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Soft Tissue Sarcoma Case Studies

Use of Olaratumab for LMS Metastatic to the Peritoneum and Lungs

Published Online:Oct 25, 2016
Mark Agulnik, MD, 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 Mark Agulnik, MD Case 2



Mark Agulnik, MD: Standard-of-care treatment for soft tissue sarcomas is generally different, depending on which histology you’re using. There are some generalities, of course. When we look specifically at a uterine leiomyosarcoma, the options for her for first-line therapy become an adriamycin-based therapy—whether or not we want to combine adriamycin with ifosfamide, combine it with dacarbazine, or we’re looking to combine it with novel therapeutics and targeted agents like olaratumab. The other options, for a patient like this, would be are we looking towards gemcitabine and Taxotere? However, we would anticipate that the toxicity profile of a combination gemcitabine and Taxotere will be slightly worse than that of adriamycin as a single agent.

With the availability of olaratumab on the market, one has to really question about where do we sequence this, what do we combine it with, and what will essentially happen with patients moving forward. The anticipation based on the overwhelmingly impressive data from the phase Ib and phase II are that, given the survival advantage of the combination of adriamycin with olaratumab, that would then become the first-line therapy for patients. Perhaps, in the general treatment approach, one is moving ifosfamide off of the initial treatment regimen, perhaps removing single-agent adriamycin out of the armamentarium, which we’re using for treatments of patients. And, we’re probably sequencing gemcitabine and Taxotere as a second-line agent and maintaining adriamycin or doxorubicin-based combination therapy as a first-line agent.

The clinical trial of the phase Ib and II, which reviewed patients with metastatic or unresectable disease, showed that the addition of olaratumab to doxorubicin did increase the toxicity profile slightly. It didn’t really increase the grade 3 or 4 toxicity dramatically, and so that’s reassuring. But, what it was able to do is profoundly impact overall survival for patients, and extend survival by almost a year versus patients who didn’t receive the combination therapy.

The phase II data for olaratumab and doxorubicin were very impressive because it was one of the first studies that actually used more doxorubicin than what’s traditionally used and what has been used in prior phase III clinical trials of doxorubicin with a second agent. And, so, while most people have used 6 cycles at 75 mg/m2 of doxorubicin, here is a trial that now expanded that and used 8 cycles of therapy at 75 mg/m2. What is unique in this situation is that there was the addition of Zinecard for the last 4 cycles. This would have given some cardioprotectant, which the concern is that people who have more doxorubicin, it will essentially affect the heart in a negative way.
    
    What always becomes important to think about, when new drug combinations come to market or new drugs come to market, is what do you do with all those patients who had previously been treated who didn’t have the availability of this drug for first-line therapy, if we are very excited about now using this as first-line therapy? I do think it is very important to look at our patients who have previously been treated. It becomes very easy. If a patient had previous treatment with gemcitabine and Taxotere, or another combination that is not doxorubicin-based, then we could use this as a second-line agent or a third-line agent as a combination of doxorubicin and olaratumab. The harder thing is for patients who have had a number of cycles of doxorubicin. They may have maxed out their lifetime dose of it, and perhaps they’re not eligible for the addition of olaratumab to any other treatment. Therefore, perhaps, one could look at this as a single agent for those patients, depending on what the labeling by the FDA is.

The other issue here is going to be if someone only had 2 cycles of adriamycin or doxorubicin, and then progressed on that, do you want to cycle it back in, the doxorubicin, but this time add the olaratumab to see if the patient could derive the benefit of olaratumab and perhaps then using it over 6 cycles instead of 8 cycles?

 

Case 2:

  • The patient is a 61 year-old Caucasian woman, diagnosed with uterine leiomyosarcoma (LMS) metastatic to the peritoneum and lungs.
  • The tumor is 11 cm in diameter
  • Her performance status is 1
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