This article is more than 5 years old. Information may no longer be current.
Novel agent shows promise in treatment of rare joint neoplasm
Click Here to Manage Email Alerts
PLX3397, a selective CSF1R inhibitor, demonstrated safety and activity in the treatment of patients with tenosynovial giant-cell tumor, according to study findings published in The New England Journal of Medicine.
Tenosynovial giant-cell tumor (TGCT) is a rare, aggressive neoplasm of a joint or tendon sheath that is caused by a translocation of the CSF1 gene. Primary treatment for TGCT is usually surgery, however diffuse TGCT is difficult to resect and often requires more complex procedures such as total synovectomy, joint replacement or amputation as there are no approved systemic therapies.
PLX3397 (Plexxikon) is an oral targeted CSF1R inhibitor that induces longer tumor regression in most patients with TGCT.
William D. Tap, MD, chief of the sarcoma medical oncology service at Memorial Sloan Kettering Cancer Center in New York, and colleagues conducted a dose-escalation study of PLX3397 to prospectively focus on 41 patients with the disease and evaluate the agent’s efficacy and safety. Researchers then conducted a phase 2 dose extension study that included an additional 23 patients.
William D. Tap
The chosen phase 2 dose was 1,000 mg daily.
In the extension study, 12 patients with TGCT had a partial response (52.2%; 95% CI, 32-73) and seven patients achieved stable disease (30.4%). These data equated to a disease control rate of 82.6% (95% CI, 67-98).
At the time of data cutoff, median PFS had not been reached. Seventeen patients remained on the study at this time, seven of whom had been receiving treatment with PLX3397 for more than a year.
Responses tended to occur in the first 4 months of treatment and the median duration of response exceeded 8 months.
The most common adverse events included hair color change (74%), fatigue (65%), nausea (39%), dysgeusia (26%) and periorbital edema (26%).
“[We] show that blocking the CSF1 pathway in TGCT with an appropriately designed therapy can induce significant regressions in tumor volume,” Tap and colleagues wrote. “There is a growing list of oncogene-driven neoplasms that respond to drugs targeting the oncogenic driver. It appears that TGCT can be added to this list, given our results …
“Although TGCT tumors appear to be stable with respect to mutation and genetically homogenous relative to other oncogene-driven tumors, it will be important to determine whether resistance to CSF1R inhibition will occur and, if so, by what mechanism.” – by Anthony SanFilippo
Disclosure: The study was funded by Plexxikon. Tap reports consultant/advisory roles with, travel expenses and other personal fees from Advaxis, Ariad, Boehringer Ingelheim, EMD Serono, Eli Lilly, Morphotek and Plexxikon. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts