CHICAGO–Patients with metastatic soft tissue sarcoma (STS) who had previously received anthracycline had a threefold increase in progression-free survival (PFS) when treated with pazopanib vs. placebo, according to results of the randomized Phase 3 PALETTE trial reported at American Society of Clinical Oncology’s 2011 Annual Meeting.

Winette T.A. van der Graaf, of Radboud University, Nijmegen Medical Centre, Nijmegen, Netherlands, presenting the results of the EORTC STBSG Global Network Study, reported an increase in median PFS of 13 weeks with pazopanib vs. placebo. Pazopanib, a multitargeted angiogenesis inhibitor, has demonstrated single-agent activity in patients with advanced STS.

In this study, the efficacy and safety of pazopanib vs. placebo as second or later line treatment were evaluated in patients with metastatic STS in a multi-center, international, double-blind, placebo-controlled trial.

Patients ≥18 years of age with angiogenesis inhibitor-naïve, histologically proved, metastatic STS, who failed at least one anthracycline-containing regimen, could enter the study. Eligibility criteria included ≥1 measurable baseline lesion (per RECIST v1.0), WHO PS 0-1, adequate bone marrow, coagulation, hepatic and renal function, no poorly controlled hypertension, no bleeding diathesis, and no CNS involvement. Patients were randomized 2:1 to receive either pazopanib 800mg once daily or placebo until tumor progression, unacceptable toxicity, death, or discontinuation at the request of the patient.

A total of 369 randomized patients (246 pazopanib; 123 placebo) participated in the study. Median age was 51.9 years in the placebo group and 56.7 years in the pazopanib group. At a median follow-up of 15 months, the primary endpoint of PFS per independent review was significantly prolonged with pazopanib (median: 4.6 vs. 1.5 months; HR 0.31 [0.24–0.40]; P<0.0001). The interim analysis for overall survival shows a statistically nonsignificant improvement of pazopanib vs. placebo (median: 11.9 vs 10.4 months; HR 0.83 [0.62-1.09]; P=0.1782).

Best overall response based on independent review is 14 partial responses in the pazopanib group (vs. none in the placebo group) and 164 patients with stable disease (vs. 47 in the placebo group).

Dr. van der Graaf noted that with adequate monitoring and timely interventions, adverse events are manageable. The primary therapy Grade 3/4 toxicities in the pazopanib vs. placebo arm, respectively, were fatigue (13.4%, 6%), hypertension (7%, nil), anorexia (6%, nil), and diarrhea (5%, 1%). Thromboembolic events (Grade 3-5) were 3% in the pazopanib group and 2% in the placebo group. Median relative dose intensity of pazopanib was 98.6%. Eight patients died; one death (liver and kidney failure) was related to treatment with pazopanib.

Final OS analysis is anticipated later this year. The study was conducted by EORTC and GlaxoSmithKline in collaboration with 72 sarcoma centers worldwide.