Patient-reported outcomes for the phase 3 FURLONG study of furmonertinib versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer

Yuankai Shi; Gongyan Chen; Xiang Wang; Yunpeng Liu; Lin Wu; Yanrong Hao; Chunling Liu; Shuyang Zhu; Xiaodong Zhang; Yuping Li; Jiwei Liu; Lejie Cao; Ying Cheng; Hui Zhao; Shucai Zhang; Aimin Zang; Jiuwei Cui; Jian Feng; Nong Yang; Jie Hu; Fei Liu; Yong Jiang; Nan Ge

doi:10.1016/j.lanwpc.2024.101122

Patient-reported outcomes for the phase 3 FURLONG study of furmonertinib versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer

Lancet Reg Health West Pac. 2024 Jun 17:48:101122. doi: 10.1016/j.lanwpc.2024.101122. eCollection 2024 Jul.

Authors

Yuankai Shi¹, Gongyan Chen², Xiang Wang³, Yunpeng Liu⁴, Lin Wu⁵, Yanrong Hao⁶, Chunling Liu⁷, Shuyang Zhu⁸, Xiaodong Zhang⁹, Yuping Li¹⁰, Jiwei Liu¹¹, Lejie Cao¹², Ying Cheng¹³, Hui Zhao¹⁴, Shucai Zhang¹⁵, Aimin Zang¹⁶, Jiuwei Cui¹⁷, Jian Feng¹⁸, Nong Yang¹⁹, Jie Hu²⁰, Fei Liu²⁰, Yong Jiang²⁰, Nan Ge²⁰

Affiliations

¹ Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, the People's Republic of China.
² Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, the People's Republic of China.
³ Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, the People's Republic of China.
⁴ Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, the People's Republic of China.
⁵ Thoracic Medicine Department II, Hunan Cancer Hospital, Changsha, Hunan, 410013, the People's Republic of China.
⁶ Department of Medical Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, the People's Republic of China.
⁷ Department of Pulmonary Medicine, Cancer Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830000, the People's Republic of China.
⁸ Department of Respiratory Medicine, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221006, the People's Republic of China.
⁹ Department of Medical Oncology, Nantong Cancer Hospital, Nantong, Jiangsu, 226361, the People's Republic of China.
¹⁰ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, the People's Republic of China.
¹¹ Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, the People's Republic of China.
¹² Department of Respiratory Medicine, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, 230001, the People's Republic of China.
¹³ Department of Oncology, Jilin Cancer Hospital, Changchun, Jilin, 130021, the People's Republic of China.
¹⁴ Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui University, Hefei, Anhui, 230601, the People's Republic of China.
¹⁵ Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, 101149, the People's Republic of China.
¹⁶ Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, the People's Republic of China.
¹⁷ Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, 130021, the People's Republic of China.
¹⁸ Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, the People's Republic of China.
¹⁹ Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Changsha, Hunan, 410013, the People's Republic of China.
²⁰ Shanghai Allist Pharmaceutical Technology Co., Ltd, Shanghai, 201318, the People's Republic of China.

Abstract

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO).

Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant.

Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib.

Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib.

Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Keywords: AST2818; Epidermal growth factor receptor; Furmonertinib; Non-small cell lung cancer; Patient-reported outcomes.