Pexidartinib Demonstrates Great Tumor Response in Tenosynovial Giant Cell Tumors

Brian Van Tine, MD, Sarcoma Program Director, Division of Medical Oncology, Washington University, St. Louis, Missouri, discusses results from the ENLIVEN trial, which evaluated pexidartinib, a CSF1 receptor inhibitor, in patients with tenosynovial giant cell tumors (TGCT).

Transcript

My name is Brian Van Tine, and I'm the Sarcoma Program Director at Washington University in St. Louis, where I am the medical oncologist. I was an active investigator within the ENLIVEN trial that we'll be discussing today.

The ENLIVEN trial focused on one disease with 2 different names. The first name that we'll focus on is a disease called tenosynovial giant cell tumor, which is actually also known as pigmented villonodular synovitis.

This is one disease that actually has 2 names depending on where you are in the world, and over time, this is a disease that most medical oncologists will have to get to understand better.

What's interesting about this disease is it is a tumor, but not necessarily a cancer. It's driven by an amplification on chromosome 1p13 that drives colony-stimulating factor 1.

One of the most interesting parts of the descriptive name of pigment villonodular synovitis is what those terms actually mean. The pigmented part comes from the breakdown of blood products within the tumor.

The synovitis is a descriptive term for all the immune infiltrants that are found in this heavily immuno-infiltrated tumor that usually grows within synovium. The other name of that is tenosynovial giant cell tumor based on what the cells look like, but I think the older name for this is more descriptive of what patients undergo.

This is usually a disease that grows within joints that is actually usually associated with a lot of pain. There's now a new drug that's been FDA approved called pexidartinib, which is for the treatment of surgically-refractive tenosynovial giant cell tumor.

The ENLIVEN trial was a very complex-driven trial that took 121 patients and assigned them to either pexidartinib or a placebo. Then after six months, patients were allowed to cross over to pexidartinib if they had been on placebo or if they progressed on placebo.

This also was an interesting trial in that quality of life metrics were heavily focused upon. They also included things like range of motion and pain scores.

If you look at the overall trial, the average patient was 44 years old, though there was a range of between 18 and 79, with slightly more women than men. It was predominantly within the Caucasian population, but this trial was done worldwide.

In terms of locations of tumors that entered the trial, the most likely place was from the knee, and then this was followed by ankle and hip.

The average patient had had greater than one surgery, but some were just not surgically resectable. Previous treatments for most patients had either included none—this is mainly treated by surgeons—or occasionally nilotinib or imatinib.

What they found is that looking at the placebo-controlled arm no patients responded within a RECIST criteria to placebo. If you look at change, in terms of tumor diameter from baseline for patients with pexidartinib, they found that 24 of 61 patients had tumor response by RECIST, with a number of patients having complete responses.

One of the problems with looking at a response rate in a tumor like pigmented villonodular synovitis, or tenosynovial giant cell tumor, is that the shape of the tumor is very complex, since it wraps around knees, is not very amenable to being studied by RECIST.

One of the correlatives and more interesting things they developed for this trial was a tumor volume score. When you use a tumor volume score, you're looking at more of the entire tumor as it responded. Greater than 50% of people responded to pexidartinib, but not to placebo.

In terms of side effects, there was dramatic change in hair color. This drug turns hair color white, just like many of the other TKIs. There was an association with nausea, diarrhea, abdominal pain, and vomiting that is not uncommon for this class of drugs.

Patients also complained of fatigue with greater than 50% of people complaining of fatigue. But more interestingly, 36% of patients on placebo also complained of fatigue.

There was a number of episodes of increased LFTs as a result of pexidartinib. This did lead to premature ending of this trial prior to complete enrollment. Safety had to be assessed.

There is now a REMS program involved in making sure that patients are adequately monitored or AST, ALT, and liver function that can be altered as a result of the use of pexidartinib.

Overall, this is a drug for pigmented villonodular synovitis, or tenosynovial giant cell tumor with great efficacy, great improvements in pain scores and functionality for patients that can no longer undergo surgery.

As such, it's now available through our REMS program, and there should be a collaboration between both the orthopedic and sports medicine doctors who treat this and the medical oncologists that may be able to improve quality of life prior to extreme surgeries that can be done.