The orally administered investigational multikinase inhibitor regorafenib demonstrated “notable anticancer activity” in a phase II trial among patients with advanced gastrointestinal stromal tumor (GIST) who developed resistance to imatinib (Gleevec) and sunitinib (Sutent). Researchers reported in the Journal of Clinical Oncology that clinical benefit, defined as complete or partial response or stable disease ≥ 16 weeks, was documented in 26 (75%) of the 33 eligible patients. Four patients had stable disease ≤ 16 weeks, two had disease progression at first tumor evaluation, and one withdrew from the study before the first tumor assessment.
The median progression-free survival was 10 months and overall survival had not been reached at the time the study was published. Six patients had died, five secondary to disease progression and one from an unrelated illness. An international phase III trial evaluating regorafenib in this setting is underway
“Patients received regorafenib orally, 160 mg daily, on days 1 to 21 of a 28-day cycle,” the researchers noted. Hand-foot skin reaction occurred in 85% of patients, fatigue in 79%, hypertension in 67%, and diarrhea in 61%. Most of these events were grade 1, but grade 3 or 4 hypertension occurred in 34% of patients, hand-foot skin reaction in 24%, and hypophosphatemia in 15%.
“Despite the majority of patients requiring at least one dose reduction for toxicity, many patients were able to have the regorafenib dose re-escalated without recurrence of unacceptable adverse effects,” the investigators stated. “Only one patient discontinued participation in the study because of toxicity,” the authors added, “suggesting that in this cohort, toxicity was manageable with dose modification and other supportive measures.” ■
George S, et al: J Clin Oncol 30:2401-2407, 2012.