DR POLLACK: This is a monoclonal antibody against PDGFR alpha. And it was tested in a Phase II study that had about 60-something patients on each arm. And patients were randomized to receive either doxorubicin alone or doxorubicin plus olaratumab. And the results were really striking.

Unlike your typical trial where the progression-free survival benefit is usually strong and then maybe you’ll see something in overall survival, in this case there was a trend toward an improved response rate and a progression-free survival benefit in the olaratumab arm, but they weren’t statistically significant. But there was a huge benefit in terms of overall survival.

So the overall survival in the olaratumab arm was 26 months versus about 14 months in the doxorubicin-alone arm. And this was highly statistically significant. And that’s what led to the conditional approval of olaratumab for soft tissue sarcoma in combination with doxorubicin.

DR LOVE: What was seen or what has been observed in terms of toxicity?

DR POLLACK: It’s pretty well tolerated. I mean, there is more cytopenias when you combine olaratumab plus doxorubicin. There’s a little bit more fatigue and nausea. A little bit more diarrhea. But generally I wouldn’t say that there’s a qualitative difference in the experience of a patient going on doxorubicin plus olaratumab versus doxorubicin alone.

DR LOVE: When you think about the biology of soft tissue sarcomas, how do you see this drug actually having its therapeutic benefit?

DR POLLACK: It’s really confusing, because they actually did a correlative analysis where they looked at PDGFR alpha in the tumors to see if that would predict who responded to olaratumab or not. And they didn’t really see an increased benefit in the patients that had strong PDGFR alpha expression, right? That pretty much didn’t make a difference.

I’m not really sure how this drug works without causing a progression-free survival benefit but having this big increase in overall survival. Some people think that maybe it’s changing the biology of the tumor, that it’s making the tumor less aggressive so that even as you go on to future lines of treatment, the tumor is just not being as aggressive. But I think that we really have to slow down.

And there’s a Phase III trial that’s coming that has finished accruing. We’re waiting to see what the data is. I personally wouldn’t be surprised if in the Phase III trial data maybe the PFS benefit is a little bigger and the OS benefit is a little smaller. And we’ve had a number of trials in sarcoma that have looked really good in Phase II and then in Phase III didn’t come through. So I’m really excited that we have another drug.

For sure, I’m using this in the patient that I’m treating off protocol in the up-front setting in the metastatic setting that hasn’t received chemotherapy before or hasn’t received an anthracycline before. But I think that we want to see what the Phase III trial result is.

• Biology, incidence and management of sarcomas
• Etiology and risk factors for the development of soft tissue sarcoma (STS)

• Mechanism of action and tolerability of trabectedin for liposarcoma and leiomyosarcoma
• ET743-SAR-3007: Progression-free survival benefit with trabectedin versus dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy
• Improvement in overall survival with eribulin versus dacarbazine for patients with previously treated advanced liposarcoma or leiomyosarcoma
• Case discussion: A 55-year-old woman with Li-Fraumeni syndrome and a history of sarcoma is diagnosed with a high-grade, unresectable liposarcoma in the mediastinum
• Integration of trabectedin and eribulin into the clinical management of leiomyosarcoma and liposarcoma
• FDA approval of trabectedin for patients with unresectable or metastatic liposarcoma or leiomyosarcoma who experience disease progression after receiving an anthracycline regimen

• Use of the recently FDA-approved PDGFR alpha monoclonal antibody olaratumab in combination with doxorubicin as front-line therapy for advanced STS
• Overall survival benefit with the addition of olaratumab to doxorubicin for patients with STS in the randomized Phase II JGDG trial
• Mechanism of action, efficacy and tolerability of olaratumab

• Activity and tolerability of the tyrosine kinase inhibitors regorafenib and pazopanib in patients with STS
• Use of pazopanib for patients with advanced STS
• Activity of immune checkpoint inhibitors in patients with STS