Hannover Medical School, Hannover, Germany; Toronto General Hospital, Toronto; Princess Margaret Cancer Centre, Toronto, Canada.
University of Michigan, Ann Arbor, USA.
ESMO Open. 2024 Jun;9(6):103488. doi: 10.1016/j.esmoop.2024.103488. Epub 2024 Jun 4.
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.
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.
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.
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.
成纤维细胞生长因子受体 2（FGFR2）融合和重排是胆管癌（CCA）中具有临床意义的基因组改变。培米替尼是一种选择性、有效且口服的 FGFR1-3 抑制剂，在 FIGHT-202 中（NCT02924376），用于治疗先前接受过治疗的、晚期/转移性 CCA 伴有 FGFR2 改变的患者中显示出疗效。我们报告了延长随访期间的最终结果。
多中心、开放标签、单臂、二期 FIGHT-202 研究纳入了年龄≥18 岁的、先前接受过治疗的晚期/转移性 CCA 伴有 FGFR2 融合或重排（队列 A）、其他 FGF/FGFR 改变（队列 B）或无 FGF/FGFR 改变（队列 C）的患者。患者接受培米替尼 13.5 mg 每日一次口服，21 天为一个周期（2 周用药，1 周停药），直至疾病进展或出现不可接受的毒性。主要终点是独立评审委员会按 RECIST v1.1 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）和安全性。
FIGHT-202 共纳入 147 例患者（队列 A，108 例；队列 B，20 例；队列 C，17 例；未确认的 FGF/FGFR 改变，2 例）。最终分析时，145 例（98.6%）因疾病进展（71.4%）、患者撤回（8.2%）或不良事件（AE；6.8%）而停止治疗。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%）；分别有 3 例和 37 例患者完全缓解和部分缓解。中位 DOR 为 9.1（6.0-14.5）个月；中位 PFS 和 OS 分别为 7.0（6.1-10.5）个月和 17.5（14.4-22.9）个月。最常见的治疗相关不良事件（TEAE）是高磷血症（58.5%）、脱发（49.7%）和腹泻（47.6%）。总体而言，15 例（10.2%）患者因 TEAEs 而停止使用培米替尼；最常发生的 TEAEs 是肠梗阻和急性肾损伤（各 2 例）。
在 FIGHT-202 的延长随访期间，培米替尼在先前接受过治疗的、晚期/转移性 CCA 伴有 FGFR2 改变的患者中显示出持久的缓解和延长的 OS，且 AE 可管理。
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