背景:FGFR基因组畸变发生在大约5-10%的人类癌症中。Erdafitinib先前已证明其在FGFR改变的晚期实体瘤中的疗效和安全性。比如神经胶质瘤,胸廓,胃肠,妇科,和其他罕见的癌症。然而,其在亚洲患者中的疗效和安全性尚不清楚.我们进行了一个多中心,开放标签,erdafitinib单臂IIa期研究评估其在FGFR改变的晚期胆管癌亚洲患者中的疗效,非小细胞肺癌(NSCLC),还有食道癌.
方法:经病理/细胞学证实的患者,先进,或符合分子和研究资格标准的难治性肿瘤患者接受口服erdafitinib8mg,每天一次,并选择在28天的周期内进行药效学指导上调至9mg,除了4例NSCLC患者在方案修订前招募时接受了erdafitinib10mg(7天开始/7天休息).主要终点是研究者根据RECISTv1.1评估的客观反应率。次要终点包括无进展生存期,响应的持续时间,疾病控制率,总生存率,安全,和药代动力学。
结果:纳入35例患者(胆管癌:22;NSCLC:12;食管癌:1)。在数据截止时(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).RET/FGFR改变的非小细胞肺癌患者无客观反应,疾病控制率为25.0%(95%CI,5.5-57.2%),3名病情稳定的患者。单个食管癌患者获得了部分缓解。所有患者都经历了因治疗引起的不良事件,22例(62.9%)患者报告了≥3级治疗引起的不良事件.高磷酸盐血症是最常见的因治疗引起的不良事件(所有级别,85.7%)。
结论:Erdafitinib在选定的晚期实体瘤的亚洲患者中证明了疗效,尤其是晚期FGFR改变的胆管癌患者。治疗是可以耐受的,没有新的安全信号。
背景:该试验已在ClinicalTrials.gov(NCT02699606)注册;研究注册(首次发布):2016年04月03日。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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%).
CONCLUSIONS: 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.
BACKGROUND: This
trial is registered with ClinicalTrials.gov (NCT02699606);
study registration (first posted): 04/03/2016.