Of the 14 patients, 11 had a PR and three had SD, for an ORR by TVS of 79%; disease control rate was 100%. Mean tumor size reduction was 61%. Of the three patients who had prior TKI therapy, two had a PR and one, SD.

Along 18 patients, physician assessment of clinical change from baseline to the most recent visits showed a substantial clinical benefit: 13 (72%) had moderate to marked improvement in pain; 11 (61%) in stiffness, and 12 (66%) in daily activities.

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Dr. Tap, Chief of the Sarcoma Medical Oncology Service, said one of his patients, a woman who needed a cane to walk, was unable to straighten her knee, used narcotics for pain, and was unable to work—and for whom amputation was considered—was walking unassisted after 4 months of treatment with PLX3397, with an 85% response by TVS. After 2 weeks on PLX3397, PET standard uptake value decreased from 21.7 to 6.4, “arguing that the drug very rapidly can affect the inflammatory process, which is a hallmark of this disease.” She also had increased range of motion, was off narcotics, and had gone back to work.

Treatment-related adverse events (TAEs) included hair color changes (74%), fatigue (65%), nausea (48%), periorbital edema (26%), and dysgeusia (26%). Grade 3 or higher TAEs were anemia (1 patient, or 4%), hyponatremia (2 patients, 9%), elevated liver enzymes (2 patients, 9%), fatigue (1 patient, 4%), diarrhea (1 patient, 4%), and neutropenia (1 patient, 4%).

“PLX3397 is a very promising novel treatment for patients with advanced PVNS,” Dr. Tap concluded.

A phase 3 study of PLX3397 is under discussion.

To date, there is no Food and Drug Administration–approved treatment for PVNS, which affects about 600 primarily young people in the United States annually. Previously, a study with imatinib reported a 19% overall response rate in 27 patients. Misdiagnosis is common, Dr. Tap said. Surgery—joint replacement and amputation—is standard of care. The disease is often diffuse, has a high recurrence rate, and is believed to be underreported.

The research was supported by Plexxikon Inc. 


  1. Tap WD, Anthony SP, Chmielowski B et al. Abstract 10503. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.