Shi Yuankai, Chen Gongyan, Wang Xiang, Liu Yunpeng, Wu Lin, Hao Yanrong, Liu Chunling, Zhu Shuyang, Zhang Xiaodong, Li Yuping, Liu Jiwei, Cao Lejie, Cheng Ying, Zhao Hui, Zhang Shucai, Zang Aimin, Cui Jiuwei, Feng Jian, Yang Nong, Hu Jie, Liu Fei, Jiang Yong, Ge Nan
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.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, the People's Republic of China.
Lancet Reg Health West Pac. 2024 Jun 17;48:101122. doi: 10.1016/j.lanwpc.2024.101122. eCollection 2024 Jul.
Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor () mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO).
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.
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.
In patients with locally advanced or metastatic mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib.
Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).
在FURLONG研究中，对于表皮生长因子受体（EGFR）突变阳性的非小细胞肺癌（NSCLC）患者，伏美替尼作为一线治疗药物，其疗效优于吉非替尼。在此，我们展示预先设定的患者报告结局（PRO）这一次要终点。
在这项多中心、双盲、双模拟、随机3期研究中，患者按1:1随机分配，分别接受每日一次80毫克伏美替尼或每日一次250毫克吉非替尼治疗。使用重复测量混合模型和事件发生时间分析方法，对通过欧洲癌症研究与治疗组织生活质量核心问卷30（EORTC QLQ-C30）和肺癌生活质量问卷13（EORTC QLQ-LC13）评估的PRO进行分析。得分差异10分及以上被视为具有临床相关性。
357例患者（伏美替尼组，n = 178；吉非替尼组，n = 179）接受了至少一剂研究药物治疗，所有患者均完成了至少一次PRO评估。与基线相比，总体得分变化的统计学显著差异显示，伏美替尼在身体功能方面更具优势（组间差异2.14 [95%CI 0.25 - 4.04]，p = 0.027）、恶心/呕吐（-1.56 [95%CI -2.62至-0.49]，p = 0.004）、食欲减退（-2.24 [95%CI -4.26至-0.23]，p = 0.029）、腹泻（-3.36 [95%CI -5.19至-1.54]，p < 0.001）、脱发（-2.62 [95%CI -4.54至-0.71]，p = 0.007）以及其他部位疼痛（-4.55 [95%CI -7.37至-1.74]，p = 0.002），但未达到临床相关性。与吉非替尼相比，伏美替尼使身体功能（风险比0.63 [95%CI 0.42 - 0.94]，p = 0.021）、认知功能（0.73 [95%CI 0.54 - 0.98]，p = 0.034）、恶心/呕吐（0.64 [95%CI 0.41 - 0.99]，p = 0.042）、食欲减退（0.63 [95%CI 0.43 - 0.92]，p = 0.016）、腹泻（0.63 [95%CI 0.46 - 0.85]，p = 0.002）、呼吸困难（0.72 [95%CI 0.53 - 0.98]，p = 0.034）、咳嗽（0.67 [95%CI 0.44 - 1.00]，p = 0.049）、吞咽困难（0.54 [95%CI 0.35 - 0.83]，p = 0.004）和脱发（0.62 [95%CI 0.42 - 0.90]，p = 0.012）恶化的时间更长。
在局部晚期或转移性EGFR突变阳性NSCLC患者中，与吉非替尼相比，伏美替尼在多项功能和症状方面得分有所改善，且恶化延迟。
上海艾力斯医药科技股份有限公司和国家重大新药创制科技重大专项（2017ZX09304015）
