For GI stromal tumor, three years of imatinib better than one

Last Updated: 2015-11-04

By Larry Hand

NEW YORK (Reuters Health) - The current standard three years of adjuvant imatinib leads to longer survival than one year of treatment for patients with high-risk gastrointestinal stromal tumor (GIST), according to a new study.

Longer observation of these patients is still needed, however, researchers say.

"Patients who complete three years of adjutant imatinib need to be followed up longitudinally, and have CT or MRI of the abdomen and the pelvis done periodically," Dr. Heikki Joensuu of the Comprehensive Cancer Center Helsinki and the University of Helsinki, Finland, told Reuters Health by email.

"Should GIST come back, it will usually respond well to restarting imatinib, but it is likely important to restart imatinib early when the tumor bulk is still small. Two ongoing trials are comparing longer than three-year duration of adjuvant imatinib to the current standard," he said.

Dr. Joensuu and colleagues analyzed data on 400 patients who had macroscopically completely excised KIT-positive GIST with a high risk of recurrence per National Institutes of Health criteria. They randomly assigned patients after surgery to receive imatinib 400 mg oral daily for one or three years.

During a median follow-up of 90 months, five-year recurrence-free survival, the primary endpoint, was 71.1% for the three-year patients compared with 52.3% for the one-year patients (hazard ratio, 0.60; p<0.001).

Survival, the secondary endpoint, was 91.9% for the three-year patients compared to 85.3% for the one-year patients (HR, 0.60; p=0.036).

Overall, there were 171 recurrences and 69 deaths during the open-label trial, the team reports in the Journal of Clinical Oncology, online November 2.

In a subset of patients with centrally confirmed GIST and without macroscopic metastases at study entry, patients in the three-year group also had longer survival than one-year patients(93.4% versus 86.8%; HR, 0.53; p=0.024).

Almost 27% of patients in the three-year group and almost 13% of patients in the one-year group discontinued treatment early due to adverse events but not due to GIST recurrence.

"The most frequent side effects are eyelid edema, muscle cramps, and diarrhea, and mild anemia is also frequent," Dr. Joensuu said. "Most patients tolerate adjuvant imatinib administered for three years well, but not everyone."

"The mutational status of the tumor influences sensitivity to imatinib," Dr. Joensuu explained. "Patients whose GIST harbors a mutation in the part of the KIT gene called exon 11 benefit most from adjuvant imatinib. A few GISTs are resistant to imatinib. Similarly GISTS that lack mutation in either the KIT gene or the PDGFRA gene usually do not benefit from adjuvant imatinib. In general, patients whose GIST has a high cell proliferation rate benefit more than patients whose GIST grows slowly."

Dr. Christopher C. Corless of the Oregon Health and Science University in Portland, who has studied imatinib but was not involved in the new work, told Reuters Health by email, "The message is the same for both the one-year and three-year adjuvant studies: patients at high risk of recurrence of their GIST (large tumor size, high mitotic index) clearly benefit from imatinib."

"Careful pathological assessment of a resected primary GIST is critical to determining the likelihood of tumor recurrence. In particular, the mitotic index (mitoses per 5mm squared) must be assessed accurately, as mitotic index is the single best predictor of disease recurrence," Dr. Corless said.

"Molecular subtyping of GISTs is also very important if adjuvant imatinib is under consideration. Many experts do not treat patients who have a KIT/PDGFRA-wildtype tumor. And some experts treat patients with an exon 9-mutant GIST using a higher daily dose (800 mg)," he added.

In summary, he concluded, "Among the different molecular subtypes of GISTs, the Joensuu study showed a trend favoring maximal benefit of adjuvant treatment in the exon 11-mutant group. This is consistent with the observations from our study."

SOURCE: http://bit.ly/1Rt4pEL

J Clin Oncol 2015.