Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
BMC Cancer. 2024 Aug 13;24(1):1006. doi: 10.1186/s12885-024-12584-0.
FGFR genomic aberrations occur in approximately 5-10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer.
Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics.
Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7-63.6); the median progression-free survival was 5.6 months (95% CI, 3.6-12.7) and median overall survival was 40.2 months (95% CI, 12.4-not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5-57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%).
Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals.
This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.
FGFR 基因组异常发生在大约 5-10%的人类癌症中。厄达替尼先前在 FGFR 改变的晚期实体瘤（如脑胶质瘤、胸、胃肠道、妇科和其他罕见癌症）中显示出疗效和安全性。然而，其在亚洲患者中的疗效和安全性在很大程度上仍不清楚。我们进行了一项多中心、开放标签、单臂 2a 期研究，评估厄达替尼在亚洲 FGFR 改变的晚期胆管癌、非小细胞肺癌（NSCLC）和食管癌患者中的疗效。
经病理/细胞学证实的晚期或难治性肿瘤患者，符合分子和研究入选标准，接受口服厄达替尼 8mg，每日一次，在 28 天周期中可选择进行药效学指导的加量至 9mg，除了 4 名 NSCLC 患者，他们接受厄达替尼 10mg（7 天 ON/7 天 OFF），因为他们是在方案修订前招募的。主要终点为研究者评估的根据 RECIST v1.1 标准的客观缓解率。次要终点包括无进展生存期、缓解持续时间、疾病控制率、总生存期、安全性和药代动力学。
35 名患者（胆管癌：22 名；NSCLC：12 名；食管癌：1 名）入选。截至数据截止日期（2021 年 11 月 19 日），胆管癌患者的客观缓解率为 40.9%（95%CI，20.7-63.6）；中位无进展生存期为 5.6 个月（95%CI，3.6-12.7），中位总生存期为 40.2 个月（95%CI，12.4-不可估计）。无 RET/FGFR 改变的 NSCLC 患者达到客观缓解，疾病控制率为 25.0%（95%CI，5.5-57.2%），3 名患者病情稳定。唯一一名患有食管癌的患者获得部分缓解。所有患者均出现治疗相关不良事件，22 名（62.9%）患者出现 3 级及以上治疗相关不良事件。高磷血症是最常见的治疗相关不良事件（所有级别，85.7%）。
厄达替尼在选定的晚期实体瘤中，特别是在晚期 FGFR 改变的胆管癌患者中，显示出疗效。治疗是可耐受的，没有新的安全性信号。
该试验在 ClinicalTrials.gov 注册（NCT02699606）；研究注册（首次发布）：2016 年 4 月 3 日。
