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Novel Strategies Emerging in Uterine Sarcomas

Gina Columbus @ginacolumbusonc
Published: Wednesday, Jan 16, 2019

Suzanne George, MD

Suzanne George, MD

While chemotherapeutic approaches are available for patients with uterine sarcomas, research is moving in the direction of novel combinations, biomarkers, and collaboration, explained Suzanne George, MD.

Regimens that include gemcitabine plus docetaxel, and agents such as olaratumab (Lartruvo), trabectedin (Yondelis) and pazopanib (Votrient) have been a staple in treatment approaches. Now, some of these agents are being evaluated in combination, while the PI3K and mTOR pathways are becoming of interest.

“As a field, we need to figure out how to be better at proactively identifying patients at higher risk for an underlying malignancy, and how to work collaboratively as a field in order to bring the best care to our patients,” said George, director of Clinical Research, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and an associate professor of Medicine, Harvard Medical School.

In an interview during the 2018 OncLive® State of the Science Summit™ on Ovarian Cancer, George highlighted the available therapies for patients with uterine sarcomas and what novel options are on the horizon.

OncLive: What is the current state of uterine sarcoma management?

George: [At the State of the Science Summit™] I discussed systemic therapies in uterine leiomyosarcoma, specifically the role of chemotherapy in patients with advanced or metastatic disease. A key point is that there is an increasing number of systemic options available for patients with this disease, with a number of new approvals over the last several years and some promising agents that are currently under development.

I was very appreciative to be invited to participate in this talk [at this meeting]; I know that the program is primarily a gynecologic oncology talk and program, and I spoke on sarcomas of the uterus. Uterine sarcomas are uncommon; they represent a collectively 3% or less of all uterine cancers, and uterine malignancies are challenging because it’s a group of diseases; leiomyosarcomas is one of the subtypes of uterine sarcomas.

For women who are diagnosed with these rare tumors, they can enter the health system in so many different ways—through gynecology, through gynecologic oncology, through medical oncology that’s part of gynecology, or through a soft tissue sarcoma medical oncologist that is not part of gynecology. We have this group of women who have rare diseases with care that can be fragmented because they can enter the system in so many different ways.

As a field, there is a tremendous opportunity for collaboration between gynecologic oncology and sarcoma medical oncology to build bridges around what we understand—around what we need to learn, so that we can come together as a community, fundamentally, with patients at the center.

Could you expand on some of the available options?

Recent studies have suggested that gemcitabine-/docetaxel-based regimens, as well as anthracycline-based regimens, have activity in this disease. It is not about which one is better, per se, but women should know that there are multiple options available to them. [For example] olaratumab, a novel PDGFR-α antibody, was approved over the last couple of years in both the United States and in Europe. Again, it really highlights the importance of collaboration and communication in this field.

Olaratumab, when used with doxorubicin, demonstrated an overall survival (OS) advantage when compared with doxorubicin alone in patients with metastatic soft tissue sarcoma, including leiomyosarcoma. This improvement in OS led to the approval in the commercial availability of the drug, but it also comes with the requirement of a confirmatory phase III trial, which is currently underway. The study has completed its accrual and we are just waiting for the readout; it is something we will really be looking forward to. Olaratumab is also being studied in combination with other chemotherapies, just to see how we are going to exactly use this agent in soft tissue sarcoma, but also in the subset of women with uterine sarcomas.

The diagnosis of a uterine leiomyosarcoma can be challenging. Are experts in the field working on new methods?

That is such a critically important question. There are many reasons that it is difficult to diagnose this tumor preoperatively. One, it is in contrast to endometrial carcinoma, which starts in the lining of the uterus; leiomyosarcoma starts in the wall of the uterus, so even though sometimes endometrial biopsies are performed [and] you can sometimes make the diagnosis, it’s just not a completely reliable strategy. This is because the tumors that are in the wall are not in the lining—it’s outside where the biopsy reaches.

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