(ChemotherapyAdvisor) – Pazopanibimproves progression-free survival (PFS) in patients with metastatic non-adipolyticsoft-tissue sarcoma and should be considered a new treatment option, investigators concluded in The Lancet online May 16.

The Phase 3 randomized study, conducted in 72institutions across 13 countries, is the first to show improvement in PFS inpatients with non-adipolytic soft-tissuesarcoma in decades, according to the European Organization for Research andTreatment of Cancer Soft Tissue and Bone Sarcoma Group and PALETTE study group. In the U.S., an estimated 11,000 new cases are diagnosed annually,making it a rare cancer.

In this trial, patients who had angiogenesis inhibitor-naïve, metastatic soft-tissuesarcoma that had progressed despite previous standard chemotherapy wererandomly assigned in a 2:1 ratio to either pazopanib 800mg once daily (n=246) or placebo (n=123); no subsequent cross-over was allowed. Those with gastrointestinal stromal tumors (GIST) andliposarcomas were excluded from the study.

MedianPFS, the primary endpoint, was 4.6 months for pazopanib vs. 1.6 months for placebo(HR 0.31; P<0.0001). Overallsurvival was 12.5 months with pazopanib vs. 10.7 months with placebo (HR 0.86; P=0.25).

Pazopanib was discontinued in 34 patients (14%)because of drug-related toxic effects. Of 8 fatal adverse events in thepazopanib group, one was multiorgan failure that might have been related tothe study drug. Overall, self-reported quality of life did not differsignificantly between the placebo and pazopanib groups, but individualcomponents such as diarrhea, nausea, and fatigue were significantly worse onpazopanib.

The mostcommon adverse events were fatigue (65% in the pazopanib group vs. 49% in theplacebo group), diarrhea (58% vs. 16%), nausea (54% vs. 28%), weightloss (48% vs. 20%), andhypertension (41% vs. 7%). Newly reportedside effects were venous thromboembolic events, pneumothorax, andcardiotoxicity.

“Pazopanib isan active drug for patients in the heterogeneous group of non-adipocyticsoft-tissue sarcomas,” the investigators reported. “After the breakthroughs ofimatinib and sunitinib for gastrointestinal stromal tumor, pazopanib is thefirst active oral agent for patients with nongastrointestinal stromal tumorsoft-tissue sarcomas and is a meaningful addition to the treatmentarmamentarium for patients with this rare group of tumors.”

An accompanying comment noted, “This was awell-designed and conducted study, that showed a 3-month improvement in theprimary outcome of progression-free survival. [But] the desired effect ofpalliative chemotherapy is that tumor shrinkage or delay of progression willimprove patients’ activity or well-being, but this effect was not definitivelyshown.”

Abstract

Clinical Trial