This article is more than 5 years old. Information may no longer be current.
Long-term imatinib treatment may improve OS, RFS in high-risk GISTs
Click Here to Manage Email Alerts
An extended course of adjuvant imatinib increased survival among patients with high-risk gastrointestinal stromal tumors, according to study results.
This suggests that high rates of 5-year survival are achievable among patients with gastrointestinal stromal tumors (GISTs) — one of the most common single types of soft tissue sarcoma — according to the researchers.
“Patients who have undergone surgery for high-risk GISTs have a substantial risk for recurrence, often exceeding 50% within the next 5 years following surgery,” Heikki Joensuu, MD, PhD, professor of oncology at University of Helsinki, told HemOnc Today. “My colleagues and I speculated that patients with high-risk GIST might be the ones who benefit the most from adjuvant imatinib, and that the duration of treatment might also matter.”
A 3-year course of adjuvant imatinib (Gleevec, Novartis) is recommended for patients with high-risk GISTs, based on survival findings from the Scandinavian Sarcoma Group XVII/AIO trial.
Joensuu and colleagues performed a second planned analysis of the trial to determine whether survival benefits persisted.
The open-label study included 400 patients with macroscopically completely excised, KIT-positive GIST with a high recurrence risk. Following surgery, the researchers assigned patients to adjuvant imatinib for 1 year (n = 199) or 3 years (n = 198)
RFS served as the primary endpoint. OS served as a secondary endpoint.
Median follow-up was 89 months in the 1-year group and 90 months in the 3-year group. During this time, the researchers observed 171 recurrences and 69 deaths.
Significantly more patients assigned the 3-year course of imatinib achieved 5-year RFS than those assigned to 1 year of therapy (71.1% vs. 52.3%; HR = 0.6; 95% CI, 0.44-0.81).
Further, more patients who received the longer imatinib course achieved 5-year OS (91.9% vs. 85.3%; HR = 0.6; 95% CI, 0.37-0.97).
Among patients in the 3-year arm, a subset of patients with centrally confirmed GIST and without macroscopic metastases at study entry survived longer (5-year OS, 93.4% vs. 86.8%; HR = 0.53; 95% CI, 0.3-0.93).
All but two patients reported an adverse event; however, the majority of adverse events were mild. Fifty-three patients (26.8%) in the 3-year group and 25 patients (12.6%) in the 1-year group discontinued therapy early for nonrecurrence reasons.
A similar number of cardiac adverse events and instances of second cancers occurred in both groups.
The researchers acknowledged limitations of their study. They assigned all patients to the standard imatinib dose (400 mg per day), despite evidence that a higher dose may have produced more favorable outcomes in patients with a KIT exon 9 mutation.
Further, the study enrolled patients with the PDGFRA D842V mutations; the researchers report that it is now evident that these patients are unlikely to benefit from imatinib.
In an interview, Joensuu told HemOnc Today that the Scandinavian Sarcoma Group plans to study whether further extended courses of imatinib continue to confer a significant benefit.
“We have opened a trial for accrual where 5 years of adjuvant imatinib will be compared to the current standard duration of 3 years,” Joensuu said. “Another randomized trial, also being conducted in Europe, is comparing 6 years of imatinib to 3 years.” – by Cameron Kelsall
For more information:
Heikki Joensuu, MD, PhD, can be reached at Comprehensive Cancer Center Helsinki and University of Helsinki, Haartmaninkatu 4, POB 180, FIN-00029 Helsinki, Finland; email: heikki.joensuu@hus.fl.
Disclosure: Joensuu reports consultant roles with ARIAD Pharmaceuticals, Blueprint Medicines and Orion Pharma. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts