Long-term efficacy and safety of pexidartinib in patients with tenosynovial giant cell tumor: Final results of the ENLIVEN study Journal Article
| Authors: | Wagner, A. J.; Tap, W. D.; Bauer, S.; Blay, J. Y.; Desai, J.; Gelderblom, H.; Palmerini, E.; Ryan, C. W.; Peterfy, C.; Healey, J. H.; Van De Sande, M.; Qian, M.; Shuster, D. E.; Rajper, A.; Ye, X.; Tecson, K.; Wooddell, M. J.; Stacchiotti, S. |
| Article Title: | Long-term efficacy and safety of pexidartinib in patients with tenosynovial giant cell tumor: Final results of the ENLIVEN study |
| 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. © 2025 The Author(s). Published by Oxford University Press. |
| Keywords: | adult; controlled study; treatment outcome; treatment response; aged; middle aged; major clinical study; clinical trial; fatigue; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; nuclear magnetic resonance imaging; follow up; liver toxicity; skin defect; tumor volume; randomized controlled trial; pathology; arthralgia; pruritus; rash; alanine aminotransferase; aspartate aminotransferase; multicenter study; nausea and vomiting; drug toxicity; headache; phase 3 clinical trial; drug therapy; periorbital edema; pyrroles; crossover procedure; giant cell; disease exacerbation; pyrrole derivative; dysgeusia; patient-reported outcome measures; tendon sheath; hypertransaminasemia; phase iii; long term exposure; patient-reported outcome; response evaluation criteria in solid tumors; humans; human; male; female; article; aminopyridines; aminopyridine derivative; pexidartinib; giant cell tumor of tendon sheath |
| Journal Title: | The Oncologist |
| Volume: | 30 |
| Issue: | 7 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2025-07-01 |
| Start Page: | oyae345 |
| Language: | English |
| DOI: | 10.1093/oncolo/oyae345 |
| PUBMED: | 40613752 |
| PROVIDER: | scopus |
| PMCID: | PMC12231594 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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