DR VAN TINE: A lot of standards of care have actually just changed. Not to divert too quickly, but olaratumab is a monoclonal antibody of a platelet-derived growth factor receptor alpha. Just published in Lancet was the randomized Phase II of doxorubicin with olaratumab versus doxorubicin followed by olaratumab. And what they found in that trial was a year overall survival in patients that got the combination.

And because of that, it was granted contingent FDA approval. The Phase III is accrued, and it’s waiting to be read out in the next couple of years. And until that happens, I think what we found is we have a new agent that’s really altered metastatic front-line therapy.

DR LOVE: And I want to go through that, actually. Certainly it’s a huge thing that’s just happened in the field. But again, can you kind of paint the picture of how you look at sarcomas, so the newly approved drugs is something that happens it seems like all the time now in oncology. So this is just approved. It’s a great way to get started. And I’m sure oncologists are going to be very interested in this. But again, what’s the overall construct to how you see soft tissue sarcomas?

DR VAN TINE: So I think the first question you have ask when looking at a patient is what their stage is. And the approach to a Stage III and a Stage IV patient is very different. A Stage III or II patient is a high-grade sarcoma that needs aggressive management. A Stage I tumor usually more surgical tumors. So I think this is a conversation more for medical oncologists. So let’s just focus on Stage II and III.

In Stage II and III, the first question after stage is diagnosis. And so things like synovial sarcoma you are more than likely to start off with a neoadjuvant approach, depending on what center you’re at — this is where this gets complicated very quickly — and give them doxorubicin with ifosfamide as a neoadjuvant strategy, followed by then either radiation or surgery and surgery or radiation. And that would be the approach to a Stage II or III synovial sarcoma. If you move on to a retroperitoneal sarcoma, you may just elect for surgery. And then the radiation questions gets very difficult very quickly. This is why this experience with multidisciplinary teams planning these out correctly and margin status is so important.

As you move on to Stage IV you begin, then, to ask, what sort of Stage IV are they? Is this a patient with extensive metastatic disease, such that the likelihood of cure isn’t on the table, they have thousands of lung mets or a bunch of cannon balls. And how would you approach that patient? Or is this a patient with an isolated lung met or 2 in the same lobe? And I think these patients are actually approached very differently.

With the addition of this new drug, this becomes a much more complex conversation. Because if you’re going to go for response, you’re probably still going to trend toward doxorubicin with ifosfamide. If you’re going to palliate, you’re now going to probably use doxorubicin with olaratumab.

And that’s why I say this is a great timely conversation, because that is a conversation that’s going on within the field. And this is what’s going on right now. Which is, you can give somebody a longer overall survival with a less toxic regimen if you’re not trying to cure them. Whereas if you are going to take that patient for cure, you’re probably going to still go with an ifosfamide-based regimen because the response rate’s higher. And so really, it’s intent at this point.

Classification, incidence and management of sarcomas

Integration of the recently FDA-approved agents trabectedin and eribulin into the treatment algorithms for metastatic liposarcoma and leiomyosarcoma

Recent FDA approval of olaratumab in combination with doxorubicin and integration into the treatment algorithm for advanced STS

Role of tyrosine kinase inhibitors and immune checkpoint inhibitors in STS