TSGCT: Novel Agents and Future Directions in Care
Transcript:
Shreyaskumar R. Patel, MD: A comment about what else is out there. There are clinical trials going on looking at other ways of inhibiting CSF1 receptors. Five Prime [Therapeutics] has an antibody called cabiralizumab. This trial has been open at a few different centers. It’s an intravenous infusion over about half an hour, given either every 2 weeks or 4 weeks. It’s close to accrual right now. I don’t think the data have been analyzed, but we’ll see how a monoclonal antibody approach to inhibition of the CSF1 receptor and the ligand works and how that compares to the current standard of care.
There is another small molecule trial for a drug from Deciphera Pharmaceuticals called DCC-3014 (NCT03069469), another CSF1 receptor inhibitor, that hasn’t opened for accrual yet. It’s certainly another trial that is planned. Finally, I’m aware of one other broad-spectrum tyrosine kinase inhibitor called surufatinib. It used to be called sulfatinib. The drug has been tested extensively in pancreatic and extra-pancreatic neuroendocrine tumors. It’s on target for approval for that entity, but it happens to also be a potent CSF1 receptor inhibitor. There will be an arm of a few patients with PVNS [pigmented villonodular synovitis], the diffuse variant who need systemic therapy, to be tested.
The summary of this would be that there are a couple of clinical trials that have been conducted and are ongoing that will broaden the horizons, if you will, and give us a little bit of perspective on what would be the best sequence and way to incorporate these drugs. Gina, Bob, do you have anything additional to add about systemic therapy in general or multidisciplinary care?
Gina Z. D’Amato, MD: We’ve all—us on the panel, I’m not sure about the audience—treated patients with pexidartinib, and patients are having great responses. I have a patient from the original phase I trial 4 years out who’s a firefighter. When we try to make treatment decisions, surgery versus systemic therapy, we want to look at the acute toxicities, but we also want to look at the long-term toxicities and the long-term complications. When we say that they’re not surgically resectable, a surgeon can always do a surgery, but what are the long-term complications of this? If you have an amputation, you can’t get the leg back.
With the drug, it does have some acute toxicities, but we’re not aware of any long-term toxicities. The hepatotoxicity that we see usually starts out in the beginning. We should be very diligent with the REMS [Risk Evaluation and Mitigation Strategy] program and check liver enzymes once a week. If we see any elevations in the liver enzymes, we have to check liver enzymes twice a week.
I have a patient now who had an amazing response in 3 weeks. She was unable to move her hand. She has disease in the metacarpal area, multifocal. Within 3 weeks, she had an amazing response. Unfortunately, she did develop liver toxicity and her bilirubin went as high as 9.9 mg/dL, but it’s on the downslope. We can’t re-treat her, but she’s had an amazing response with that. We know that she’s not going to have a long-term liver complication. She did have to go through the process of having the acute toxicities. We’re already weighing the risks and benefits of everything.
Being sarcoma experts, we also treat benign tumors such as giant cell tumor of the bone, desmoid tumors, and now this. With benign diseases, we don’t want to have long-term complications. Radiation can have a potential long-term complication. Surgery can have a potential long-term complication where this can’t, and you can stop the drug. That’s the conversation that I have with the patient, but not every patient is interested. To me, I say it’s worth it. You can see how you do, and you can always stop. That’s how I approach the patients.
Shreyaskumar R. Patel, MD: Bob, any final thoughts?
Robert G. Maki, MD, PhD: A number of them, actually. I’m struck by the degree of response. We have a bunch of tyrosine kinase inhibitors that can block the CSF1 receptor, and imatinib is pretty darn good, but the volume metric reduction that you see with pexidartinib is a lot better. That must correlate well with the adverse effect profile or the symptoms that the patients experience improving so quickly.
One of the concerns is that people are stuck on the drug. If you do stop, you will have regrowth. The analogy there would be gastrointestinal stromal tumor, GIST, if you have metastatic disease. If you stop your kinase inhibitor, the tumor will grow back. Will there be drugs in the future or approaches in the future that do deliver that knockout punch to the tumor where people can stop therapy? That’s a point for research. It brings out this idea that if you are treating someone who’s presenting relatively early in their course, and it’s diffuse disease around the knee or the hip, you can propose neoadjuvant approach first using pexidartinib and then surgery. Will that be better than just doing the surgery upfront and waiting for people to recur? All these will be interesting research topics.
The last point is the primacy of the local control of surgery in taking care of this diagnosis, even with diffuse disease. As Dr Abraham and Dr Kim were talking about earlier, everybody should still have a surgery, if they can have it, as their first approach to this. That way, we’ll avoid medications that you have to take for a very long time, if for no other reason. Do not forget that local tumors still require that local approach. We have our own rose-colored glasses as medical oncologists about these wonderful medications, but we need to keep our eye on the ball as well.
Shreyaskumar R. Patel, MD: Any final thoughts, Dr Kim?
Tae Won B. Kim, MD: No. It’s been a great discussion. I hope it elucidates this multilevel thought process with the treatment of this tumor. My final words would be that for local disease, surgery is definitely the primary answer. For diffuse-type disease with multirecurrent, multifocal tumors, you need to have a multidisciplinary approach. That’s what you’re seeing here on this panel.
Shreyaskumar R. Patel, MD: Thank you very much. Final thoughts, Dr Abraham?
John A. Abraham, MD: I would just echo the things that the other panelists have said. I do still believe that surgery is the first-line strategy for most of these patients. As we get excited about the new medical therapies, it is important to remember that aggressive surgery really is the first line of treatment. Along the lines of what Dr Kim mentioned earlier, it is important to refer these patients to centers that have experience and have multidisciplinary groups, so that the full range of options can be investigated for each patient. Even the surgical techniques alone should be done by somebody with experience in it, because it becomes much more difficult the second time around, just as Dr Kim mentioned.
As a surgeon dealing with this frequently, my closing message is first, recognize that the disease exists and know how to diagnose it. Second, send patients to the right place to treat it. Third, be aware that there is a medical therapy that has proven thus far to be very good at controlling symptoms and bulk from this disease. That would be my message to the viewers.
Shreyaskumar R. Patel, MD: Very well said. My sincere thanks to the entire panel for a very rich and a very informative discussion. I also want to thank our viewing audience. We all hope that you found this OncLive Peer Exchange® to be useful and informative.
Transcript Edited for Clarity
