Gleevec Interruption in GIST Associated with Resistance, Recurrence, Death

Stopping Gleevec treatment for advanced gastrointestinal stromal tumors (GIST) can lead to faster resistance and increase the risk of the disease getting worse or leading to death.

Interruption of treatment with Gleevec (imatinib) among some patients with advanced gastrointestinal stromal tumors (GIST) has been found by researchers to be associated with a faster occurrence of resistance to Gleevec and an increased risk of disease progression or death.

In the phase 3 BFR14 study, findings of which were published in The Lancet Oncology, patients with advanced GIST were divided into two groups: those with stable or responding disease whose treatment was discontinued then restarted at the time of progression in the interruption group or those who received continuation of treatment until progression in the continuation group. Interruption of treatment, researchers noted, was associated with rapid disease progression among patients in the interruption group after one year, three years and five years.

At a median follow-up of 235.2 months after the one-year randomization, 200.9 months after the three-year randomization and 164.5 months after the five-year randomization, the median progression-free survival (the time a patient lives without their disease spreading or worsening) in the interruption and continuation groups was 6.1 months versus 27.8 months after one year of Gleevec, seven months versus 67 months after three years of Gleevec and 12 months versus not reached (meaning fewer than half of the patients in that arm experienced disease progression or died) after five years of Gleevec.

Likewise, the median time until resistance to Gleevec was 28.7 months in the interruption group and 90.6 months in the continuation group after one year on Gleevec, 66.2 months versus 127.3 months after three years and 58.6 months versus not reached after five years, researchers reported.

Additionally, the median overall survival (the time a patient lives, regardless of disease status) was 56 months in the interruption group and 105 months in the continuation group after one year on Gleevec, 104 months versus 134 months after three years and not reached versus 110.4 months after five years, according to the study findings.

At 12 years, 9% of patients in the interruption group were still alive versus 50% of the continuation group after the three-year randomization, compared to 33% and 83% of patients, respectively, after the five-year randomization.

“[Gleevec] interruption in patients with GIST without progressive disease is not recommended,” researchers wrote in the introduction to their findings. “[Gleevec] interruption in non-progressing patients with GIST was associated with rapid progression, faster resistance to [Gleevec] and shorter overall survival in the long-term follow-up when compared with [Gleevec] continuation in patients after three years and five years of [Gleevec].”

These observa­tions have possible relevance for chronic myeloid leukemia and other cancers treated with tyrosine kinase inhibitors, a class of drugs that includes Gleevec, researchers noted.

GIST, according to the American Cancer Society, is a group of uncommon cancers that begin in the cells in the wall of the gastrointestinal, or digestive, tract. Approximately 60% of cases of GIST begin in the stomach, and about 35% of cases begin in the small intestine, with most of the rest found in the esophagus, colon and rectum, with a small amount developing in the abdomen, the American Cancer Society explained, noting that approximately 4,000 to 6,000 cases of GIST are diagnosed in the United States each year. GIST, the organization stated, is most commonly diagnosed among people older than 50, but can develop among people of any age.

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