William D. Tap, MD: Let’s end with a final patient, we’ll say a 68-year-old male who has recurrent undifferentiated pleomorphic sarcoma and really metastatic disease, widespread metastases. He’s asymptomatic. How do you approach this patient?

Kristen N. Ganjoo, MD: Since the patient is asymptomatic, we can use drugs that have less toxicity. You could do the Adriamycin [doxorubicin]/olaratumab again. But I think pazopanib would be a good option as well.

Richard F. Riedel, MD: In the frontline setting?

Kristen N. Ganjoo, MD: Well no, I’m just going through Adriamycin/olaratumab and then you can go on. But in the frontline setting, I would say Adriamycin/olaratumab if the patient can tolerate it. If not, the Ganjoo every-2-week regimen of gemcitabine/docetaxel has been very successful in undifferentiated pleomorphic sarcomas.

William D. Tap, MD: Ifosfamide or AIM [doxorubicin/ifosfamide/mesna]?

Richard F. Riedel, MD: For that 68-year-old, if they’re asymptomatic, I don’t see a need to get a significant response, assuming they have a significant burden of disease. I agree with doxorubicin in combination with olaratumab given in the frontline. If their patient were a little bit older or if I had concerns about standard doxorubicin or the combination with olaratumab, I would actually consider liposomal doxorubicin as a single agent.

William D. Tap, MD: We haven’t mentioned liposomal doxorubicin before. Can you just give some of your thoughts?

Richard F. Riedel, MD: There has been at least 1 phase II study of about 100 patients—I think it was performed in the United Kingdom—looking at doxorubicin standard dose compared to a liposomal variant at 40 mg/m² monthly. At least in that randomized phase II trial, the efficacy was similar between the two. For me, I think it’s a very reasonable option, particularly if I have concerns about a patient’s ability to tolerate standard-dosed doxorubicin.

William D. Tap, MD: Any other thoughts with UPS?

Victor M. Villalobos, MD, PhD: I think it depends on how the behavior of the UPS is. If this isn’t incredibly aggressive, I think immunotherapy is going to maybe play a big part, whether it be in a clinical trial or off-label use, frankly. I had personal experience, as well as experience on trials, showing these are the patients who can respond really dramatically to this. It’s hard to justify that if the tumors are doubling every 2 weeks. You need to have time to respond, but I’ve seen some really dramatic long-term responses in the UPS protocol for immunotherapies as well, including some antibodies with conjugates.

Richard F. Riedel, MD: I just want to temper the enthusiasm for immunotherapy. I completely agree. If there’s a histology that’s going to respond to immunotherapy, UPS is probably going to be it. But I really would caution the viewers about jumping to immunotherapy in the frontline setting.

Victor M. Villalobos, MD, PhD: Oh, no, I don’t think so in the frontline. But I think at some point, this patient, if they can wait that long to get efficacy of immunotherapy, should get it.

Kristen N. Ganjoo, MD: I want to change my answer. I think one of the things that you said here was asymptomatic, but it depends on how much disease they have. They could be asymptomatic one minute, and then 2 hours of millimeter growth later, they could be having hydronephrosis and all those kinds of things. I think I would still go with Adriamycin/olaratumab to treat this patient, even though he’s asymptomatic. That was my correction.

William D. Tap, MD: Sounds great.

Richard F. Riedel, MD: And then switching to immunotherapy.

Jonathan C. Trent, MD, PhD: I agree with Kristen.

William D. Tap, MD: You guys are agreeing, this is good.

Jonathan C. Trent, MD, PhD: I would treat with a doxorubicin-based frontline regimen, doxorubicin/olaratumab. I have not examined this patient. If he could tolerate a doxorubicin doublet with olaratumab, that would be one consideration, particularly on a clinical trial because it’s not standard. And then, I would still have the goal of treating as aggressively in the shared decision making way he wants to be treated, realizing that even with pleomorphic sarcoma, there is a small cure fraction. I always preface it with the patient because I don’t want to be unrealistic. I don’t want to get anybody’s hopes up, but my approach is as the optimist, and we discuss that.

Victor M. Villalobos, MD, PhD: This is the patient as well who you’d want to get NGS [next-generation sequencing] for.

William D. Tap, MD: A great idea.

Victor M. Villalobos, MD, PhD: Because these are the patients who actually have these translocations that may be targetable. If you win the lottery and you have an NTRK fusion, there are excellent trials and excellent drugs available for that with dramatic responses.

Jonathan C. Trent, MD, PhD: We know so little about these unclassified and undifferentiated pleomorphic sarcomas. What other area of oncology doesn’t have a classification for their tumor?

Transcript Edited for Clarity