Pharmacotherapy for liposarcoma: current state of the art and emerging systemic treatments

ABSTRACT

Introduction: Liposarcomas are a heterogeneous group of soft tissue tumors that arise from adipose tissue and are one of the most common soft tissue sarcomas found in adults. Liposarcomas are subclassified into four subtypes with distinct histologic and biologic features that influence their treatment and management.

Areas covered: This manuscript reviews the key clinicopathologic and cytogenic characteristics of the liposarcoma histologic subtypes and summarizes the results of recent clinical trials, treatment options, and future directions in the pharmacotherapy for the management of liposarcoma.

Expert opinion: Despite significant advancements in the management of this disease, the treatment of liposarcoma continues to be a challenge. Surgical resection remains the mainstay of treatment for localized disease; however, use of systemic therapies in conjunction with surgery may be considered in patients where tumor shrinkage could reduce surgical morbidity and in patients with high-risk of micrometastatic disease. Anthracycline-based chemotherapy regimens remain the standard first-line treatment for unresectable/metastatic liposarcoma. Trabectedin and eribulin are currently the two most promising and evidenced-based second-line treatment options for liposarcomas. However, multiple clinical trials dedicated to patients with liposarcoma evaluating novel targeted agents are ongoing. Every effort should be made to enroll patients with liposarcoma into histotype-specific clinical trials.

KEYWORDS:

• Cytotoxic Chemotherapy
• liposarcoma
• myxoid/round cell
• pleomorphic
• targeted therapy
• well-/dedifferentiated

Article highlights

• Patients with liposarcomas should be managed by a multidisciplinary cancer team specialized in the management of soft tissue sarcomas

• Surgical resection is the mainstay of treatment for localized liposarcomas, however use of systemic therapies in conjunction with surgery may be considered in select patients

• Anthracycline-based chemotherapy regimens are the standard first-line treatment for unresectable/metastatic liposarcoma

• Trabectedin and eribulin are currently approved as second-line treatment options for unresectable/metastatic liposarcoma

• Promising histology-driven targeted therapy are being evaluated with MDM2 inhibitors and CDK4/6 inhibitors for ALT/WDL and DDL, XPO1 inhibitors for DDL, PPARγ agonists for MRCL, NY-ESO-1^c259TCR for MRCL, and immune check-point inhibitors for DDL

• Every effort should be made to enroll patients with liposarcoma into histotype-specific clinical trials

This box summarizes key points contained in the article.

Declaration of interest

A. Gronchi declares having received grants from PharmaMar in addition to honoraria for lecturing and educational courses as well as compensation for advisory board participation from Novartis, Pfizer Inc, Bayer Healthcare, Eli Lilly and Company, PharmaMar and Nanobiotix. Furthermore, GG Baldi has received honoraria for lecturing and educational courses as well as travel grants from Eli Lilly and Company as well as compensation for advisory board participation and travel grant support from PharmaMar. Finally, GG Baldi has received compensation for advisory board participation from Eisai. The authors have no other 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 apart from those disclosed.

Referee disclosures

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

Additional information

Funding

This manuscript has not been funded.