FDA Approves First Treatment for Symptomatic Tenosynovial Giant Cell Tumor

The FDA has given the nod to pexidartinib (Turalio), marking the first approved treatment for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) with severe morbidity or functional limitations who are not responsive to improvement with surgery.

TGCT is a rare, nonmalignant tumor that affects the thin layer of tissue that covers the surfaces of joint spaces and the layer of membrane that covers tendons. TGCT causes these layers to thicken and overgrow, resulting in damage to surrounding tissue. Also referred to as pigmented villondular synovitis, the tumor can be locally aggressive and debilitating.

“The FDA approval of TURALIO represents a paradigm shift in the treatment of carefully selected TGCT patients who face significant disease morbidity and for whom surgery is not an option,” said William D. Tap, MD, chief of the Sarcoma Medical Oncology Service at Memorial Sloan Kettering Cancer Center, in a statement. “We now have a new oral treatment option that can have a meaningful clinical benefit in select patients, including a reduction in tumor size.”

The approval of Daiichi Sankyo’s pexidartinib follows positive results from the phase 3 ENLIVEN study, the first placebo-controlled study of a systemic therapy in patients with TGCT. The trial of 120 patients included 61 who received treatment with pexidartinib. The tumor response rate among patients receiving the treatment was 38% at 25 weeks, compared with 0% for patients receiving placebo. Among patients receiving pexidartinib, 15% achieved a complete response rate and 23% achieved a partial response rate.

Twenty-two of the 23 patients who responded and were followed for at least 6 months maintained their response for 6 months or longer, and all 13 responders who were followed for at least 12 months maintained their response for 12 months or longer.

The treatment comes with a boxed warning advising providers and patients about the risk of serious and potentially fatal liver injury. According to the FDA, providers should monitor liver tests prior to beginning treatment and at specified intervals throughout treatment.

Common adverse effects associated with the treatment include increased lactate dehydrogenase, increased aspartate aminotransferase, loss of hair color, increased alanine aminotransferase, and increased cholesterol. Other potential adverse effects include neutropenia, increased alkaline phosphatase, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate.

The FDA is also advising providers to warn females of reproductive age and males with a female partner to use effective contraception during treatment with pexidartinib and that women who are pregnant or breastfeeding should not take pexidartinib because it could cause harm to a developing fetus or newborn baby.