yunpeng Liu ₄ , Lin Wu ₅ , Yanrong Hao ₆ , Chunling Liu ₇ , Shuyang Zhu ₈ , Xiaodong Zhang ₉ , Yuping Li ₁₀ , Jiwei Liu ₁₁ , Lejie Cao ₁₂ , Ying Cheng ₁₃ , Hui Zhao ₁₄ , Shucai Zhang ₁₅ , Aimin Zang ₁₆ , Jiuwei Cui ₁₇ , Jian Feng ₁₈ , Nong Yang ₁₉ , Fei Liu ₂₀ , Yong Jiang ₂₀ , Chuan Gu ₂₀ ,

Affiliation

Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center and National Clinical Research Center for Cancer and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, China.
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Thoracic Medicine Department II, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Department of Medical Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Department of Pulmonary Medicine, Cancer Hospital of Xinjiang Medical University, Urumqi, China.
Department of Respiratory Medicine, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
Department of Medical Oncology, Nantong Cancer Hospital, Nantong, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Respiratory Medicine, The First Affiliated Hospital of USTC, Hefei, China.
Department of Oncology, Jilin Cancer Hospital, Changchun, China.
Department of Respiratory and Critical Care Medicine, The Second Hospital of Anhui University, Hefei, China.
Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Oncology Institute, Beijing, China.
Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, China.
Cancer Center, The First Hospital of Jilin University, Changchun, China.
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Shanghai Allist Pharmaceuticals, Shanghai, China.

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 or older 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 central laboratory. 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 oral gefitinib (250 mg/day) in 21-day cycles until disease progression, the occurrence of intolerable toxicities, withdrawal of consent, or other discontinuation reasons judged by the investigators. Investigators, clinicians, participants, independent review centre (IRC) members, the sponsor, and those analysing the data were all masked to treatment allocation. The primary endpoint was IRC-assessed progression-free survival and, along with safety, was analysed in the full analysis set, which comprised all randomly assigned patients who had received at least one dose of study drug. This study 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 and were 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. Median IRC-assessed progression-free survival was 20·8 months (95% CI 17·8–23·5) in the furmonertinib group and 11·1 months (9·7–12·5) in the gefitinib group (hazard ratio 0·44, 95% CI 0·34–0·58; p<0·0001). Treatment-related adverse events of a grade 3 or more occurred in 20 (11%) of 178 patients in the furmonertinib group and in 32 (18%) of 179 patients in the gefitinib group. Treatment-related serious adverse events were reported in ten (6%) patients in the furmonertinib group and in 11 (6%) patients in the gefitinib group. Ten (6%) patients in the furmonertinib group and three (2%) patients in the gefitinib group died due to adverse events, which were all judged to be possibly unrelated to 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.