Pexidartinib Elicits Sustained Benefit in Tenosynovial Giant Cell Tumors

"The final results of the ENLIVEN trial show the potential for long-term tumor responses with [pexidartinib] treatment with a safety profile consistent with earlier findings," according to study author Andrew J. Wagner, MD, PhD.

Pexidartinib (Turalio) yielded sustained clinical benefits, with improvements in overall response rates (ORRs), among patients with tenosynovial giant cell tumors (TGCTs) not amenable to surgery, according to the final results from the phase 3 ENLIVEN trial (NCT02371369) published in The Oncologist.1

After a median follow-up of 31.2 months (range, 2-66), data showed an ORR of 60% per RECIST criteria; no differences in ORRs existed between patients who were assigned to receive pexidartinib in part 1 (61%) vs those who received the agent in part 2 only (60%). Per tumor volume score (TVS), the ORR was 68%, with no differences in ORRs for patients who received pexidartinib in part 1 (67%) and those in the crossover group (70%).

Based on RECIST criteria, the median time to response was 5.1 months (range, 2-53), and 66% of patients achieved a response within the first 6 months of therapy. Data showed that the median duration of response (DOR) was not reached (NR; range, 0.03-63.4) per RECIST criteria and NR (range, 0.03-63.5) per TVS.

“Prior to the approval of [pexidartinib], the first FDA-approved systemic therapy for TGCT, there were limited treatment options beyond additional surgery,” lead study author Andrew J. Wagner, MD, PhD, a medical oncologist from Dana-Farber Cancer Institute and Harvard Medical School, stated in a press release on these findings.2 “The final results of the ENLIVEN trial show the potential for long-term tumor responses with [pexidartinib] treatment with a safety profile consistent with earlier findings.”

The FDA previously approved pexidartinib for patients with symptomatic TGCTs related to severe morbidity or functional limitations that are not amenable to surgery in August 2019, based on data from the ENLIVEN trial.3

In the first part of the double-blind phase 3 ENLIVEN trial, 121 patients were randomly assigned 1:1 to receive pexidartinib at 1000 mg per day for 2 weeks, followed by 800 mg per day for 22 weeks or matched placebo. In part 2 of the trial, patients crossed over from placebo to pexidartinib at 800 mg split twice a day or the dose they started with in part 1 and continued treatment until progressive disease, toxicity, or study completion.

The trial’s primary end point was ORR per RECIST v1.1 guidelines. Secondary end points included mean change from baseline in the range of affected joint motion, responses per TVS, mean change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)−Physical Function scale, and mean change from baseline in worst stiffness.

Those with histologically confirmed, advanced, symptomatic TGCT with measurable tumors of 2 cm or more for which surgical resection could confer worsening of functional limitation or severe morbidity were eligible for enrollment on the trial.

Among 91 patients who received pexidartinib, the median age was 46.0 years (range, 20-79), and most patients were female (56%) and White (90%). A majority of the population had diffuse TGCT (87%) and tumors located in the lower body (90%), especially the knees (58%). The median time from diagnosis to randomization was 1251 days (range, 15-14,912).

Overall, 52% (n = 32/61) and 53% (n = 31/59) of those randomly assigned to the pexidartinib and placebo arms, respectively, underwent prior surgery for TGCT at a median of 2 previous procedures. Additionally, 3 patients randomly assigned to the investigational agent received subsequent surgery.

Patient-reported outcome data revealed that pexidartinib, on average, sustained improvements in range of motion, worst stiffness, Brief Pain Inventory worse pain, and PROMIS-Physical Function at week 25 throughout part 2 of the trial.

The most common any-grade adverse effects included hair color changes (75.8%), fatigue (47.3%), nausea (38.5%), and increased aspartate aminotransferase (37.4%). The most common grade 3/4 toxicities included increased alanine aminotransferase (9.9%), increased aspartate aminotransferase (8.8%), and hypertension (7.7%).

“The final results of ENLIVEN contribute to the body of evidence supporting the long-term benefit of [pexidartinib]….Since its approval nearly 6 years ago, more than 750 patients in the US have been treated with [pexidartinib], and we remain committed to working closely with healthcare professionals to help identify appropriate patients who may benefit from this treatment,” Patricia Judson, MD, vice president of US Medical Affairs at Daiichi Sankyo, the developer of pexidartinib, concluded in the press release.2

References

1. Wagner AJ, Tap WD, Bauer S, et al. Long-term efficacy and safety of pexidartinib in patients with tenosynovial giant cell tumor: final results of the ENLIVEN study. Oncologist. 2025;30(7):oyae345. doi:10.1093/oncolo/oyae345.
2. TURALIO® final long-term data showed sustained clinical benefit in patients with tenosynovial giant cell tumor from open-label extension of ENLIVEN phase 3 trial. News release. Daiichi-Sankyo. July 9, 2025. Accessed July 10, 2025. https://tinyurl.com/2e7awksp
3. FDA approves pexidartinib for tenosynovial giant cell tumor. News release. FDA. August 2, 2019. Accessed July 10, 2025. https://tinyurl.com/mra9bu7y