A Recent Study Supports Targeted therapy to Reduce the Risk of Recurrence in GIST
Earlier this year, the FDA approved imatinib (Gleevec®) for the treatment of GIST (Gastrointestinal Stromal Tumor) following surgery, based on a study reporting that longer treatment can lead to longer survival among patients at high risk of recurrence.* The 2011 study compared patients who took the drug for one year to those who took it for three years. Patients who took the drug longer were more likely to be alive five years later. It might seem obvious that longer treatment would lead to better survival rates, but earlier studies have not found that to be true. While the drug helps stop recurrence of GIST, it hasn’t been shown to improve long term survival in these patients. This new study is thus important because it seems to contradict earlier findings. However, the study hasn’t been fully analyzed yet. It will be particularly important to confirm these results and to see if tumor markers can predict which patients are most likely to benefit from imatinib. Please read the expanded summary below by an N-of-One expert for further details and analysis of the study's impact.
In work discussed for the first time at the American Society of Clinical Oncology meeting in Chicago in June, 2011, Heikki Joensuu described the results of the combined Scandinavian Sarcoma Group (SSG) / German Sarcoma Group (AIO) study XVII. In a previous study of no treatment after surgery versus 1 year of imatinib, fewer people had their GIST (gastrointestinal stromal tumor) come back if they took imatinib for a year (in comparison to not at all), but there was no difference in survival regardless of whether someone received no extra therapy or 1 year of imatinib.
In the SSG/AIO study, people with GIST believed to be at high risk of recurrence after surgical removal of the original tumor received either 1 or 3 years of imatinib, and then were followed by scans for tumor recurrence. Deaths from the cancer were also recorded. People in whom their GIST came back were allowed to start imatinib and could continue treatment of any kind for as long as they wanted. As expected, there were fewer people who had their tumor come back early if they took 3 years of imatinib, instead of 1 year. However, the surprising finding was that people who took 3 years of imatinib had better overall survival than those who took only 1 year of imatinib. 92% of people with higher risk GISTs were alive at 5 years compared to 82% of those who took only one year of imatinib after surgery.
Researchers were somewhat surprised by this study as it was felt that even 3 years of imatinib was not necessarily expected to prolong survival, based on the older study as well as older data. There are also caveats to this study. We do not know the molecular profile of people who went on the study with respect to issues such as their KIT mutation status, and the like, which could have affected the outcomes. These data are pending. Nonetheless, they support the use of 3 years of imatinib for people who have higher risk of GIST recurrence. The determinants of what defines high risk are in the eye of the doctor and person being treated.
The so-called “Rule of Fives” may help determine who should receive adjuvant imatinib and who should not. This “rule” states that gastric GISTs that are both >5 cm in greatest size (about 2 inches), as well as dividing actively (what is termed as 5 dividing cells (mitoses) per 50 high powered fields), define higher risk GIST patients for whom adjuvant imatinib may be most reasonable. Part two of the rule indicates that for non-gastric GIST, either the large size or high “mitotic rate” is enough to consider the tumor a high risk GIST for therapy.
Many of these data and “rules” that guide treatment may change as we learn more about the imatinib study and also more about the mutation status of the participants. A patient’s molecular profile is likely to be a factor that may determine the potential usefulness of imatinib in this so called “adjuvant” setting for GIST patients.
References:
1. Dr. Robert Maki, Medical Director, Sarcoma Program, and Chief of Pediatric Hematology / Oncology at the Mount Sinai Medical Center, New York, NY
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