Wagner Andrew J, Tap William D, Bauer Sebastian, Blay Jean-Yves, Desai Jayesh, Gelderblom Hans, Palmerini Emanuela, Ryan Christopher W, Peterfy Charles, Healey John H, van de Sande Michiel, Qian Meng, Shuster Dale E, Rajper Abdul, Ye Xin, Tecson Kristen, Wooddell Margaret J, Stacchiotti Silvia
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, United States.
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065, United States.
Oncologist. 2025 Jul 4;30(7). doi: 10.1093/oncolo/oyae345.
Pexidartinib is approved in the US, Taiwan, and Korea for adults with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery based on the phase III ENLIVEN study (NCT02371369). We report the final long-term efficacy and safety results from ENLIVEN.
Adults with symptomatic TGCT not eligible for surgery were enrolled and randomized to pexidartinib or placebo (part 1). The blinded phase (part 1) ended at week 25; patients received pexidartinib (800 mg/day) until progression, toxicity, or study completion (part 2). This analysis includes patients who received pexidartinib at any time during ENLIVEN. Centrally reviewed overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and tumor volume score (TVS), time to response, duration of response (DOR), patient-reported outcomes (PROs), and long-term safety were assessed.
Overall, 91 patients received pexidartinib. With a median follow-up of 31.2 (range: 2-66) months, ORR was 60.4% and 68.1% by RECIST and TVS, respectively. Median DOR by RECIST was not reached (range: 0.03-63.4 months). Most responses were within the first 6 months of treatment; most responders were on 800 mg vs 600/400 mg dose levels, respectively. Throughout parts 1 and 2, 3 (3%) patients had progressive disease per RECIST without dose reduction/interruption. PROs improved or were maintained. The most common grade 3/4 treatment-emergent adverse events were aspartate aminotransferase (AST) increase (9%), alanine aminotransferase (ALT) increase (10%), and hypertension (8%). Twenty-eight (31%) patients had AST or ALT ≥3 times the upper limit of normal (ULN); 17 (19%) patients had AST or ALT ≥5 times the ULN. No new safety signals were observed after long-term pexidartinib treatment.
Final long-term ENLIVEN results demonstrated that pexidartinib sustained clinical benefit, with increased ORR by RECIST and TVS compared to the end of the blinded phase at week 25. No new safety signals were reported.
基于III期ENLIVEN研究（NCT02371369），培西达替尼在美国、台湾和韩国被批准用于患有伴有严重发病率或功能受限且手术无法改善的症状性腱鞘巨细胞瘤（TGCT）的成人患者。我们报告了ENLIVEN研究的最终长期疗效和安全性结果。
纳入不符合手术条件的有症状TGCT成人患者，并将其随机分为培西达替尼组或安慰剂组（第1部分）。盲法阶段（第1部分）在第25周结束；患者接受培西达替尼（800毫克/天）直至病情进展、出现毒性反应或研究结束（第2部分）。该分析包括在ENLIVEN研究期间任何时间接受过培西达替尼治疗的患者。评估了根据实体瘤疗效评价标准（RECIST）v1.1进行的中心审查的总缓解率（ORR）、肿瘤体积评分（TVS）、缓解时间、缓解持续时间（DOR）、患者报告结局（PRO）以及长期安全性。
总体而言，91例患者接受了培西达替尼治疗。中位随访时间为31.2（范围：2 - 66）个月，根据RECIST和TVS评估的ORR分别为60.4%和68.1%。根据RECIST评估的中位DOR未达到（范围：0.03 - 63.4个月）。大多数缓解发生在治疗的前6个月内；大多数缓解者分别接受800毫克与600/400毫克剂量水平的治疗。在第1部分和第2部分中，根据RECIST标准，3例（3%）患者在未降低剂量/未中断治疗的情况下出现疾病进展。PRO有所改善或维持稳定。最常见的3/4级治疗中出现的不良事件为天冬氨酸转氨酶（AST）升高（9%）、丙氨酸转氨酶（ALT）升高（10%）和高血压（8%）。28例（31%）患者的AST或ALT升高至正常上限（ULN）的3倍以上；17例（19%）患者的AST或ALT升高至ULN的5倍以上。长期培西达替尼治疗后未观察到新的安全信号。
ENLIVEN研究的最终长期结果表明，培西达替尼持续具有临床益处，与第25周盲法阶段结束时相比，根据RECIST和TVS评估的ORR有所提高。未报告新的安全信号。
