On August 2, 2019, the Food and Drug Administration approved pexidartinib (TURALIO™, Daiichi Sankyo) capsules for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Pexidartinib is the first systemic therapy approved for patients with TGCT.
The approval was based on durable overall response rate (ORR) observed in an international, multicenter, randomized (1:1), double-blind, placebo-controlled trial enrolling 120 patients with TGCT not amenable to surgical resection (ENLIVEN, NCT02371369). ORR was determined by an independent review committee at week 25 (Response Evaluation Criteria in Solid Tumors 1.1). After 25 weeks of treatment, the ORR was 38% (95% confidence interval: 27, 50), with a 15% complete response rate and a 23% partial response rate. No patients receiving placebo had a response (p<0.0001). Twenty-two of 23 patients who responded and had been followed for a minimum of 6 months after the initial response maintained the response for ≥6 months. In addition, 13 of 13 patients who responded and had been followed for a minimum of 12 months after the initial response maintained the response for ≥12 months.
Range of motion, measured as a percent of normal, was assessed for each affected joint using a goniometer. In patients who had sufficient data to permit analysis, a statistically significant improvement from baseline in range of motion of the affected joint at week 25 was observed in patients who received pexidartinib compared to those receiving placebo.
Common side effects of pexidartinib were increased lactate dehydrogenase, increased aspartate aminotransferase, hair color changes, increased alanine aminotransferase, and increased cholesterol. Additional side effects included neutropenia, increased alkaline phosphatase, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate.
The prescribing information includes a Boxed Warning advising health care professionals and patients about the risk of serious and potentially fatal liver injury. Health care professionals should monitor liver tests prior to initiating pexidartinib and weekly for the first 8 weeks, then every 2 weeks for the next month, and, thereafter, every 3 months. In patients experiencing liver injury, the pexidartinib dose should be reduced or discontinued based on severity of the injury. Pexidartinib is available only through a Risk Evaluation and Mitigation Strategy Program.
The recommended pexidartinib dose is 400 mg (2 capsules) orally twice daily on an empty stomach.
FDA granted pexidartinib breakthrough therapy and orphan drug designation, and granted this application priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
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