Current state of the art and emerging pharmacotherapy for uterine leiomyosarcomas

ABSTRACT

Introduction: Uterine leiomyosarcomas (ULMS) account for 1% of all uterine malignancies and for 30% of all uterine sarcomas. The preoperative diagnosis of ULMS is challenging for the physicians, as the symptoms of these tumors are often vague and nonspecific. Moreover, as ULMS have an aggressive biologic behavior, affected women frequently have very poor prognosis.

Areas covered: The aim of this review is to describe the current pharmacotherapy for ULMS, including the ongoing clinical trials.

Expert opinion: Surgery is the standard treatment for patients with early-stage ULMS. In this setting, the role of adjuvant therapies is still unclear. In the case of advanced, persistent, or recurrent ULMS, chemotherapy is the standard care with the most frequently used drug being doxorubicin. As the outcomes for patients with the currently available conventional single or combined regimens are far from being satisfactory, new alternative and innovative medical compounds have or are being evaluated. Recently, pazopanib, and olaratumab, two innovative targeted drugs, have been approved by the Food and Drug Administration (FDA) for treating advanced soft-tissue sarcoma, including ULMS. However, further clinical investigations into new and innovation therapeutic options are warranted.

KEYWORDS:

• Leiomyosarcomas
• gemcitabine
• doxorubicin
• targeted therapy
• pazopanib
• olaratumab

Article highlights

• Uterine leiomyosarcomas (ULMS) account for 1% of all uterine malignancies and for 40% of all uterine sarcomas. The preoperative diagnosis of ULMS is challenging for the physicians, as the symptoms of these tumors are vague and nonspecific.

• Surgery is the standard treatment for patients with uterine-confined ULMS. The role of adjuvant therapy (in particular chemotherapy) remains still debated. In this setting, the most employed drug has been doxorubicin.

• In the case of advanced, persistent, or recurrent ULMS, chemotherapy is the standard of care. At the moment, doxorubicin is again the most widely accepted and recommended first-line treatment.

• In October 2016 the Food and Drug Administration (FDA) granted accelerated approval to olaratumab combined with doxorubicin for the treatment of women with unresectable soft tissue sarcomas not amenable to treatment with surgery or radiation, after the promising results of a phase I-IIb trial. Currently, an ongoing phase III trial (NCT02451943) is investigating the survival advantage given by this drug.

• Several regimens have shown activity as a second-line treatment for recurrent ULMS; anyway, the prognosis of these patients is very poor. The majority of trials on these drugs are uncontrolled and include heterogenous patients. Among these drugs, trabectedin is an emerging promising option.

• Overall, the results with the available conventional drugs (alone or in combination) are far from being satisfactory for treating advanced ULMS. Currently, research is focused on finding new therapeutic targets. Further prospective clinical trials are warranted to investigate new therapeutic agents, such as Aurora kinase (Aurk)-A.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.