The Food and Drug Administration (FDA) approved pexidartinib for the treatment of adults with symptomatic tenosynovial giant cell tumor (TGCT).
The Food and Drug Administration (FDA) approved pexidartinib (Turalio) for the treatment of adults with symptomatic tenosynovial giant cell tumor (TGCT), according to the agency.
The drug works by inhibiting the colony-stimulating factor 1 receptor (CSF1R), and its approval is coming after the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12 to 3 in favor of the indication back in May 2019. Pexidartinib was also granted a priority review in February 2019 based on findings from the international phase III ENLIVEN study.
“While nodular giant cell tumors of tendon and sheath can most often be treated successfully with surgery, diffuse type can be quite recalcitrant to treatment, and surgery in these cases tend to be associated with worse functional outcomes and/or severe morbidity,” said Valerae Lewis, MD, chair of orthopaedic oncology at The University of Texas MD Anderson Cancer Center, in an interview with Oncology Nursing News.
ENLIVEN was a multicenter, double-blind study that compared pexidartinib versus placebo in patients with symptomatic, advanced TGCT. To qualify for the study’s enrollment, patients had to face potential worsening of functional limitation or severe morbidity if their tumor was removed. They also had to have histologically confirmed, advanced, and symptomatic TGCT with measurable disease that was 2 cm or larger, according to RECIST v1.1 criteria.
Study participants were enrolled 1:1 to receive either pexidartinib or placebo at a dosage of 1,000 mg a day for 2 weeks, and then 800 mg a day for 22 weeks. The primary endpoint of the study was overall response rate (ORR) after 25 weeks.
Findings showed that those given pexidartinib had an ORR of 38%, compared to no responses in those who were given placebo. The complete response rate was 15%, and the partial response rate was 23%.
The approval could generate excitement for individuals with the rare disease, as TGCT, a nonmalignant tumor of the joint or tendon sheath, can be debilitating. It is often associated with severe morbidity and functional limitations. The disease is mainly treated with surgery.
“A non-surgical treatment option for these patients is a wonderful opportunity,” Lewis said. “Improvement in range of motion, PROMIS physical function, and decreased stiffness of the involved joint have been noted. For these patients to regain function and quality of life is extraordinary.”
However, Lewis did mention that patients on this treated must be closely monitored by healthcare providers for adverse events.
“While several minor side effects have been observed, hepatic toxicities can be the most severe. Caregivers should pay close attention to elevation of LFTs and symptoms of liver toxicities,” she said.
Additionally, the drug comes with a Boxed Warning label regarding the risk of serious and potentially fatal liver injury. Common adverse events (AEs) included: increased lactate dehydrogenase, increased aspartate aminotransferase, loss of hair color, increased alanine aminotransferase and increased cholesterol. Additional AEs included neutropenia, increased alkaline phosphatase, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia and decreased phosphate.
“TGCT can cause debilitating symptoms for patients such as pain, stiffness and limitation of movement. The tumor can significantly affect a patient’s quality of life and cause severe disability,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. in a statement. “Surgery is the primary treatment option, but some patients are not eligible for surgery, and tumors can recur, even after the procedure. Today’s approval is the first FDA-approved therapy to treat this rare disease.”