Pexidartinib Improves Overall Response in Patients with TGCT

Findings from the phase 3 ENLIVEN trial suggest pexidartinib as a potential treatment option for tenosynovial giant cell tumor (TGCT) in patients not amenable to surgical resection (Lancet. 2019 Aug 10. Epub 2019 Jun 19).

There is currently no systemic therapy approved for use after surgery for TGCT.

“We aimed to evaluate pexidartinib, a CSF1 receptor inhibitor, in patients with TGCT to provide them with a viable systemic treatment option, especially in cases that are not amenable to surgical resection,“ explained William D. Tap, MD, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, and colleagues when discussing the importance of the research.

A total of 174 patients with symptomatic, advanced TGCT were considered for eligibility from May 2015 to September 2016. Ultimately, 120 patients were enrolled in the phase 3 study and randomly assigned to the pexidartinib arm (n = 61) or placebo arm (n = 59).

Treatment with pexidartinib consisted of 1000 mg pexidartinib daily for the first 2 weeks, followed by 800 mg daily for 22 weeks.

The primary end point was overall response at week 25, assessed via RECIST, version 1.1. In addition, safety of all patients who received at least 1 dose of pexidartinib was analyzed.

The overall response rate was achieved by 24 (39%) patients in the pexidartinib arm versus 0 patients in the placebo arm.

In the pexidartinib arm, 13% of patients experienced serious adverse events (AEs) versus 2% in the placebo arm. The most common pexidartinib-related AEs were changes in hair color (67%), fatigue (54%), aspartate aminotransferase increase (39%), and nausea (38%).  Mixed or cholestatic hepatotoxicity was identified as a risk because of aminotransferase and alkaline phosphatase elevations >2 times the normal level documented in 3 patients in the pexidartinib arm.

“Pexidartinib is the first systemic therapy to show a robust tumour response in TGCT with improved patient symptoms and functional outcomes,” Dr Tap et al concluded.

“Pexidartinib could be considered as a potential treatment for TGCT associated with severe morbidity or functional limitations in cases not amenable to improvement with surgery,” they added.—Kaitlyn Manasterski