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Soft Tissue Sarcoma Case Studies

Use of Olaratumab for STS for Undifferentiated Pleomorphic Sarcoma in the Retroperitoneum

Published Online:Nov 01, 2016
Brian Van Tine, MD, PhD, reviews the goals of therapy and treatment options in advanced soft tissue sarcoma, and discusses dosing strategies and treatment options using case-based scenarios.

Advanced Soft Tissue Sarcoma with Brian Van Tine, MD, PhD Case 1

Brian Van Tine, MD, PhD: So, I think one of the most interesting things we actually really truly need to figure out in soft-tissue sarcoma is what the mechanism of action is. We know that this is a monoclonal antibody platelet-derived growth factor (PDGF) receptor-α. But, the real question is, is it working in the tumor, on the inside of the tumor, or is this something that’s happening in the microenvironment? If you begin looking at where PDGF is expressed, sometimes it’s in the microenvironment, sometimes it’s in the tumor. The working hypothesis is that this may alter the microenvironment in a way where the tumor actually has a hard time spreading after the treatment with olaratumab. But, that treatment must be in combination with at least an anthracycline at this time.

In this patient with nonresectable disease where we’re more than likely not going to be able to cure them, giving them the best overall survival is my goal. And so, to treat him, we’re going to use the phase II dosages of both doxorubicin and olaratumab. In the phase II trial, we gave 8 cycles of doxorubicin at 75 mg/m2 on day 1 of a 21-day cycle. Olaratumab was given on day 1 and day 8. Growth factors were allowed, and they could be given on day 2 or day 8. If you take that together, what we’ll do is 8 cycles of that. If the patient makes it all the way through 8 cycles of combination therapy, what we do, at that point, is we stop the doxorubicin and we continue them on olaratumab maintenance until the time of progression. And all through this course, we’ve used olaratumab at 15 mg/kg.

I think one of the most important things when bringing a new drug into a clinical practice is to understand its safety. Going back to the original phase I data, I think it’s important to realize that the addition of olaratumab to doxorubicin did increase the amount of mucositis, nausea, vomiting, and diarrhea, but just by a little bit. In general, as a sarcoma clinician, if you went across the studies, statistically it was higher. The one thing that stood out to me, especially in the Midwest…I work in the Aspergillus belt, and because of that, it’s important to know how to pre-medicate appropriately. But, if you work on a coast, this is less of a consideration.

Having reviewed the safety, now we get to talk about the more exciting thing, which is the efficacy. If we look at the overall survival data, if we look at the combination of doxorubicin with olaratumab and compare it to the patients that got doxorubicin followed by olaratumab, we find a statistically significant 11.8-month overall survival for the combination. If we look at progression-free survival, it was 6.6 months for the combination versus 4.1 months for just monotherapy of doxorubicin alone. This did border on statistical significance, but it was not statistically significant to the trial.


Case Scenario 1:

  • The patient is a 36 year-old Caucasian man, referred to a center of excellence after diagnosis of a high-grade undifferentiated pleomorphic sarcoma located in the retroperitoneum.
  • The tumor is large (8 cm), deeply seated, and unresectable because of its location and invasion of major vascular structures.
  • His performance status is 0.
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