NCCN Publishes Guidelines Listing Pexidartinib as Category 1 Recommended Therapy in TGCT

The National Comprehensive Cancer Network recently published updated Clinical Practice Guidelines in Oncology for Soft Tissue Sarcoma, listing pexidartinib as a systemic treatment for patients with tenosynovial giant cell tumor.

The National Comprehensive Cancer Network (NCCN) recently published updated Clinical Practice Guidelines in Oncology for Soft Tissue Sarcoma, listing pexidartinib (Turalio) as a systemic treatment for patients with tenosynovial giant cell tumor (TGCT).1

The NCCN updated its clinical guidelines in August 2019 to include pexidartinib as a category 1 treatment for patients with TGCT, becoming the first and only systemic therapy to receive a NCCN category 1 recommendation in TGCT.

“The NCCN guidelines were published for health care providers back in 2019, but they have since come out with new guidelines for patients,” said Howard Rutman, MD, a teaching attending at Mount Sinai School of Medicine and an attending at Montefiore Medical Center.

The recommendation was based on the results of the phase 3 ENLIVEN study which also served as the basis for the August 2019 FDA approval of pexidartinib for the treatment of adult patients with symptomatic TGCT that is associated with severe morbidity or functional limitations and not responsive to improvement with surgery.2

In part 1 of the trial, the small molecule, CSF1R receptor inhibitor led to a 38% overall response rate (ORR; 95% CI, 28%-52%) versus 0% (95% CI, 0%-6%) with placebo after 25 weeks of treatment, based on central review of MRI scans (P <.0001).3

The ENLIVEN study was divided into 2 parts. In the first part, 120 patients with symptomatic advanced TGCT, in whom surgery would have been detrimental, were randomized to receive pexidartinib (n = 61) or placebo (n = 59) at 1000 mg daily for 2 weeks followed by 800 mg daily for 22 weeks.

Eligible patients had histologically confirmed, advanced, symptomatic TGCT with at least 2 cm of measurable disease per RECIST v1.1 criteria. Fifty-nine percent of patients were female, and 88% of patients were Caucasian. The median age was 45 years (range, 18-79), 8% of patients had upper extremity involvement, and the remaining 92% had lower extremity involvement.

The percentage of patients achieving a complete or partial response (PR), assessed with centrally read MRI scans using RECIST 1.1 criteria, following 24 weeks of treatment served as the primary end point of the trial. Key secondary end points included range of motion response by tumor volume score (TVS), Patient-Reported Outcomes Measurement Information System physical function, stiffness, and measures of pain reduction.

Results from part 1 also demonstrated a complete response rate of 15% and a PR rate of 23%. The median duration of response (DOR) was not reached with pexidartinib and was not available with placebo. Ninety-six percent of patients had a DOR of at least 6 months, and 50% of patients had a DOR of at least 1 year.

At a median follow-up of 6 months, none of the responders in the trial progressed. Tumor response, assessed by TVS, was 56% (95% CI, 43.3%-67.5%) with pexidartinib versus 0% (95% CI, 0%-6.1%) with placebo (P <.0001). The responses also correlated with improved patient symptoms and function.

Regarding safety, serious adverse effects (AEs) were reported in 13% of 61 patients in the pexidartinib group and 2% of 59 patients in the placebo group. The most common pexidartinib-associated AEs were hair color changes (67%), fatigue (54%), aspartate aminotransferase increase (39%), nausea (38%), alanine aminotransferase increase (28%), and dysgeusia (25%).

A total of 3 patients who received pexidartinib had aminotransferase elevations at least 3 times the upper limit of normal (ULN), with total bilirubin and alkaline phosphatase at least 2 times the ULN indicative of mixed or cholestatic hepatotoxicity, one lasting 7 months and confirmed by biopsy.

Included in the prescribing information for pexidartinib is a Boxed Warning regarding the risk of serious and potentially fatal liver injury. Liver tests should be monitored prior to start of treatment and at specified intervals during therapy. Should liver tests become abnormal, pexidartinib may need to be withheld, the dose reduced, or be permanently discontinued, depending on the severity of the liver injury. The agent is only available through the Risk Evaluation and Mitigation Strategy Program.

“TGCT is a rare tumor. It is difficult to diagnose, and it presents often with nonspecific symptoms, such as joint swelling, stiffness, or loss of range of motion. By seeing a multidisciplinary team, patients can access the most recent treatments, which now includes systemic therapy with Turalio,” said Rutman, who is also vice president of medical affairs at Daiichi Sankyo, Inc.


  1. NCCN has included pexidartinib (Turalio) as a category 1 recommendation for TGCT/PVNS in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma. News release. July 15, 2020. Accessed July 16, 2020.
  2. FDA approves first therapy for rare joint tumor. FDA. News release. August 2, 2019. Accessed July 16, 2020.
  3. Pexidartinib versus placebo for advanced tenosynovial giant cell tumor (ENLIVEN): a randomised phase 3 trial. The Lancet. 2019;394(10197):478-487. doi:10.1016/S0140-6736(19)30764-0