Rugo Hope S, Campbell Mike, Yau Christina, Jo Chien A, Wallace Anne M, Isaacs Claudine, Boughey Judy C, Han Hyo S, Buxton Meredith, Clennell Julia L, Asare Smita M, Steeg Katherine, Wilson Amy, Singhrao Ruby, Matthews Jeffrey B, Perlmutter Jane, Fraser Symmans W, Hylton Nola M, DeMichele Angela M, Yee Douglas, Van't Veer Laura J, Berry Donald A, Esserman Laura J
University of California San Francisco, Box 1710, San Francisco, CA, 94143, USA.
University of California San Diego, San Diego, CA, USA.
Breast Cancer Res Treat. 2025 Feb;209(3):487-492. doi: 10.1007/s10549-024-07555-9. Epub 2024 Dec 3.
We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.
I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status. The study endpoint is pathologic complete response.
A total of 9 participants were randomized to receive pexidartinib with neoadjuvant paclitaxel before enrollment was halted due to a serious adverse event of vanishing bile duct syndrome. No participants received a full course of the study drug.
Although there remains interest in agents targeting CSF-1, hepatic toxicity appears to be a limiting factor for their use in early breast cancer.
NCT01042379 ( www.
gov/ct2/show/NCT01042379 ).
我们在I-SPY2平台试验中研究了集落刺激因子-1受体小分子受体酪氨酸激酶抑制剂培西达替尼在II/III期乳腺癌中的作用。
I-SPY2是一项适应性平台试验，其特点是在紫杉醇和阿霉素/环磷酰胺标准新辅助治疗的背景下，设置多个使用实验药物的治疗组，随后进行确定性手术。适应性随机化引擎根据每种药物在特定乳腺癌亚型（基于激素受体和HER2受体状态）中的累积表现，优先分配患者。研究终点是病理完全缓解。
共有9名参与者被随机分配接受培西达替尼与新辅助紫杉醇治疗，但由于出现胆管消失综合征这一严重不良事件，在入组停止前，没有参与者接受完整疗程的研究药物。
尽管对靶向CSF-1的药物仍有兴趣，但肝毒性似乎是其在早期乳腺癌中应用的限制因素。
NCT01042379（www.CLINICALTRIALS.gov/ct2/show/NCT01042379）
