Leiden University Medical Center, Leiden, the Netherlands.
Dana-Farber Cancer Institute, Boston, Massachusetts.
Cancer. 2021 Mar 15;127(6):884-893. doi: 10.1002/cncr.33312. Epub 2020 Nov 16.
The objective of this study was to report on the long-term effects of pexidartinib on tenosynovial giant cell tumor (TGCT).
This was a pooled analysis encompassing 3 pexidartinib-treated TGCT cohorts: 1) a phase 1 extension study (NCT01004861; 1000 mg/d; n = 39), 2) ENLIVEN patients randomized to pexidartinib (1000 mg/d for 2 weeks and then 800 mg/d; n = 61), and 3) ENLIVEN crossover patients (NCT02371369; 800 mg/d; n = 30). Eligible patients were 18 years old or older and had a histologically confirmed TGCT that was unresectable and symptomatic. Efficacy endpoints included the best overall response (complete or partial response) and the duration of response (DOR) by the Response Evaluation Criteria in Solid Tumors (RECIST) and the tumor volume score (TVS). The safety assessment included the frequency of treatment-emergent adverse events (TEAEs) and hepatic laboratory abnormalities (aminotransferase elevations and mixed/cholestatic hepatotoxicity). The data cutoff was May 31, 2019.
One hundred thirty patients with TGCT received pexidartinib (median treatment duration, 19 months; range, 1 to 76+ months); 54 (42%) remained on treatment at the end of the analysis (26 months after initial data cut of March 2017). The RECIST overall response rate (ORR) was 60%; the TVS ORR was 65%. The median times to response were 3.4 (RECIST) and 2.8 months (TVS), with 48 of the responding patients (62%) achieving a RECIST partial response by 6 months and with 72 (92%) doing so by 18 months. The median DOR was reached for TVS (46.8 months). Reported TEAEs were mostly low-grade, with hair color changes being most frequent (75%). Most liver abnormalities (92%) were aminotransferase elevations; 4 patients (3%) experienced mixed/cholestatic hepatotoxicity (all within the first 2 months of treatment), which was reversible in all cases (recovery spanned 1-7 months).
This study demonstrates the prolonged efficacy and tolerability of long-term pexidartinib treatment for TGCT.
本研究旨在报告培昔替尼治疗腱鞘巨细胞瘤（TGCT）的长期疗效。
这是一项培昔替尼治疗 TGCT 的 3 个队列的汇总分析：1）一项 1 期扩展研究（NCT01004861；1000mg/d；n=39）；2）ENLIVEN 患者随机分配至培昔替尼（1000mg/d，持续 2 周，然后 800mg/d；n=61）；3）ENLIVEN 交叉患者（NCT02371369；800mg/d；n=30）。入组患者年龄≥18 岁，且经组织学证实的 TGCT 不可切除且有症状。疗效终点包括根据实体瘤反应评估标准（RECIST）和肿瘤体积评分（TVS）评估的最佳总体缓解（完全或部分缓解）和缓解持续时间（DOR）。安全性评估包括治疗后出现的不良事件（TEAE）和肝实验室异常（转氨酶升高和混合/胆汁淤积性肝毒性）的频率。数据截止日期为 2019 年 5 月 31 日。
130 例 TGCT 患者接受了培昔替尼治疗（中位治疗时间为 19 个月；范围为 1 至 76+个月）；54 例（42%）在分析结束时（2017 年 3 月初始数据截止后 26 个月）仍在接受治疗。RECIST 总体缓解率（ORR）为 60%；TVS ORR 为 65%。反应的中位时间分别为 3.4 个月（RECIST）和 2.8 个月（TVS），48 例应答患者（62%）在 6 个月时达到 RECIST 部分缓解，72 例（92%）在 18 个月时达到该缓解。TVS 达到中位 DOR。报告的 TEAEs 大多为低级别，头发颜色改变最常见（75%）。大多数肝异常（92%）为转氨酶升高；4 例（3%）发生混合/胆汁淤积性肝毒性（均在治疗的前 2 个月内），所有病例均为可逆（恢复时间为 1-7 个月）。
本研究表明，长期使用培昔替尼治疗 TGCT 可延长疗效和耐受性。
