The 2010 Gastrointestinal American Society of Clinical Oncology conference was held January 22-24, 2010 in Orlando, Florida. Several of the abstracts/ posters are summarized below.
Risk assessment for tumor recurrence after surgical resection of localized primary gastrointestinal stromal tumor (GIST): North American Intergroup phase III trial ACOSOG Z9001
Abstract # 6
ME. Blackstein et al
Dr. Blackstein (University of Toronto) and colleagues reported on maturing data from the Z9001 adjuvant Gleevec trial. In this trial, 713 patients took either Gleevec or placebo for 12 months. With a median follow-up of 20 months, the recurrence-free survival (RFS) was 91 percent for the imatinib arm and 74 percent for the placebo arm.
NOTE: This study was unblinded in April 2007. Some patients in the imatinib arm may have continued imatinib after one year (they received imatinib outside of the clinical trial) and some placebo patients were switched over to receive the drug or may have taken the drug after the trial was stopped. Both situations would make interpreting the data more difficult. In spite of this, recurrence is clearly reduced or delayed for patients taking imatinib in the moderate and high risk categories (See Table 1).
Final results from a phase III study of IPI-504 (retaspimycin hydrochloride) versus placebo in patients with gastrointestinal stromal tumors following failure of kinase inhibitor therapies
Abstract # 64
G.D. Demetri et al
This randomized phase III trial was terminated early due to the occurrence of four ontreatment related deaths in the IPI-504 arm. These deaths were considered drug-related and included kidney failure, liver failure, metabolic acidosis and cardiopulmonary arrest. Grade three or four AST or ALT abnormalities (indicates injury/damage to liver cells) were present in three of the four deaths. The authors concluded “…In this heavily pretreated patient population, IPI-504 was not well tolerated at this dose and schedule, and the study was terminated early.” IPI-504 continues to be evaluated at lower doses and alternative schedules in other clinical trials for patients with other forms of cancer.
In an accompanying poster, a relationship between prior liver surgery and safety was noted. Of the six patients on IPI-504 with prior liver surgery, there were three on-study deaths not due to GIST (50%). Of 26 patients on IPI-504 with no prior liver surgery, there was only one on-study death not due to GIST (3.8%). The poster also noted that the patient population in this trial had advanced disease, as evidenced by deaths during the screening period and short progression-free survival in the placebo arm (33 days).
A cross-sectional study of imatinib plasma trough levels in patients with advanced gastrointestinal stromal tumors: Impact of gastrointestinal resection on exposure to imatinib.
Abstract # 161
C. Yoo et al
Dr. Yoo and colleagues from the University of Ulsan College of Medicine and the Asian Medical Center, Seoul, South Korea; report that in a series of 108 GIST patients, higher imatinib levels (Cmin) were correlated with advanced age (p=0.02), low creatinine clearance (p=0.001), low hemoglobin (p=0.01), and albumin concentrations (p<0.001). Imatinib concentrations (Cmin) were also significantly lower in 17 patients with a total or subtotal gastrectomy (937±339 ng/mL) compared to the 75 patients without a gastrectomy (1388±656 ng/mL). The authors concluded in part that “…monitoring imatinib plasma levels may be important for patients with low Cmin levels, especially those who have undergone major gastrectomy.”
NOTE: While the optimal concentration of imatinib has not been firmly established, preliminary data found a longer time to progression for patients with plasma levels above 1,100 ng/mL (Demetri et al.). We would also note that while patients with a gastrectomy in this series were found to have lower plasma levels, other series have reported no difference between patients with versus without a gastrectomy.
High frequency of synchronous adenocarcinomas in patients with gastrointestinal stromal tumors
Abstract # 23
B. Garicochea et al
This retrospective study looked at one hundred Brazilian GIST patients treated at two centers. Fourteen percent of these patients were found to have another type of cancer during the treatment planning stage. According to the authors, this rate is much higher than observed in the majority of human cancers. The accompanying GIST was frequently discovered incidentally.