Systemic Therapy for Soft Tissue Sarcoma: Proposals for the Optimal Use of Pazopanib, Trabectedin, and Eribulin

Abstract

Soft tissue sarcoma (STS) is a rare tumor with more than 50 histologic subtypes. Although treatment outcomes for patients with STS have improved greatly over the past few decades owing to the adoption of a multidisciplinary approach, patients with advanced disease have a poor prognosis. The development of anticancer drugs has been directed toward improving overall survival (OS). Doxorubicin monotherapy is currently the only standard option for the first-line treatment of STS. However, there is no standard therapy for second-line and later treatment at present. Since 2012, three anticancer drugs—pazopanib, trabectedin, and eribulin—have been approved in Japan for the second-line or later treatment of patients with advanced STS of any histologic subtype. However, the chemosensitivity of STS to each of these drugs varies by histologic subtype and their safety profiles differ; thus, histologic subtype and patient characteristics must be considered when determining optimal treatment. In this article, we review data from clinical studies related to the efficacy of all three drugs, including their effect on OS, and propose optimal treatment strategies for advanced STS by histologic subtype. In addition, with regard to the safety profiles, we highlight the key issues to be considered when selecting patients for treatment with pazopanib, trabectedin, or eribulin and ensuring their appropriate use, based on our combined clinical experience as specialists in the treatment of patients with STS. The proposed treatment strategies as well as treatment precautions based on clinical experience would benefit patients by maximizing the therapeutic effects and enhancing the proper use of these drugs. Funding: Eisai Co., Ltd.

Glycogen synthase kinase 3β as a potential therapeutic target in synovial sarcoma and fibrosarcoma

“…Several potential molecular therapeutic targets have emerged recently for STSs. Unfortunately, the clinical trials that target them have shown little benefit for patients with refractory STSs, including synovial sarcoma and fibrosarcoma . This has led us to investigate whether GSK3β could be a useful target for the treatment of these sarcoma types.…”

“…More than 50 histological subtypes of STS are defined by the WHO classification, with each having a different treatment response and prognosis . As a result of the wide range of histological subtypes and occurrence at various sites, STS patients are treated by different clinical departments, which ultimately complicates a general overview of STS …”

“…Recently, several targeted agents such as pazopanib (a multi‐tyrosine kinase inhibitor) have been developed, together with a new generation of anticancer agents including trabectedin and eribulin for STSs including synovial sarcoma and fibrosarcoma. These agents improved the progression‐free and overall survival of STS patients, but showed no improvement over conventional anticancer drugs . Therefore, the discovery of new therapeutic targets is urgently required for the development of efficient, biologically based treatments against STSs …”

Calcium-Dependent Calpain Activation-Mediated Mitochondrial Dysfunction and Oxidative Stress Are Required for Cytotoxicity of Epinecidin-1 in Human Synovial Sarcoma SW982 Cells

“…Anthracycline-based regimes are the first-line therapy [3,4]. Second-line chemotherapeutic agents for synovial sarcoma include Pazopanib, Trabectedin, and Eribulin [4][5][6][7]. For metastatic cases, chemotherapy is the main treatment [2].…”

A revolution in the treatment of aggressive liposarcoma by pazopanib combined with chemotherapy- A case report

“…Therapeutic strategy for patients with LPS includes chemotherapy, radiation therapy, surgical and tissue sparing. However, the complete treatment of LPS is a challenge 6,7 . Therefore, a new strategy is required for a more effective treatment.…”