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Longest Ever Follow-Up Study OF A Targeted Cancer Therapy Shows Excellent Results

After five years on Gleevec, overall survival of people with chronic myelogenous leukemia reaches 89 percent, and they become less likely to experience disease progression over time

The overall survival of most people with chronic myelogenous leukemia (CML) treated with imatinib (Gleevec, STI-571) is extremely high and the relapse rate is quite low, according to new data from a study out of the Oregon Health & Science University Cancer Institute. The overall survival at five years is 89 percent as compared to no more than 50 percent with prior therapies, and the risk of relapse continues to decrease the longer patients take the drug.    

 "This represents a complete turn around in the prognosis for patients with this disease," said Brian J. Druker, M.D., who originally collaborated with Novartis scientists to develop Gleevec into a successful treatment for CML. He is the JELD-WEN chair of leukemia research in the OHSU Cancer Institute and an investigator of the Howard Hughes Medical Institute.   

Druker presented the five-year update from the IRIS (International Randomized IFN vs. ST1571) Study Group on Saturday, June 3 at the 2006 annual meeting of the American Society of Clinical Oncology in Atlanta, Ga.  

Begun in June 2000, the phase III trial involved 1,106 subjects at 117 centers in 16 countries. Subjects were in CML's chronic phase, the most common stage of the disease, and had not previously received chemotherapy. Half were randomized to receive Gleevec and half to receive the standard treatment at the time the trial started, interferon-alpha and cytarabine arabinoside. Participants in the interferon arm were later allowed to cross over to Gleevec. Just 3 percent remain on interferon therapy.   

 "Prior to this, we had to project what the five-year survival data would be and worried that the risk of relapse might increase. With this data, we have increased confidence in this targeted therapy," Druker said.   

At five years, the overall survival of the 553 subjects randomized to receive Gleevec as their initial therapy was 89 percent; 95 percent if only deaths related to CML are considered. Just 5 percent of subjects discontinued Gleevec because of side effects. Severe side effects included skin rashes, elevated liver enzymes and fluid retention. More common and less severe side effects included puffiness around the eyes, mild nausea, diarrhea and muscle cramps.   

The risk of relapse has trended down during the past three years. In the study's fourth year, fewer than 1 percent of patients progressed from the chronic phase to the accelerated phase or to blast crisis. "This trend, if it holds, coupled with the low risk of relapse, means that the possibility of long-term survival with CML is increasingly likely," Druker said.   

Druker's scientific and clinical research of the molecular cause of CML was instrumental in the development of Gleevec, a signal transduction inhibitor that interferes with the enzymes that trigger the spread of cancerous cells. It acts on CML by inhibiting an enzyme produced by the BCR-ABL gene that tells cells to grow and divide.   

Clinical trials with Gleevec began a new era in cancer treatment in which cancerous cells are targeted based on their molecular abnormality and healthy cells are left unharmed.   

"What we hope to do in the future is to apply the Gleevec principle more broadly," said Druker, who serves on the Human Cancer Genome Anatomy Project steering committee. "We need a Gleevec for every cancer."   

In 2001, the U.S. Food and Drug Administration (FDA) broke a record for cancer therapy approval by fast-tracking Gleevec, approving it in less than three months for CML patients who failed interferon. It was approved for a rare and difficult to treat abdominal cancer, gastrointestinal stromal tumors (GIST), in 2002. In the following year, it also earned the FDA's approval for use in children, the first new pediatric cancer drug treatment in more than a decade. Gleevec is being studied as a potential therapy for certain types of blood and skin cancers.

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