A novel targeted drug shows promise in treating patients with advanced pigmented villonodular synovitis (PVNS), a rare neoplastic joint disorder, according to new phase I data from Memorial Sloan Kettering Cancer Center and other institutions highlighted to media today in advance of the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), which will take place from May 30 to June 3 in Chicago.
At the time of interim analysis, 11 of 14 evaluable patients (79 percent) had a partial response to the drug and three patients had stable disease. The mean tumor size reduction among all 14 patients was 61 percent.
The drug, PLX3397, is a tyrosine kinase inhibitor that potently inhibits the colony stimulating factor 1 (CSF1) receptor kinase, a driving force in the development and growth of PVNS.
“By taking this drug that potently inhibits a single genetic process, several patients with advanced PVNS appeared to experience, in a relatively short amount of time, relief from pain and stiffness as well as marked improvement in joint function, all with minimal side effects,†says William D. Tap, MD, lead author on the study and Chief of the Sarcoma Medical Oncology Service at Memorial Sloan Kettering. “This is a proof-of-principle study that demonstrates the powerful clinical benefit of matching the right drug to the right molecular abnormality and further spurs excitement over the potential of precision medicine.â€
PVNS is a rare and destructive joint disorder that affects approximately 600 young and middle-aged adults in the United States each year. Patients with PVNS experience an inflammation and overgrowth of the synovium, or joint lining, which results in swelling, pain, and reduced mobility in the affected joint. PVNS is not considered a cancer because it usually remains within a single joint rather than metastasizing, and is not known to cause death. The knee is the most common site affected, followed by the hip.
PVNS tumors express high levels of CSF1, a protein that continually attracts an abundance of cells with CSF1 receptors, such as macrophages, to the joint. This influx of cells causes the inflammation and overgrowth of the joint lining, which can destroy the joint over time.