Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma

Cancer. 2017 Dec 1;123(23):4640-4647. doi: 10.1002/cncr.30926. Epub 2017 Aug 18.

Abstract

Background: This phase 2, single-arm, multicenter study was designed to determine the treatment activity and safety of single-agent pazopanib in patients with unresectable or metastatic liposarcoma.

Methods: Eligible patients had high-grade or intermediate-grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor. Patients received oral pazopanib 800 mg once daily for 28-day cycles. Tumor response was evaluated by local radiology assessments every 3 cycles. The primary endpoint was the progression-free rate (PFR) at 12 weeks (PFR12).

Results: Forty-one patients were enrolled. The PFR12 was 68.3% (95% confidence interval [CI], 51.9%-81.9%), which was significantly greater than the null hypothesis value of 40% (P = .0002). At 24 weeks, 39% of patients (95% CI, 24.2%-55.5%) remained progression free, and 44% experienced tumor control (partial response or stable disease). The median progression-free survival was 4.4 months (95% CI, 3.2-6.5 months), and the median overall survival was 12.6 months (95% CI, 8.5-16.2 months). The most common adverse events overall were nausea (39%), hypertension (36.6%), diarrhea (34.1%), and fatigue (29.3%), which were typically less than grade 3. There were 5 deaths on study (12.2%), 3 of which were from possible complications of therapy.

Conclusions: The current study provides evidence of potential activity of pazopanib in the liposarcoma subset of patients with soft tissue sarcoma that was specifically excluded from the phase 3 PALETTE trial of other soft tissue sarcoma types. Cancer 2017;123:4640-4647. © 2017 American Cancer Society.

Keywords: activity; liposarcoma; pazopanib; phase 2; soft tissue sarcoma.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Indazoles
  • Liposarcoma / drug therapy*
  • Liposarcoma / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prospective Studies
  • Pyrimidines / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Survival Rate
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • pazopanib