Richard F. Riedel, MD, associate professor of medicine, Duke Cancer Institute, discusses targeted therapy options for patients with uterine sarcomas.

Pazopanib (Votrient) was FDA approved in 2012 for a broad range of soft tissue sarcomas—uterine sarcomas included. This was based off the phase III PALETTE study. While the response rates for pazopanib are low, the real benefit is seen in disease control, notes Riedel. More recently, trabectedin (Yondelis) was approved in October 2015 for leiomyosarcoma and liposarcoma. Liposarcomas are not often seen in the uterus, but leiomyosarcomas are common. That study approval was based on results from the phase III ET743-SAR-3007 trial which demonstrated an improvement in progression-free survival compared with dacarbazine, an active comparator.

Riedel concludes that researchers have made advances with those agents; most recently olaratumab (Lartruvo) was approved in 2016 to be used in combination with doxorubicin. That was based on a phase II study in which the combination showed an improvement in overall survival compared with doxorubicin alone.

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Dr. Riedel on Targeted Therapy for Uterine Sarcomas

Richard F. Riedel, MD, associate professor of medicine, Duke Cancer Institute, discusses the emerging role of immunotherapy in uterine sarcoma.

There was a phase II study that was recently published recently from Dana-Farber Cancer Institute looking at the role of nivolumab (Opdivo) in uterine leiomyosarcoma. It was designed to be a two-stage study, but in the first stage only 12 patients were enrolled, and the median progression-free survival was less than 2 months. As a result, the second stage never enrolled.

Immunotherapy in sarcoma is being investigated in a number of different histologies, including leiomyosarcomas that are not uterine specific and soft tissue sarcomas, states Riedel. In the SARC028 study, which looked at pembrolizumab (Keytruda), the response rates for leiomyosarcomas were essentially 0%. However, it was a small cohort of patients—only 9 or 10 patients were enrolled on that cohort.

In a recently published study that looked at nivolumab with or without ipilimumab (Yervoy), there were responses in both uterine and nonuterine leiomyosarcomas, states Riedel. There are ongoing expansion cohorts trying to further identify whether there is a signal there or not, says Riedel.

Dr. Riedel on the Role of Immunotherapy in Uterine Sarcoma

Richard F. Riedel, MD, associate professor of medicine, Duke Cancer Institute, discusses the rarity and characteristics of uterine sarcomas.

The presentations of the disease are varied, but one of the most common symptoms is abnormal bleeding, or what is known as menorrhagia. Riedel says this could result in an evaluation and the detection of a mass. Oftentimes, uterine sarcomas can be misdiagnosed as a uterine fibroid. It is not until the mass is removed that the cancer is actually identified.

The biggest challenge lies in the rarity of the disease. Sarcomas as a whole represent about 1% of cancers in adults, and uterine sarcomas represent about 5% of all uterine cancers. Essentially, 99% of the time, a uterine mass will be benign as opposed to sarcoma, which Riedel says can mislead physicians at times. The symptoms are also sometimes nonspecific.

Dr. Riedel Discusses the Rarity of Uterine Sarcomas

Richard F. Riedel, MD, associate professor of medicine, Duke Cancer Institute, discusses the treatment landscape of uterine sarcomas.

Uterine sarcomas are very uncommon, representing less than 5% of all uterine cancers. There are many histologic subtypes of uterine sarcomas, including adenosarcoma, endometrial stromal sarcomas, PEComas, undifferentiated uterine sarcomas, and leiomyosarcomas. Though the treatment landscape is always evolving, surgery remains a mainstay in localized disease, says Riedel. Chemotherapy can be considered, though the data are not as compelling as physicians would like.

There have been data in support of different regimens such as gemcitabine and docetaxel for uterine leiomyosarcomas, but a prospective study failed to enroll patients. Physicians are unsure whether adjuvant chemotherapy truly benefits this patient population.

Immunotherapy has an emerging role in sarcomas as a whole, states Riedel. It may not be as successful as in melanoma and lung cancer, but there are specific subtypes that may benefit. Whether or not its success will translate specifically to patients with uterine sarcomas has yet to be seen.

Richard F. Riedel, MD

Articles

Dr. Riedel on Targeted Therapy for Uterine Sarcomas

Dr. Riedel on the Role of Immunotherapy in Uterine Sarcoma

Dr. Riedel Discusses the Rarity of Uterine Sarcomas

Dr. Riedel on the Treatment Landscape of Uterine Sarcomas