Wheless Margaret C, Zemla Tyler J, Hubbard Joleen M, Strickler John H, Gbolahan Olumide B, Wilson Luke, Waechter Blake, Ou Fang-Shu, Nixon Andrew B, Bekaii-Saab Tanios S, Ciombor Kristen K
Department of Internal Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, United States.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States.
Oncologist. 2025 Jun 4;30(6). doi: 10.1093/oncolo/oyaf069.
FGFR alterations are known to be driver alterations in several tumor types. We aimed to assess the efficacy of pemigatinib, an oral FGFR1-3 inhibitor, in patients with metastatic or unresectable colorectal cancer whose tumors harbored FGF/FGFR alterations.
The ACCRU-GI-1701 is a single-arm phase II trial which enrolled patients with previously treated FGF/FGFR-altered metastatic colorectal cancer to receive oral pemigatinib daily in 21-day cycles. The primary endpoint is objective response. Secondary endpoints include clinical benefit, progression-free survival, overall survival, quality of life, and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04096417).
Of the 14 patients included in the interim analysis, the objective response rate as well as clinical benefit rate were 0%. Given these results, the trial closed to enrollment after stage one due to futility. A total of 42.9% of patients had at least one grade 3 or higher AE, the most common being anemia and fatigue.
Pemigatinib monotherapy did not lead to objective responses in patients with chemorefractory metastatic colorectal cancer harboring FGF/FGFR alterations, although it was overall relatively well tolerated with no new safety signals. Notably, 93% (n = 13) of patients had only FGF/FGFR mutations and amplifications; one patient had an FGFR3-WHSC1 fusion at a low cfDNA percentage (0.02%).
已知FGFR改变是多种肿瘤类型的驱动性改变。我们旨在评估口服FGFR1-3抑制剂培米替尼对肿瘤存在FGF/FGFR改变的转移性或不可切除结直肠癌患者的疗效。
ACCRU-GI-1701是一项单臂II期试验，纳入先前接受过治疗、FGF/FGFR改变的转移性结直肠癌患者，接受培米替尼口服，每日一次，每21天为一个周期。主要终点是客观缓解。次要终点包括临床获益、无进展生存期、总生存期、生活质量和不良事件（AE）。该试验已在ClinicalTrials.gov注册（NCT04096417）。
在中期分析纳入的14例患者中，客观缓解率和临床获益率均为0%。鉴于这些结果，该试验在第一阶段后因无效而停止入组。共有42.9%的患者发生至少1次3级或更高等级AE，最常见的是贫血和疲劳。
培米替尼单药治疗对存在FGF/FGFR改变的化疗难治性转移性结直肠癌患者未产生客观缓解，尽管总体耐受性相对良好，未发现新的安全信号。值得注意的是，93%（n = 13）的患者仅存在FGF/FGFR突变和扩增；1例患者在cfDNA低比例（0.02%）时存在FGFR3-WHSC1融合。
