Phase III Trial: Pexidartinib Improves Outcomes for Patients With Rare Joint Tumor

The U.S. Food and Drug Administration recently approved pexidartinib (Turalio™) for the treatment of advanced tenosynovial giant cell tumor (TGCT). The phase III ENLIVEN trial for which the approval was based found that this is the first systemic therapy to show a robust tumor response in TGCT with improved patient symptoms and functional outcomes. The study results were published in The Lancet.

This randomized phase III trial had two parts: Part one was a double-blind study in which patients with symptomatic, advanced TGCT for whom surgery was not recommended were randomized 1:1 to receive pexidartinib 1,000 mg pexidartinib per day orally for the first two weeks followed by 800 mg per day for 22 weeks (n=61) or placebo (n=59). Part two was an open-label study of all patients who received pexidartinib.

Pexidartinib improves response compared with placebo

Eleven patients in the placebo group and nine in the pexidartinib arm dropped out of the study. The overall response rate was 38% in the pexidartinib group (n=24) versus 0% in the placebo group after 25 weeks (95% CI, 27-53; P<0.0001). With pexidartinib, the complete response rate was 15% and the partial response rate was 23%. Twenty-two of 23 responders who were followed for a minimum of six months after initial response maintained their response for six or more months. All 13 responders who were followed for a minimum of 12 months after initial response maintained their response for 12 or more months.

Serious adverse events (AEs) occurred in eight (13%) patients in the pexidartinib group and one (2%) patient in the placebo group. Common AEs associated with pexidartinib were hair color changes (67%), fatigue (54%), aspartate aminotransferase increase (39%), nausea (38%), alanine aminotransferase increase (28%), and dysgeusia (25%). Three patients who received pexidartinib had aminotransferase elevations three or more times the upper limit of normal (ULN) with total bilirubin and alkaline phosphatase two or more times the ULN indicative of mixed or cholestatic hepatotoxicity; one of these lasted seven months and was confirmed by biopsy.

“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,” the researchers concluded.

Pexidartinib carries a Boxed Warning for the risk of serious and potentially fatal liver injury. Healthcare professionals should monitor liver tests prior to beginning treatment and at specified intervals during treatment.