Soft Tissue Sarcoma Update, Issue 1, 2017 (Video Program)Overall survival benefit with the addition of olaratumab to doxorubicin for patients with STS in the randomized Phase II JGDG trial
3:42 minutes.
TRANSCRIPTION:
DR VAN TINE: The trial was a randomized Phase II with about 66 patients in each arm, of doxorubicin given for 8 cycles with olaratumab given every cycle, followed by olaratumab maintenance versus doxorubicin alone. And at the time of failure, olaratumab as a mono agent. And what was seen in the overall survival was just under a year overall survival in patients that got the combination but not the patients that got it sequentially. DR LOVE: And, of course, the thing that was also seen that was a little perplexing, and it’s been seen with a number of agents in different kinds of tumors, was that the progression-free survival advantage was much less impressive. DR VAN TINE: So there was a 2-month difference that was not statistically significant. And what’s being hinted at is maybe we’re altering the ability of sarcoma to spread by altering the microenvironment. And so the reason people may live longer is they may not be as fit to metastasize. DR LOVE: Hmm. That’s interesting. And it was interesting, the paper was published this summer. The editorial that was written, which was written by Dr Van de Graff — let me see, am I saying that right? — from the UK, kind of concludes that this is promising and they look forward to the ANNOUNCE trial, which I guess is the Phase III study. It doesn’t talk anything about the idea of actually using it based on these data. And then boom, the FDA approved it. DR VAN TINE: Yes. I think the FDA approved it contingently based on a year overall survival. Because I think one of the things that has perplexed all the investigators is our ability to explain a year overall survival in a small randomized Phase II. Because it was randomized. And I think we’ve analyzed this trial every which way Sunday and can’t come up with a really good reason for why 1 arm did really dramatically a year better. A year better is the first time we’ve — the overall survival seen with eribulin is, what, maybe 8, 10 months in the liposarcoma population, but only in liposarcoma. This was a mixed histology trial. DR LOVE: In what situations do you think you would use olaratumab? I mean, I guess the other option would be doxorubicin ifosfamide, right? DR VAN TINE: Or just doxorubicin. DR LOVE: Doxorubicin alone. Yes. Okay. So how do you sort that out? DR VAN TINE: So I think this gets easier — a little bit easier, given the tolerability of olaratumab, giving single-agent doxorubicin by itself to me now doesn’t make a lot of sense. And so at least as a treating sarcoma doctor, I think it now just becomes a question of doxorubicin/ifosfamide versus doxorubicin olaratumab. And so it’s AI versus AO. And so if you look at the patients, I think the first question is, do you need a response? And do you need a response now, or are you trying to cure the patient? I think this is a very, very small subset of patients where at least I personally will be picking up ifosfamide. I think for the standard metastatic noncurable case, doxorubicin with olaratumab is going to be my personal standard of care. I think it’s going to be a little reflective of what center you’re at and how dedicated that center is to ifosfamide in the first place. Because a lot of centers are saying this wasn’t compared to doxorubicin/ifosfamide — it was just compared to doxorubicin. But that was a lot of centers’ standards of care, given how difficult ifosfamide is. |