May 16, 2012 — The clinical trial showing benefit from pazopanib (Votrient) in soft tissue sarcoma, which was the basis for the drug's recent approval for this indication, was published online today in the Lancet.
The trial, known as PALLETE (Pazopanib Explored in Soft-Tissue Sarcoma), is the first phase 3 study to be conducted in nongastrointestinal stromal tumor (GIST) soft tissue sarcoma, the authors note. The study excluded patients with adipocytic soft tissue sarcomas (liposarcomas). GIST and liposarcomas each account for around 30% of all sarcomas; this study — and the recent approval — covers the remaining 40% of soft tissue sarcomas.
The trial showed that in patients who had failed on standard chemotherapy, pazopanib significantly improved progression-free survival, compared with placebo (4.6 vs 1.6 months; P < .00010). However, overall survival was not significantly different in the pazopanib and placebo groups (12.5 vs 10.7 months; P = .25).
Pazopanib is the first oral active agent for patients with non-GIST and nonadipocytic soft tissue sarcomas, and is "a meaningful addition to the treatment armamentarium for patients with this rare group of tumors," the authors report.
However, in an accompanying comment, Vivien Bramwell, MBBS, PhD, from the Tom Baker Cancer Center in Calgary, Alberta, Canada, questions whether a significant improvement in progression-free survival but not overall survival is a clinically significant benefit in advanced soft tissue sarcoma.
The standard treatment for soft tissue sarcoma is chemotherapy, and the desired effect of palliative chemotherapy is that tumor shrinkage or delay in progression will improve patients' activity or wellbeing, she explains. "This effect was not definitely shown" for pazopanib, she adds.
One of the study authors, George Demetri, MD, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts, elaborated on the use of chemotherapy in a recent interview.
When it works in sarcoma, chemotherapy shrinks the tumor, whereas targeted agents such as pazopanib do not — they arrest the tumor and stop it from growing, he told Medscape Medical News. But given the serious toxicity associated with the aggressive chemotherapy (usually an anthracycline such as doxorubicin, either alone or with ifosfamide), in patients who have a small tumor or tumors that are not causing many symptoms, arresting the disease with an oral drug with less toxicity "would be doing them a favor," he said.
In her comment, Dr. Bramwell writes that the investigators conclude that pazopanib provides a new treatment option, and asks: "There will be a demand for it, but will funding agencies be willing to, or able to, pay?"
The study was sponsored by GlaxoSmithKline, the manufacturer of pazopanib. Several of the coauthors are company employees. Dr. Demetri reports receiving consultant and research support from GlaxoSmithKline, Pfizer, Novartis, Sanofi, Ariad, Merck, Johnson & Johnson, PharmaMar, Daiichi-Sankyo, and Amgen; and serving as a consultant for ZioPharm. Dr. Bramwell reports serving on a Canadian advisory board for GlaxoSmithKline for pazopanib.
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Cite this: Pazopanib in Sarcoma: Clinically Significant Benefit? - Medscape - May 16, 2012.
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