Doxorubicin-Trabectedin Impresses in Leiomyosarcoma

The combination of doxorubicin and trabectedin (Yondelis) continued to show encouraging activity as first-line treatment of patients with metastatic or unresectable leiomyosarcoma (LMS), according to results from the phase III LMS-04 trial presented at the recent European Society for Medical Oncology (ESMO) virtual meeting.

In this exclusive MedPage Today video, Mark Agulnik, MD, sarcoma section chief at the City of Hope Comprehensive Cancer Center in Duarte, California, explains the relevance of the study to his patients.

Following is a transcript of his remarks:

I’m Dr. Mark Agulnik. I am a professor at City of Hope, and I am the sarcoma section chief. So this is the LMS-04 study, which is a randomized, multicenter, phase III study comparing doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin in non-progressive patients as first-line therapy, in patients with metastatic or unresectable leiomyosarcoma. It is a French Sarcoma Group study that was presented by Patricia Pautier.

The relevance of this one is, I think that over the last decade, we’ve seen a number of phase III clinical trials as first line for patients with soft tissue sarcomas, all of them trying to challenge the effects of single-agent doxorubicin and all of them coming up short. So over the years we’ve always looked to see whether or not we could approve upon first-line agents.

And so this was a fascinating trial because it is looking for a very unique population, the patients with metastatic or unresectable leiomyosarcoma. And finally, we do have an agent that in addition to Adriamycin [doxorubicin] is able to improve outcomes for our patients, and something that we really do need to consider for a select group of our soft tissue sarcoma patients moving forward.

Being a phase III trial, the trial did show that there was an improvement, and a significant improvement, in progression-free survival in this metastatic leiomyosarcoma population. But it does come at a cost and the cost is the additional expected manageable toxicities, but patients don’t walk away feeling as well as they do when they’re on Adriamycin alone. And so for the right patient, we really have to see whether or not they want to increase their toxicities in order to improve a progression-free survival. And there was an overall response rate benefit, so for a patient who has symptomatic disease, this would be beneficial as well. And there’s also an overall survival benefit. And so for the right patient, if you could withstand the added toxicities, it certainly would be beneficial for them.