Richard Riedel, MD
There is a limited number of effective therapies for patients with uterine sarcomas, notably due to trouble accruing for clinical trials, disappointing data, and the rarity of the disease, explained Richard Riedel, MD.
For example, the phase III GOG-0277 trial was designed to evaluate adjuvant chemotherapy with gemcitabine and docetaxel (NCT01533207) followed by doxorubicin or observation in patients with high-risk uterine leiomyosarcoma previously removed by surgery. However, the trial was closed due to low enrollment.
Surgery remains the standard therapeutic option, said Riedel, an associate professor at Duke Cancer Institute; however, immunotherapy studies, while not promising thus far, are ongoing in an effort to have improved options.
In a phase II study, nivolumab (Opdivo) was evaluated in patients with advanced uterine leiomyosarcoma. Though designed to be a two-stage study, 0 of 12 patients enrolled in the first stage had a response, and the median progression-free survival (PFS) was 1.8 months.1
Therefore, the second stage was closed.
However, findings from the phase II ALLIANCE A091401 trial demonstrated a benefit with the immunotherapy combination of nivolumab and ipilimumab (Yervoy) in patients with heavily pretreated, unselected, metastatic sarcoma. Data showed that there was an objective response rate of 16% (90% CI, 7-29), and responses were observed in uterine sarcoma.2
The FDA has approved a handful of targeted therapies for sarcomas, some of which include uterine sarcomas. For example, in October 2016, the FDA approved the PDGFRα antagonist olaratumab (Lartruvo) in combination with doxorubicin for the treatment of patients with advanced soft tissue sarcomas, including uterine leiomyosarcoma, for which a doxorubicin containing regimen would be appropriate.
In 2012, the FDA approved pazopanib (Votrient) for the treatment of patients with advanced soft tissue sarcoma who have previously received chemotherapy.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Ovarian Cancer, Reidel discussed the presentation and standard management of uterine sarcomas, the potential role of immunotherapy and targeted agents, and the challenges he hopes to overcome in the landscape in the near future.
OncLive: What is the incidence of uterine sarcomas?
: Uterine sarcomas are extremely uncommon; they represent less than 5% of all uterine cancers. Even within that heading, there are a number of different subtypes, including adenosarcoma, endometrial stromal sarcomas of both low and high grade, perivascular epithelioid cell differentiation (PEC)omas, and undifferentiated uterine sarcomas and leiomyosarcomas. Despite the heading of uterine sarcomas, it really represents a number of different histologic subtypes with very clinical behaviors.
The treatment is evolving; surgery is still the mainstay for localized disease, radiation therapy will be used for local control. Chemotherapy can be considered, but in my opinion the data are not as robust as we would like. While there have been some encouraging data for using different regimens in different subtypes, such as gemcitabine and docetaxel for uterine leiomyosarcomas, a prospective study failed to accrue. As a result, it is not clear whether we will have a definitive answer as to whether adjuvant chemotherapy benefits that population.