A subgroup analysis of the phase III SAR-3007 trial demonstrating the efficacy of trabectedin (Yondelis) in patients with advanced uterine leiomyosarcoma bodes well for the malignancy's armamentarium, according to Martee L. Hensley, MD.
In the overall SAR-3007 study population, patients with advanced liposarcoma or leiomyosarcoma who received trabectedin had a significantly improved median PFS of 4.2 months versus 1.5 months for dacarbazine (HR, 0.55;P<.001). Overall survival (OS) was 13.7 months with trabectedin versus 13.1 months with dacarbazine (HR, 0.93;P= .49).
Hensley, a medical oncologist at Memorial Sloan Kettering Cancer Center, presented data at the 2016 Society of Gynecologic Oncology Annual Meeting showing that in patients enrolled in SAR-3007 with uterine leiomyosarcoma, the median PFS was 4.0 months with trabectedin versus 1.5 months with dacarbazine. Consistent with the overall population, there was not a significant improvement in OS.2
In an interview withTargeted Oncology, Hensley explains the impact of the study and what lies ahead for the treatment paradigm of uterine leiomyosarcoma.
Can you tell us about the phase III SAR-3007 trial looking at trabectedin versus dacarbazine?
This was a randomized trial of trabectedin versus dacarbazine in patients with leiomyosarcoma or liposarcoma, and they were randomly assigned 2:1 to receive either trabectedin or dacarbazine. The primary endpoint of the study was OS, and second endpoints included response rate and PFS.
At the 2016 Society of Gynecologic Oncology Annual Meeting, I presented data from the uterine leiomyosarcoma subgroup of that larger study. In that uterine leiomyosarcoma subgroup, trabectedin was associated with a progression-free survival of approximately 4.2 months compared with about 1.5 months for patients who had been assigned to dacarbazine.
Although there was no difference in OS, the duration of disease control, or clinical benefit as some people like to refer to it, was quite sustained in patients in the trabectedin arm.
With that improved clinical control, would that bode well for trabectedin in uterine leiomyosarcoma?
I think it could. I would consider trabectedin a new drug in the armamentarium for trying to help patients live longer with advanced cancer. In uterine leiomyosarcoma, there are currently no interventions that lead to long-term cures.
However, if you can achieve disease control with a drug or a certain set of drugs for some months, then you can have other drugs to administer in later lines of therapy. We hope that we can provide prolonged disease control for patients using a series of agents, and trabectedin would be a new one in a list that has not been very long to date, but is, fortunately, growing longer.
Could trabectedin be a gateway to other treatments within the realm of uterine leiomyosarcoma?
Perhaps. If you have disease control with first-, second-, or third-line therapy and you're still alive and are well enough to get additional therapies, there's always the hope that there will be new drugs in the pipeline that will show activity in leiomyosarcoma.
If the question was more about whether or not trabectedin was likely to be added to current available therapies to be looked at in combinations, I think that remains to be seen. It is a cytotoxic drug, and is probably not that easy to combine with other cytotoxic drugs with the hopes of augmenting response rates or disease control.
Where does trabectedin fit into the treatment paradigm of uterine leiomyosarcoma?
It is helping in later lines of therapy. Gemcitabine and docetaxel is a regimen that has been around for some time. It achieves objective response rates of over 30% in most patients with uterine leiomyosarcoma. For patients with a high-disease burden where you really need to shrink the cancerthat is a very reasonable regimen, as is doxorubicin—which has been around for decades, with or without ifosfamide.
Trabectedin is coming onto the treatment paradigm somewhere around third line for patients who have clearly already failed an anthracycline, such as doxorubicin. That is the FDA approval for the drug, and all of the patients in the study had to have prior anthracycline therapy.
Trabectedin would be considered around third line, or some people might consider it fourth line because we also have pazopanib (Votrient), which is an oral antiangiogenesis multikinase inhibitor that is also approved for the treatment of advanced sarcomas.
Trabectedin was approved as of October 2015, so it is commercially available for doctors to use. In general, uterine leiomyosarcoma and sarcomas are relatively rare diseases. Not everyone has a lot of experience taking care of those patients or experience using drugs that have this relatively narrow indication.
It is useful to get the information out there when new drugs become available, and then helpful to show people how to use themand use them safely.
What do you hope community oncologists will take away from this study?
I hope they will see that progress is being made in uterine leiomyosarcomas. When I started working in this field, there were very few studies and few drugs for uterine leiomyosarcomas. We have made a lot of progress.
I hope they see that clinical research does drive the field forward in rare tumors and, specifically, in uterine leiomyosarcomas. When facing a patient with uterine leiomyosarcoma, know that there is a list of agents to think about as treatments. Have some idea on how to sequence those treatments. Finally, know that there are experts to go to for advice about to best take care of these women.