医学
内科学
肝内胆管癌
胃肠病学
临床终点
高磷血症
不利影响
进行性疾病
养生
危险系数
成纤维细胞生长因子受体
临床研究阶段
实体瘤疗效评价标准
肿瘤科
置信区间
化疗
成纤维细胞生长因子
临床试验
受体
肾脏疾病
作者
Lipika Goyal,Funda Meric‐Bernstam,Antoine Hollebecque,Juan W. Valle,Chigusa Morizane,Thomas B. Karasic,Thomas A. Abrams,Junji Furuse,Robin K. Kelley,Philippe Cassier,Heinz‐Josef Klümpen,Heung-Moon Chang,Li-Tzong Chen,Josep Tabernero,Do‐Youn Oh,Amit Mahipal,Markus Moehler,Edith P. Mitchell,Yoshito Komatsu,Koichi Masuda,Daniel H. Ahn,Robert S. Epstein,Abdel Halim,Yao Fu,Tehseen Salimi,Volker Wacheck,Yaohua He,Mei Liu,Karim A. Benhadji,John Bridgewater
标识
DOI:10.1056/nejmoa2206834
摘要
Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors). The patients received oral futibatinib at a dose of 20 mg once daily in a continuous regimen. The primary end point was objective response (partial or complete response), as assessed by independent central review. Secondary end points included the response duration, progression-free and overall survival, safety, and patient-reported outcomes.Between April 16, 2018, and November 29, 2019, a total of 103 patients were enrolled and received futibatinib. A total of 43 of 103 patients (42%; 95% confidence interval, 32 to 52) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations. At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months. Common treatment-related grade 3 adverse events were hyperphosphatemia (in 30% of the patients), an increased aspartate aminotransferase level (in 7%), stomatitis (in 6%), and fatigue (in 6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2% of the patients. No treatment-related deaths occurred. Quality of life was maintained throughout treatment.In previously treated patients with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to measurable clinical benefit. (Funded by Taiho Oncology and Taiho Pharmaceutical; FOENIX-CCA2 ClinicalTrials.gov number, NCT02052778.).