William D. Tap, MD: Let’s now switch to a 55-year-old female who has had multiple recurrent retroperitoneal de-differentiated liposarcoma. Let’s argue this patient had a resection 6 months ago and we’re now dealing with another recurrence. We have to start thinking about systemic therapy in this patient, historically. People questioned sensitivity to chemotherapy, but maybe we’re talking response rates versus stability or affecting the de-differentiated component. What are some of your thoughts? Actually, 2 new drugs were recently FDA approved, trabectedin and eribulin, after frontline chemotherapy. What are some of the thoughts about the de-differentiated liposarcoma?

Victor M. Villalobos, MD, PhD: You have several similar drugs as the other STS [soft tissue sarcoma]. You have doxorubicin and olaratumab. I think trabectedin can be extremely effective. The problem is that most chemotherapies, you’re right, are not incredibly effective in this disease type and that’s why—I hate to sound the same bell again—clinical trials are really important. We have a trial ongoing right now with selinexor to see if that is going to be effective. It’s a randomized study against placebo. MDM2 inhibitors are in development right now. As heterogeneous as sarcomas can be, well-differentiated and de-differentiated liposarcomas have a very distinct signature that is actually targetable.

While we haven’t made massive gains yet, I think we’re getting there. Dr. Dixon’s study looking at palbociclib had some efficacy, not just in the de-different liposarcoma but also in the well-differentiated liposarcomas. With MDM2 inhibitors, we’re moving forward. But I think getting patients involved with trials early on is really important. Trabectedin and eribulin work well.

Richard F. Riedel, MD: I agree. I think if we’re talking outside of a clinical trial in the context of the currently available therapies, for this patient frontline it’s doxorubicin/olaratumab unless I need to get a robust response; then it’s doxorubicin/ifosfamide. In the second-line setting, right or wrong, I would consider gemcitabine-based regimen. In the third-line setting, I think you have a couple of options. You can consider trabectedin or you can consider eribulin based on overall survival benefit. Trabectedin showed PFS [progression-free survival] benefit. After that, I think dacarbazine.

Kristen N. Ganjoo, MD: I would add immunotherapy to the de-differentiated liposarcomas with ipilimumab and nivolumab, which in the trials we did see some responses with.

William D. Tap, MD: Some of the well-differentiated patients responded.

Kristen N. Ganjoo, MD: Some of the well-differentiated, yes.

Richard F. Riedel, MD: And off-label. Outside of the clinical trial. I wouldn’t routinely recommend it.

William D. Tap, MD: We’ll put an asterisk right above it.

Jonathan C. Trent, MD, PhD: Rich is the conscience of the panel. The only other thought that I would have on this patient is, if this is liver-only disease, one could consider hepatic arterial embolization or radiofrequency ablation. With de-differentiated liposarcoma, we’ve published several case reports in a small series on using NanoKnife, irreversible electroporation, and it’s particularly effective in liver metastases.

Kristen N. Ganjoo, MD: We’ve used a lot of radioembolization with Yttrium-90, and we’ve had some success with that.

William D. Tap, MD: It’s challenging because oftentimes, the retroperitoneal liposarcomas do have distant metastases, but it’s not as common as local spread. These are often patients with multiple resections, so they often only have 1 kidney. They’re also patients for whom you worry more about the local side effects of the disease. But when you can push these tumors into stability, just like with leiomyosarcoma, you can get serious PFS rates.

Victor M. Villalobos, MD, PhD: Because most patients who have active disease have minimal symptoms from the disease itself.

William D. Tap, MD: That’s right.

Victor M. Villalobos, MD, PhD: And so, you also want to make sure that you’re trying to balance out the efficacy of the drug with the toxicity, because patients live years. These patients live a long time.

Jonathan C. Trent, MD, PhD: To your point about the heterogeneity, even the de-differentiated component can grow very slowly in some patients.

Victor M. Villalobos, MD, PhD: I’ve seen some well-differentiated disease grow really rapidly. They just get really full, and after that, it can be very tricky.

William D. Tap, MD: A tumor that you’re always working on with your surgeons and other doctors to control.

Victor M. Villalobos, MD, PhD: I agree, even for metastatic disease. I will oftentimes need surgeries again.

William D. Tap, MD: Yes, but I think these cases are nice because they’re bringing together the sequencing that we think about.

Transcript Edited for Clarity