Pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma

ABSTRACT

Introduction: Liposarcomas (LPS) are a heterogeneous group of adipocytic soft tissue sarcomas with limited treatment options in the advanced/metastatic setting. Pazopanib is a multi-target tyrosine kinase inhibitor (TKI) with anti-angiogenic and antitumorigenic properties. Whilst targeted agents including TKIs have been extensively studied in other solid tumors and the sarcoma subtype gastrointestinal stromal tumor (GIST), we currently lack effective treatments for the liposarcoma subtype. Several phase II and III studies of oral TKIs in soft tissue sarcomas have excluded liposarcoma because of a reported lack of activity following the EORTC 62043 study.

Areas: We review the use of pazopanib in advanced intermediate and high-grade liposarcomas where complete surgical resection is not possible.

Expert opinion: The current clinical and pharmacological data demonstrate the efficacy of pazopanib in soft tissue sarcomas, but new data suggest that anti-angiogenic agents may have limited activity in liposarcoma. Anti-angiogenic TKIs are generally well tolerated and liposarcomas vary in their response to systemic chemotherapy; hence, there is a role for further exploration of the efficacy of this treatment amongst the histological subtypes of liposarcoma. This affords further understanding of biomarkers which may be associated with response to pazopanib and other anti-angiogenic TKI treatments.

Trial registration: ClinicalTrials.gov identifier: NCT03096912.

Trial registration: ClinicalTrials.gov identifier: NCT02846987.

Trial registration: ClinicalTrials.gov identifier: NCT01692496.

Trial registration: ClinicalTrials.gov identifier: NCT01532687.

KEYWORDS:

• Liposarcomas
• Pazopanib
• tyrosine kinase inhibitor
• soft tissue sarcomas
• angiogenesis
• targeted therapy

Article highlights

• Pazopanib is an oral multi-target tyrosine kinase inhibitor (TKI) with anti-angiogenic and anti-tumourigenic properties used in a range of soft tissue sarcomas.

• Pazopanib was deemed inactive in liposarcomas based on preliminary results of a phase II study where it did not meet the predefined criteria for accrual into the second stage of the study.

• Pazopanib was therefore excluded from the subsequent phase III study of pazopanib in soft tissue sarcomas. However, in the final analysis of the antecedent phase II study, pazopanib did meet the predefined criteria in liposarcoma, therefore the opportunity to investigate its activity in this subtype was missed.

• Pazopanib is well tolerated and demonstrates improved haematological toxicity profile compared to existing systemic anticancer treatments.

• Phase II data supporting the use of pazopanib in intermediate and high grade liposarcoma are mounting and phase III studies in selected histological subtypes are warranted.

Declaration of interest

RL Jones has received honoraria and consultation fees from Adaptimmune, Blueprint, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immunedesign, Lilly, Merck and Pharmamar. He is also a co-inventor on patent applications related to biomarkers of pazopanib response in sarcoma. P Huang is a co-inventor on patent applications related to biomarkers of pazopanib response in sarcoma. 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. 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.