Soft Tissue Sarcoma Update, Issue 1, 2017 (Video Program)ET743-SAR-3007: Progression-free survival benefit with trabectedin versus dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy
2:57 minutes.
TRANSCRIPTION:
DR LOVE: In the Phase III trial they did see with trabectedin a progression-free survival of 4.2 months versus 1.5 for dacarbazine. Hazard rate of 0.55. What do you think about that? DR VAN TINE: So I think that is the analysis that actually got the final approval for the patients that actually were treated in the trial. First off, you have to realize that dacarbazine is not either a placebo or an inactive drug. And, in fact, there’s unusual activity of dacarbazine in, say, uterine leiomyosarcoma, which is included in the trial. And so there are some patients with uterine leiomyosarcoma where this is described as a very good match. There are some people that were on that for almost a year. And that’s actually really good in soft tissue sarcoma. But the difference shows that we have a very active agent. And so, because of that, even though when you go to the overall survival, it’s a very complicated discussion to get into. And so what you have to realize is most of the enrollments for this trial were third line at sarcoma centers. And so you have had doxorubicin or doxorubicin and ifosfamide and then potentially a second-line agent. And then you go on to a randomization of either dacarbazine or trabectedin. And I think what you’re seeing there is a potential selection for patients overall that are going to do a little bit better because they can get to a sarcoma center for third-line therapy. DR LOVE: The bottom line is, they didn’t see a benefit in terms of survival. Although the hazard ratio was 0.87, but it wasn’t statistically significant. But the other thing was they picked out leiomyosarcoma and liposarcoma. But there’s a bunch of other things that were looked at, but I guess those were the 2 histologies that were allowed into the trial. It looks like both had a benefit. DR VAN TINE: Yes. So in the overall and final analysis of PFS it trended toward trabectedin being more active more dacarbazine. And in that, and I think, given the worldwide data that’s available on the drug, the FDA not only looked at this trial, which was at least positive for PFS, but the worldwide experience that allowed FDA approval of trabectedin. DR LOVE: So what about using trabectedin in sarcomas other than leiomyosarcoma and liposarcoma? DR VAN TINE: So if you look at the NCCN Guidelines, it’s actually for soft tissue sarcoma. And I wasn’t really pigeon holed, because if you look at how this drug is used, it is actually a good sarcoma drug. It’s basically a DNA minor groove binder with a lot of activity. And so I think, especially, as you can see, you can now reference the nice papers the French have put out by histology, or it seems to be more or less active. There is a utility of this drug beyond just where this trial was done, because this trial was limited because the bar was set so high initially. |