A prospective, randomized, multicenter, Phase III trial showed that three years of treatment with imatinib (Gleevec) after surgery in patients with high-risk gastrointestinal stromal tumors (GIST) improved overall and recurrence-free survival compared to one year of treatment. The findings could result in the three-year course of therapy becoming the new standard of care for those patients who are at risk for relapse.

"Earlier studies have shown an improvement in recurrence-free survival with one year of adjuvant imatinib treatment, but we were surprised to also see better numbers with overall survival after three years of therapy," said lead author Heikki Joensuu, M.D., professor of oncology at Helsinki University Central Hospital in Helsinki, Finland. "This might be the first example of long-term adjuvant therapy with a targeted small molecule tyrosine kinase inhibitor, and it's likely to become standard treatment."

GIST tumors, which usually begin in the stomach or intestine, are a type of soft-tissue sarcoma. Imatinib targets the abnormal proteins encoded by mutated KIT and PDGFR-alpha genes, which are found in approximately 90 percent of GIST. One year of imatinib is now considered the standard adjuvant treatment for operable GIST. Approximately 85 percent of patients who have advanced GIST respond to imatinib, with partial remission or stable disease lasting a median of two years.

In the study 400 patients with GIST who were at high risk for recurrence were randomized to either one or three years of imatinib after surgery. After a median follow up time of 54 months, the investigators found that five-year recurrence-free survival was higher in the three-year group (65.6 percent) compared to patients treated for one year (47.9 percent). Similarly, the five-year overall survival for the three-year group was higher - 92.0 percent - compared to 81.7 percent of patients who received adjuvant imatinib for only one year.

Imatinib was generally well tolerated and the majority of side effects were typical of patients receiving the drug: anemia, fatigue, nausea, diarrhea and muscle cramps. However, 7.7 percent of the patients in the one-year group and 13.7 percent of the patients who received three years of adjuvant therapy halted treatment because of adverse events.

Few patients developed resistance to adjuvant imatinib, which is in line with previous studies. Only 2 percent (4) and 6.1 percent (12) of patients in the 12- and 36-month groups, respectively, stopped treatment due to GIST recurrence while receiving imatinib.

Dr. Joensuu stressed the need for continued monitoring of the trial participants, in addition to new research aimed at better identifying patients who could benefit from long-term adjuvant imatinib. Studies analyzing GIST risk factors and addressing longer treatment times with adjuvant imatinib - including a single-arm, non-randomized study examining 5-year adjuvant treatment - are currently underway.

The study was funded by Novartis, and also received academic funding.