Long-term efficacy and safety of pexidartinib in patients with tenosynovial giant cell tumor: final results of the ENLIVEN study

Wagner, AJ; Tap, WD; Bauer, S; Blay, JY; Desai, J; Gelderblom, H; Palmerini, E; Ryan, CW; Peterfy, C; Healey, JH; van de Sande, M; Qian, M; Shuster, DE; Rajper, A; Ye, X; Tecson, K; Wooddell, MJ; Stacchiotti, S

Author(s): Wagner, AJ; Tap, WD; Bauer, S; Blay, JY; Desai, J; Gelderblom, H; Palmerini, E; Ryan, CW; Peterfy, C; Healey, JH; van de Sande, M; Qian, M; Shuster, DE; Rajper, A; Ye, X; Tecson, K; Wooddell, MJ; Stacchiotti, S;
Details: Publication Year 2025-07-04,Volume 30,Issue #7,Page oyae345
Journal Title: Oncologist
Publication Type: Research article
Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Publisher: Oxford University Press
Keywords: Humans; Male; Female; Middle Aged; *Giant Cell Tumor of Tendon Sheath/drug therapy/pathology; Adult; *Aminopyridines/therapeutic use/adverse effects/pharmacology; *Pyrroles/therapeutic use/adverse effects/pharmacology/administration & dosage; Aged; Treatment Outcome; Response Evaluation Criteria in Solid Tumors; clinical trial; giant cell tumor of tendon sheath; patient-reported outcome measures; phase III
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1093/oncolo/oyae345
Open Access at Publisher's Site: https://doi.org/10.1093/oncolo/oyae345
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-08-14 05:00:30

Last Modified: 2025-08-14 05:01:06