Long-term impact of imatinib on metastatic gastrointestinal stromal tumours (GIST)

The EORTC 62005 study, recently published in Journal of Clinical Oncology demonstrated that patients with metastatic GIST continue to benefit from imatinib, a targeted therapy, with 13% of patients reported to be alive 10 years from starting treatment. It also confirmed that genomics might help predict whether a patient with metastatic GIST could benefit from a stronger dose of imatinibfor overall survival.

In this study, 916 patients were enrolled in 10 countries in Europe. Half were randomized to receive 400 mg of imatinib daily, while the other half received the same dose twice daily. Patients included in the study had advanced or metastatic GIST as characterized by c-KIT expression and a WHO performance status of less than 4.

After 10 years, there was still no significant difference between the two arms in Progression-Free Survival (9.5% in 400mg daily and 9.2% in 800 mg daily) or Overall Survival (19.4% and 21.5% respectively). However, the increased follow-up now makes it possible to show that patients with a KIT mutation of 9 or more had a significantly better survival with a higher dose.

“While it has been common knowledge that chemotherapy is largely inactive in GIST, , at the time we initiated this trial, there was little hope for GIST patients,” said Paolo Casali, one ot the Principal Investigator for the study. “Imatinib has since changed the treatment landscape for these patients, and this trial not only shows good 10-year survival results in that patient population, but it has also provided an opportunity to learn about new patterns for tumour response and the occurrence of secondary resistance.”

Because imatinib has become first-line treatment for metastatic and non-metastatic GIST patients, today there is little visibility on outcomes for these patients, a gap EORTC is trying to address in part with the ALTGIST study in collaboration with ATITG (link to 1321 study). However, this study provides data to help identify subsets of patients most likely to have a better prognostic overall, and also whether some with a subset of metastatic GIST are most likely to benefit from a highly active molecularly targeted agent such as imatinib.