背景:成纤维细胞生长因子受体2(FGFR2)融合和重排是胆管癌(CCA)中临床可行的基因组改变。Pemigatinib是一种选择性的,强力,口服FGFR1-3抑制剂,并在先前治疗的患者中证明了疗效,FIGHT-202中FGFR2改变的晚期/转移性CCA(NCT02924376)。我们报告了延长随访期的最终结果。
方法:多中心,开放标签,单臂,II期FIGHT-202研究纳入了年龄≥18岁的患者,这些患者先前已治疗过FGFR2融合或重排的晚期/转移性CCA(队列A),其他FGF/FGFR改变(队列B),或无FGF/FGFR改变(队列C)。患者在21天的周期内接受每日一次口服培米加替尼13.5mg(2周,1周休息),直到疾病进展或不可接受的毒性。主要终点是由独立审查委员会根据RECISTv1.1评估的队列A的客观缓解率(ORR);次要终点包括缓解持续时间(DOR),无进展生存期(PFS),总生存期(OS),和安全。
结果:FIGHT-202招募了147名患者(队列A,108;队列B,20;队列C,17;未经证实的FGF/FGFR改变,2).最后分析,145人(98.6%)因疾病进展而停止治疗(71.4%),患者停药(8.2%),或不良事件(不良事件;6.8%)。中位随访时间为45.4个月。队列A的ORR为37.0%(95%置信区间27.9%至46.9%);在3例和37例患者中观察到完全和部分缓解,分别。中位DOR为9.1(6.0-14.5)个月;中位PFS和OS为7.0(6.1-10.5)个月和17.5(14.4-22.9)个月,分别。最常见的治疗引起的AE(TEAE)是高磷血症(58.5%),脱发(49.7%),腹泻(47.6%)。总的来说,15例(10.2%)患者出现TEAE导致pemigatinib停药;肠梗阻和急性肾损伤(各n=2)发生频率最高。
结论:在先前接受过治疗的患者中,Pemigatinib表现出持久的缓解和OS延长,AE可控,在FIGHT-202的延长随访期内,晚期/转移性CCA伴FGFR2改变。
BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period.
METHODS: The multicenter, open-label, single-arm, phase II FIGHT-202
study enrolled patients ≥18 years old with previously treated advanced/metastatic CCA with FGFR2 fusions or rearrangements (cohort A), other FGF/FGFR alterations (cohort B), or no FGF/FGFR alterations (cohort C). Patients received once-daily oral pemigatinib 13.5 mg in 21-day cycles (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) in cohort A assessed as per RECIST v1.1 by an independent review committee; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: FIGHT-202 enrolled 147 patients (cohort A, 108; cohort B, 20; cohort C, 17; unconfirmed FGF/FGFR alterations, 2). By final analysis, 145 (98.6%) had discontinued treatment due to progressive disease (71.4%), withdrawal by patient (8.2%), or adverse events (AEs; 6.8%). Median follow-up was 45.4 months. The ORR in cohort A was 37.0% (95% confidence interval 27.9% to 46.9%); complete and partial responses were observed in 3 and 37 patients, respectively. Median DOR was 9.1 (6.0-14.5) months; median PFS and OS were 7.0 (6.1-10.5) months and 17.5 (14.4-22.9) months, respectively. The most common treatment-emergent AEs (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). Overall, 15 (10.2%) patients experienced TEAEs leading to pemigatinib discontinuation; intestinal obstruction and acute kidney injury (n = 2 each) occurred most frequently.
CONCLUSIONS: Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202.