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Imatinib-resistant GIST: Sutent extends overall survival

An investigational new drug Sutent ( Sunitinib ) more than doubled survival and significantly reduced tumor growth and spread in patients with Imatinib-resistant gastrointestinal stromal tumors ( GIST ).

Encouraging Phase II results also were observed in other tumor types, including metastatic renal cell carcinoma ( mRCC ), metastatic breast cancer and neuroendocrine tumors.

Sunitinib is a tyrosine kinase inhibitor.

GIST studies

Results from a double-blind Phase III study of more than 300 GIST patients resistant to or intolerant of the standard treatment Gleevec ( Imatinib ) showed Sutent significantly prolonged the time to tumor progression ( 6.3 months on Sutent vs. 1.5 months for controls ) and reduced the risk of death by approximately 50 percent compared to placebo.

In addition, long-term follow-up data from the Phase I/II GIST study that served as the basis for the larger Phase III trial demonstrated that Sutent extended overall survival to nearly 20 months in patients whose cancer had progressed despite treatment with other standard therapies.
In addition, the median time to tumor progression in this study was 7.8 months for all patients, with some specific subtypes of patients benefiting even more dramatically than would be expected with Gleevec.

" These results substantiate the concept that multi-targeted molecular therapy can overcome resistance to other targeted drugs in cancer," said George Demetri of Harvard University's Dana-Farber Cancer Institute in Boston, the lead investigator on the trial for GIST. " We think that Sutent may have a broad spectrum of activity for many different forms of cancer beyond what we have seen in patients with GIST. We believe that Sutent is an important step forward in cancer therapy."

Metastatic renal cell carcinoma

Data from two Phase II studies showed patients with resistant renal cell, or kidney, tumors who received Sutent experienced high response rates and delayed tumor progression.

Results from a 63-patient trial showed 40 percent of patients responded to treatment with Sutent as measured by standard response criteria.
Tumors did not progress for more than three months in an additional 28 percent of patients, indicating that 68 percent of patients benefited from Sutent treatment.
In addition, the average time to tumor progression for patients in this study was 8.7 months, and the median overall survival was 16.4 months.

A second Phase II study of 106 patients demonstrated an objective response rate of 39 percent in patients treated with Sutent.
In addition, 23 percent of patients experienced tumor stabilization.
Taken together, a total of 62 percent of patients benefited from treatment with Sutent.

" Results from these two studies suggest that Sutent has substantial anti-tumor activity in metastatic renal cell carcinoma as second-line therapy and form the basis for the launch of a large-scale phase III program to determine the potential benefits of Sutent in earlier stage disease, " said lead study investigator Robert Motzer, at Memorial Sloan-Kettering Cancer Center. " These studies also contribute to an emerging body of data indicating that agents simultaneously targeting multiple receptors will provide new options for renal cell patients. "

The most commonly reported adverse events in Sutent clinical trials were generally mild to moderate in severity and reversible upon discontinuation of treatment.
The most common severe adverse events included fatigue, myelosuppresion and gastrointestinal upset ( diarrhea, nausea and vomiting ).
The complete adverse event profile of Sunitinib is not yet known.

Sutent has not yet been approved by the U.S. Food and Drug Administration ( FDA ) or other global regulatory agencies.

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005