Pazopanib Improves Progression-Free Survival in Metastatic Soft-Tissue Sarcoma

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(ChemotherapyAdvisor) – Pazopanib improves progression-free survival (PFS) in patients with metastatic non-adipolytic soft-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 72 institutions across 13 countries, is the first to show improvement in PFS in patients with non-adipolytic soft-tissue sarcoma in decades, according to the European Organization for Research and Treatment 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-tissue sarcoma that had progressed despite previous standard chemotherapy were randomly 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) and liposarcomas were excluded from the study.

Median PFS, the primary endpoint, was 4.6 months for pazopanib vs. 1.6 months for placebo (HR 0.31; P<0.0001). Overall survival 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 the pazopanib group, one was multiorgan failure that might have been related to the study drug. Overall, self-reported quality of life did not differ significantly between the placebo and pazopanib groups, but individual components such as diarrhea, nausea, and fatigue were significantly worse on pazopanib.

The most common adverse events were fatigue (65% in the pazopanib group vs. 49% in the placebo group), diarrhea (58% vs. 16%), nausea (54% vs. 28%), weight loss (48% vs. 20%), and hypertension (41% vs. 7%). Newly reported side effects were venous thromboembolic events, pneumothorax, and cardiotoxicity.

“Pazopanib is an active drug for patients in the heterogeneous group of non-adipocytic soft-tissue sarcomas,” the investigators reported. “After the breakthroughs of imatinib and sunitinib for gastrointestinal stromal tumor, pazopanib is the first active oral agent for patients with nongastrointestinal stromal tumor soft-tissue sarcomas and is a meaningful addition to the treatment armamentarium for patients with this rare group of tumors.”

An accompanying comment noted, “This was a well-designed and conducted study, that showed a 3-month improvement in the primary outcome of progression-free survival. [But] the desired effect of palliative chemotherapy is that tumor shrinkage or delay of progression will improve patients' activity or well-being, but this effect was not definitively shown.”


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