Suzanne George, MD, director of Clinical Research, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and an associate professor of medicine, Harvard Medical School, discusses the importance of collaboration in the treatment of patients with uterine sarcoma.

Uterine sarcoma is a rare tumor that can be treated by many different modalities, explains George. As such, collaboration is key capitalizing on every specialist’s strength to bring the best treatments to patients. Leiomyosarcoma cannot be cured by chemotherapy alone, but there are scenarios in which chemotherapy can play a significant role in controlling the disease and helping to improve quality of life, says George. As a field, there needs to be more of a focus on balancing survival with quality of life through collaborative efforts.

Additionally, more research needs to be done on the fundamentals of biology to discover potential susceptibilities and vulnerabilities of the tumor. Naturally, science will progress in that regard, but it is up to physicians to bring this to the patients, George concludes.

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Dr. George on the Importance of Collaboration in the Treatment of Uterine Sarcomas

Suzanne George, MD, director of Clinical Research, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and an associate professor of Medicine, Harvard Medical School, discusses ongoing trials in soft tissue sarcoma (STS).

There are several ongoing trials in STS, including in leiomyosarcoma. Although the phase III ANNOUNCE trial with olaratumab (Lartruvo) and doxorubicin failed to confirm a clinical benefit in patients with advanced or metastatic STS compared with the use of doxorubicin alone, ongoing trials with olaratumab in combination with other chemotherapies are also being explored, says George.

In leiomyosarcoma, several trials with targeted therapies are also underway; however, the challenge with this approach is that physicians do not yet have a singular molecular driver for which to target, says George. Nonetheless, there are some biologic pathways that are thought to be potential vulnerabilities, including the PI3K pathway, and potentially, the mTOR pathway. Immunotherapy is another area of interest, although the majority of studies conducted to date have not demonstrated significant responses.

Dr. George Discusses Ongoing Trials in Soft Tissue Sarcoma

Suzanne George, MD, assistant professor of medicine, Harvard Medical School, clinical director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, discusses the need for biomarkers in the treatment of uterine leiomyosarcoma.

Biomarkers can be most useful in this space, George says, if they can aid in early preoperative detection. Additionally, pazopanib (Votrient) has demonstrated encouraging data in soft tissue sarcomas, subsets of leiomyosarcomas, and subsets of uterine leiomyosarcomas. However, the challenge with this drug is that it is a multikinase inhibitor. In uterine leiomyosarcoma, researchers have not yet identified a targetable mutation or pathway. As a result, it becomes difficult to determine which patients are more likely to respond to this treatment.

Moreover, George adds that in the oncology field as a whole, research needs to better understand the mechanisms of response and resistance to immunotherapy. In sarcomas in general, response rates to immunotherapy are low, but there are occasional reports of dramatic responses to this type of treatment. A distinct biomarker will help identify these patients, George concludes.

Suzanne George, MD, assistant professor of Medicine, Harvard Medical School, clinical director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, discusses the need for biomarkers in the treatment of uterine leiomyosarcoma.

Dr. George Discusses Need for Biomarkers in Uterine Leiomyosarcoma

Suzanne George, MD, assistant professor of Medicine, Harvard Medical School, clinical director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, discusses improving methods of diagnosis for women with uterine leiomyosarcoma.

There are several reasons why preoperative diagnosis is challenging, says George. In contrast with endometrial carcinoma which starts in the lining of the uterus, uterine leiomyosarcoma starts in the wall of the uterus. Sometimes endometrial biopsies can identify a uterine leiomyosarcoma, but they are not reliable because leiomyosarcoma resides outside of the parameters of the biopsy, she explains.

Novel diagnostic imaging or optimization of MRIs are being explored as potential alternatives. Others have looked at various blood tests to see whether a combination of MRI and blood tests may be more effective, explains George. To date, none of these methods are ready to be translated to clinical practice.

In women who go to hysterectomy for symptomatic fibroids, the risk of a leiomyosarcoma being identified is estimated to range from 1 in 300 to 1 in 500. Therefore, physicians need to find better methods for identifying those patients who are at high risk and improve collaboration within the field in order to offer the best care possible to patients.

Dr. George on Improving Methods of Diagnosis for Uterine Leiomyosarcoma

Suzanne George, MD, assistant professor of Medicine, Harvard Medical School, clinical director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, discusses the evolving treatment paradigm for patients with uterine leiomyosarcoma.

Uterine sarcomas are extremely rare, George says, accounting for approximately 3% of uterine cancers. Due to their low incidence rates, it is difficult to detect uterine sarcomas in their early stages. Recent studies suggest that chemotherapy regimens with docetaxel, gemcitabine, or anthracycline have activity in these patients. Each of these drugs has similar efficacy, and George says that is important for patients to understand that they have multiple treatment options available to them.

With the advent of olaratumab (Lartruvo), a novel PDGF antibody, and its approval in the United States and Europe, the paradigm has expanded even further. The addition of olaratumab to doxorubicin resulted in an overall survival advantage when compared with doxorubicin alone in patients with metastatic soft tissue sarcoma, including those with leiomyosarcoma.

A confirmatory phase III trial is currently underway, according to George, who added that olaratumab is also being evaluated in combination with other chemotherapies to better understand how this agent might further be used in the general treatment of patients with soft tissue sarcomas and in the subset of patients with uterine sarcomas.

Suzanne George, MD, assistant professor of Medicine, Harvard Medical School, clinical director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, discusses the current treatment for patients with uterine leiomyosarcoma.

Dr. George Discusses Treatment of Uterine Leiomyosarcoma

Suzanne George, MD, assistant professor of Medicine, Harvard Medical School, clinical director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, discusses a study exploring the efficacy of a PD-1 inhibitor in patients with uterine leiomyosarcoma.

Recently published research was comprised of a collaborative effort between the sarcoma and genomics team at Dana-Farber Cancer Institute, which included a patient who achieved an exceptional response to the PD-1 inhibitor pembrolizumab (Keytruda). The patient received pembrolizumab as first-line therapy for metastatic recurrent uterine leiomyosarcoma, and had a dramatic response to the agent in multiple sites of disease—with the exception of a single site.

Researchers were ultimately able to resect that resistance site of disease, she adds. Tissue samples were gathered from her baseline tumor, which had a dramatic response, and the resistant tumor in an attempt to determine the factors for resistance. These 2 differences may help researchers understand why it became resistant.

Suzanne George, MD

Articles

Dr. George on the Importance of Collaboration in the Treatment of Uterine Sarcomas

Dr. George Discusses Ongoing Trials in Soft Tissue Sarcoma

Dr. George Discusses Need for Biomarkers in Uterine Leiomyosarcoma

Dr. George on Improving Methods of Diagnosis for Uterine Leiomyosarcoma

Dr. George Discusses Treatment of Uterine Leiomyosarcoma

Dr. George on Efficacy With PD-1 Inhibitor in Uterine Leiomyosarcoma