On August 2, 2019, the FDA approved pexidartinib (Turalio; Daiichi Sankyo) capsules, a kinase inhibitor, for adults with symptomatic tenosynovial giant-cell tumor (TGCT), which is associated with severe morbidity or functional limitations, who are not candidates for surgery. Pexidartinib is the first systemic therapy approved for patients with TGCT. The FDA granted pexidartinib a priority review and breakthrough therapy and orphan drug designations.
The FDA approval was based on the international, multicenter, randomized (1:1), double-blind, placebo-controlled clinical trial of 120 patients with TGCT that could not be removed by surgery. The primary end point was durable overall response rate (ORR), as determined by an independent review committee at week 25.
Patients were randomized in a 1:1 ratio to pexidartinib or to placebo. After 25 weeks, the ORR was 38% (95% confidence interval, 27-50), including 15% complete responses and 23% partial responses, with pexidartinib versus no responses with placebo (P <.0001). Overall, 22 patients who responded to pexidartinib therapy maintained the response for ≥6 months. In addition, 13 patients maintained the response for ≥12 months.
Patients with enough data had significant improvement in the range of motion of the affected joint at week 25 with pexidartinib versus placebo.
The most common side effects with pexidartinib were increased lactate dehydrogenase, increased aspartate aminotransferase, hair color changes, increased alanine aminotransferase, and increased cholesterol. Pexidartinib was approved with a boxed warning about the risk for fatal liver injury; the drug is only available through a Risk Evaluation and Mitigation Strategy program.