FDA Approves Gleevec to Prevent Recurrence of Rare Gastrointestinal Cancer

By Jerry Call
LRG Science Coordinator

The following press release was reprinted from the Food & Drug Administration website.

The U.S. Food and Drug Administration today approved Gleevec (imatinib mesylate) for a new indication – keeping cancer from growing in patients following surgical removal of a gastrointestinal stromal tumor or GIST.

GIST is a fairly rare form of cancer that originates in cells found in the wall of the GI tract. These cells, known as interstitial cells of Cajal, are part of the autonomic nervous system, which helps to control the movement of food and liquid through the stomach and intestines. Gleevec, first approved by the FDA in 2001, is one of the first drugs in a class of agents that block cellular communications that result in tumor growth

“Approval of Gleevec offers health care professionals and patients an important new therapeutic option for patients with this uncommon gastrointestinal disease,” said Richard Pazdur, M.D., director, Office of Oncology Drug Products, Center for Drug Evaluation and Research, FDA. “It illustrates how the continued study of a once novel drug throughout its product lifecycle can yield new and important uses.”

About 5,000 to 6,000 new patients are diagnosed with GIST each year in the United States. Because symptoms of GIST are no different than other GI complaints such as nausea and vomiting, the cancer is difficult to detect early. Patients initially undergo surgery to remove the tumor but GIST commonly recurs. Gleevec is intended to be given to patients following surgery to help prevent tumor recurrence.

The efficacy of Gleevec was established in a clinical trial in which patients received either Gleevec or a placebo for one year after surgical removal of the tumor. The optimal treatment duration is not known.

There were significantly fewer recurrences of GIST in patients receiving Gleevec than in patients who did not. The most frequently reported adverse reactions were diarrhea, fatigue, nausea, swelling of the feet, decreased red blood cell counts, rash, vomiting and abdominal pain.

Gleevec is manufactured by Novartis AG, Basel, Switzerland.

LRG Notes

Although there are still some questions about adjuvant Gleevec for GIST, the new FDA approval has few restrictions. The approval is for “Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST”. As noted in the FDA press release, “the optimal treatment duration is not known” and no treatment duration is specified in the revised Gleevec prescribing information. In the Z9001 trial, patients that received Gleevec took it for one year and then stopped the Gleevec. Other trials are underway that examine longer treatment periods. The other limitation in the Z9001 trial was that the resected primary tumor had to be at least three cm in size, but there is no such limitation in the approval.

There are still some questions about which patients might benefit the most from adjuvant treatment. It’s easy to speculate that patients with a high risk of recurrence and Gleevec-responsive mutational types will be more likely to benefit than patients with low-risk tumors or less Gleevec-responsive types of mutations. Ronald DeMatteo, MD, of Memorial Sloan-Kettering Cancer Center in New York was the principal investigator of the pivotal Z9001 trial that led to adjuvant Gleevec approval for GIST in the United States.

According to Dr. DeMatteo, “We may learn more [about those types of questions] in the next year or so as we do subtype analyses.”