Long-term efficacy and safety of pexidartinib in patients with tenosynovial giant cell tumor: final results of the ENLIVEN study
Andrew J Wagner, William D Tap, Sebastian Bauer, Jean-Yves Blay, Jayesh Desai, Hans Gelderblom, Emanuela Palmerini, Christopher W Ryan, Charles Peterfy, John H Healey, Michiel van de Sande, Meng Qian, Dale E Shuster, Abdul Rajper, Xin Ye, Kristen Tecson, Margaret J Wooddell, Silvia StacchiottiAbstract
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.