CHICAGO―Imatinib is associated with prolonged progression-free survival (PFS) but not overall survival, compared to placebo, among patients with imatinib- or sunitinib-refractory advanced gastrointestinal stromal tumor (GIST), report authors of a randomized phase 3 clinical trial presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Rechallenge of imatinib significantly improves PFS and DCR [disease control rate] in patients with advanced GIST after failure of at least imatinib and sunitinib, likely by continuous kinase inhibition of the bulk of disease clones, which retain imatinib sensitivity,” reported Yoon-Koo Kang, MD, PhD, of the Asan Medical Center, University of Ulsan College of Medicine, in Seoul, South Korea, and coauthors.

“However, TKI [tyrosine kinase inhibitor]-resistant clones continue to progress, leading to relatively brief duration of benefit,” Dr. Kang cautioned.

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The coauthors enrolled 81 patients with metastatic or unresectable GIST, who had a prior benefit from first-line imatinib (defined as disease control for more than 6 months), progressive disease on imatinib or sunitinib, or intolerance to sunitinib. Patients were randomly assigned 1:1 to receive best supportive care and either oral imatinib 400 mg once daily (n=41) or placebo (n=40). At the time of disease progression, patients in the placebo group were allowed to cross over to open-label imatinib therapy.

PFS was determined by external radiology review, using RECIST v1.0 criteria.

Patients in the imatinib group had significantly prolonged PFS compared to those receiving placebo (1.8 vs. 0.9 months; P=0.002; hazard ratio [HR], 0.45; 95% CI: 0.27-0.76), Dr. Kang said.

“DCR at 12 weeks was 32% for imatinib versus 5% for placebo (P=0.003),” he reported.  But he also cautioned that “with 92.5% of placebo patients rapidly crossing over to imatinib, median overall survival was 8.2 months for imatinib versus 7.5 months for placebo (HR, 0.99; P=0.98).”

The most frequent grade 3 or higher AEs among imatinib patients during the double-blind treatment period were anemia (29%), fatigue (10%), and hyperbilirubinemia (7%), Dr. Kang noted.