William D. Tap is Chief Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer Center. An expert with soft tissue and bone sarcomas as well as oncology-focused drug development, he leads multidisciplinary teams of physician-scientists, nurses, and patient support advocates who care for individuals with sarcoma.

Recently, he served as Principal Investigator for the pivotal phase 3 ENLIVEN, leading to its FDA Approval.

The study led to the approval of the drug. This success of this study has led to the Food and Drug Administration (FDA) approval of Daiichi Sankyo’s TURALIO™ (pexidartinib), the only approved therapy for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.

As noted in a recent Daiichi Sankyo press release, Dr. Tap noted “We now have a new oral treatment option that can have a meaningful clinical benefit in select patients, including a reduction in tumor size.”

What is symptomatic tenosynovial giant cell tumor (TGCT)?

A rare tumor which can impact patients differently. Known as TGCT, they are often cured with surgery if possible. Also referred to as PVNS or GCT-TS, these rare, non-malignant tumors can be locally aggressive. TGCT affects the synovium-lined joints, bursae and tendon sheaths, resulting in reduced mobility in the affected joint or limb.

The cause is not known and the estimated incidence of TGCT is 11 to 50 cases per million person-years, based on studies in three countries, reports the Daiichi Sankyo press release. TGCT is subcategorized into two types including 1) localized, which is more common and accounts for 80% to 90% of cases and 2) diffuse, which accounts for 10% to 20% of cases.

TURALIO Approval comes with Boxed Warning

The FDA approval comes with Boxed Warning for hepatotoxicity due to the risk of serious and potentially fatal liver injury. Out of 768 patients who received TURALIO in clinical trials, there were two irreversible cases of cholestatic liver injury. One patient died with advanced cancer and ongoing liver toxicity and one patient required a liver transplant.


Known as pexidartinib, TURALIO is an oral small molecule that inhibits CSF 1R (colony stimulating factor-1 receptor), which is a primary growth driver of abnormal cells in the synovium that cause TGCT. The drug inhibits KIT and FLT3-ITD. TURALIO was discovered by Plexxikon Inc., the small molecule structure-guided R&D center of Daiichi Sankyo.

ASCO Recognition

The American Society of Clinical Oncology (ASCO) recognized “Progress in Treating Rare Cancers” as the “Advance of the Year” and selected pexidartinib as one of five significant advancements in rare disease treatment, calling it the first promising investigational therapy for TGCT. Consequently, TURALIO was granted Priority Review, Breakthrough Therapy designation and Orphan Drug status by the FDA. It is currently under review by the European Medicines Agency and has received Orphan Designation there.

Source: Memorial Sloan Kettering Cancer Center

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