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Sunitinib appears to prolong survival in patients with GIST after imatinib failure
PARIS — Sunitinib (SU11248, Pfizer) prolongs both progression-free and overall survival in patients with progressive metastatic and/or unresectable gastrointestinal stromal tumors (GISTs) whose disease has failed to respond to the standard therapy, according to a presentation here at ECCO 13, the European Cancer Conference.
International researchers enrolled 312 patients into a phase-3, double-blind, placebo-controlled, multicenter trial. The patients had GIST whose cancer had progressed despite previous treatment with imatinib (Gleevec, Novartis). Sunitinib treatment was in a repeated six-week cycle consisting of a 50-mg capsule once daily for four weeks, followed by a two-week break.
Results from the first planned interim analysis of this trial demonstrated a fourfold increase in the average time to progression with sunitinib treatment compared with placebo. The estimated median time to progression was 6.3 months with sunitinib vs. 1.5 months for placebo. Overall survival has also been estimated to be significantly greater with sunitinib therapy, although the average overall survival point has not yet been reached in either the sunitinib or placebo treatment arm.
Overall, treatment with sunitinib was well tolerated, although fatigue, diarrhea, nausea, sore mouth and skin discoloration proved to be the most common nonhematological adverse events. Adverse events were generally mild to moderate, and no severe effects were noted during the course of the study.
“These results from our global collaborative team provide important confirmatory evidence that documents the significant efficacy and acceptable tolerability of sunitinib (SU11248) in patients with metastatic GIST whose disease was resistant to imatinib, or those who experienced unacceptable side effects from imatinib. Before sunitinib, there was no therapy of proven value for such patients, and this trial shows that sunitinib has documented benefits,” said George Demetri, MD, from the Dana-Farber Cancer Institute and Harvard Medical School.
Sunitinib inhibits a number of important tyrosine kinase enzymes to exert anti-angiogenic and antitumor effects.
The study could have a considerable effect on future treatments. “The development of sunitinib has proceeded exceptionally fast, with the first GIST patient having started the drug in 2002, and now completion of a global phase-3 clinical trial to confirm the benefits in 2005. This timeline represents the future of truly effective, targeted therapies which home in on the molecular causes of cancer. Once these targets are neutralized by effective new drugs, the benefits in terms of treating cancers such as GIST can be documented,” Demetri said. “The results of this trial will change therapy for GIST patients worldwide by introducing a new and effective agent into the physicians’ therapeutic armamentarium. We have much to learn about the patients who benefit the most from SU11248 therapy, and we are already working to expand and enhance the ability to manage GIST patients using this new agent alone or in combination therapies.
“The trial that we have performed shows that patients will benefit by control of GIST even in the absence of tumor shrinkage,” he added. “SU11248 can stabilize the disease and prevent worsening, which translates into disease control and longer survival for GIST patients whose disease is resistant to imatinib.”
About 60% of GISTs occur in the stomach, but they can appear anywhere along the length of the digestive system from the esophagus to the anus.
GISTS are rare. About 5,000 such tumors are diagnosed in the United States each year. GISTs usually affect middle-aged and older patients; they are more common among men, according to the American Cancer Society.
The exact causes of GIST are unknown, but research indicates that most GIST cells have an enzyme disorder relating to the tyrosine kinase enzyme. This enzyme is responsible for sending signals inside cells to stimulate growth and cell division. It may be associated with a family history but usually occurs spontaneously in the population.
For more information:
- Demetri G, van Oosterom A, Garrett C, et al. Sunitinib malate (SU11248) prolongs progression-free and overall survival for GIST patients after failure of imatinib mesylate therapy: Update of a phase III trial. Abstract #716. Presented at ECCO 13, the European Cancer Congress. Oct. 29-Nov. 3, 2005. Paris.