Richard F. Riedel, MD, Medical Oncologist, Duke Health, discusses tyenosynovial giant cell tumors (TGCT), including:
– Challenges of diagnosing these rare, benign tumors
– Current management strategies
– Emerging treatment options
– Advice to newly diagnosed patients
Transcription
My name is Richard Riedel. I’m a board-certified medical oncologist. I work at the Duke Cancer Institute in Durham, North Carolina. I have expertise in soft tissue and bone sarcomas, as well as other soft tissue tumors, including TGCT. I’ve been on faculty for about 16 years.
Well, TGCT is also known as Tenosynovial Giant Cell Tumor. Historically, it went by another name called PVNS or Pigmented Villonodular Synovitis. That latter term is now antiquated and not used. But TGCT is not a cancer per se, but it is an abnormal soft tissue growth that can affect the joints, most commonly the knee.
There are two types: a limited type, which is treated largely with surgery alone with the vast majority of patients being cured, and then a more diffuse type, which is more aggressive and involved, for which surgery has become less favored in recent years due to the introduction of some novel systemic therapies.
I think the diagnosis certainly can be delayed in part because there are a lot of other more common conditions that can mimic the symptoms associated with TGCT. For example, knee swelling, knee stiffness, pain, might be attributed to trauma, a sports injury, maybe some arthritic changes. It’s not until symptoms persist or don’t respond to more conservative therapies like anti-inflammatories or physical therapy where imaging is done, and then the radiographic findings then raise concern for an alternative diagnosis, in this case, TGCT.
These patients many times will present through the primary care provider. They could see a rheumatologist. They could see a sports medicine orthopedist. I think any of those have the ability to diagnose through a biopsy. Radiographic findings can certainly be highly suggestive of a TGCT diagnosis, but diagnosis really requires a biopsy, in my opinion.
I think the management is in evolution. Historically, these patients were treated with surgery, and at least for the diffuse type of TGCT, the treatment course was really often resulted in multiple surgeries because of high recurrence rates or because of incomplete excisions. That has changed in recent years with the introduction of some novel therapies that target really what’s known as the molecular driver of the disease, something called CSF-1 receptor. In doing so, it really has downplayed the role of surgery for diffuse type TGCT, and now systemic therapy, I would argue, is the preferred initial approach for these patients.
Well, the first FDA-approved agent was approved now about two years ago or so, a therapy called Pexidartinib. That is an oral small molecule inhibitor. It targets the CSF-1 receptor, which is involved in the pathogenesis of the disease, and in a phase three study called the ENLIVEN Study, Pexidartinib, compared to a placebo showed improved response rates, better disease control, as well as significant improvement in symptoms. That was introduced a couple of years ago, and I think really has changed the treatment approach for these patients.
Since that time, there are other therapies that are in active development and active exploration. Most recently, within the last couple of months, we heard top-line data from a study called MOTION, which looked at Vimseltinib, another oral small molecule inhibitor, and at least on the data available publicly, response rates compared to a placebo, were improved, as well as significant improvements in symptom burden, as well as other objectives that were evaluated in the study. We’re still waiting to see the full data, but a lot of enthusiasm and a lot of activity currently in the TGCT space.
Well, I think at least historically, we did not have an FDA-approved therapy. We would use off-label use of medicines like Imatinib or Nilotinib, which had activity against CSF-1 receptor. But these newer agents are much more potent and selective. I didn’t mention this, but there are also strategies looking at intra-articular approaches, therapeutics as well as intravenous therapeutics.
I think the enthusiasm is that these newer therapies really are more selective and highly target the signals that are thought to be involved in the pathogenesis of the disease. What’s particularly exciting about some of the newer therapies is potentially, although, again, we haven’t seen the full data yet, but potentially decreased hepatotoxicity than what has been seen in a Pexidartinib of the first FDA-approved agents.
To learn more about this rare disease, visit our TGCT Learning Center here.
