Bayer HealthCare reported positive data from the Phase III GRID (GIST— Regorafenib in progressive disease) trial evaluating regorafenib in patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) whose disease had progressed despite prior treatment with imatinib and sunitinib. The GRID study met its primary endpoint of improvement in progression-free survival (PFS).
Bayer has submitted an NDA for the oral multikinase inhibitor for the treatment of patients with metastatic colorectal cancer. The company plans to submit an NDA for regorafenib in GIST in the second half of 2012.
GRID was a randomized, double-blind, placebo-controlled, multicenter, cross-over Phase III study. It enrolled 199 patients whose disease had progressed despite prior treatment with imatinib and sunitinib. Patients were randomized in a 2:1 ratio to receive either regorafenib (160 mg once daily, three weeks on/one week off) plus best supportive care (BSC) or placebo plus BSC. The primary endpoint of this trial was PFS, and secondary endpoints included overall survival, time to progression, disease control rate, tumor response rate, and duration of response.
The median PFS was 4.8 months in the regorafenib arm versus 0.9 months in the placebo arm. The most common drug-related, treatment-emergent adverse events (occurring in at least 10% of patients during double-blind treatment) included hand-foot skin reaction (56.1% vs.15.2%), hypertension (48.5% vs. 16.7%), diarrhea (40.9% vs.7.6%), fatigue (38.6% vs. 27.3%), oral mucositis (37.9% vs. 9.1%), alopecia (23.5% vs. 3.0%), hoarseness (22.0% vs. 4.5%), anorexia (20.5% vs. 7.6%), rash, maculopapular (18.2% vs. 3.0%), nausea (15.9% vs. 9.1%), constipation (15.2% vs. 7.6%), myalgia (13.6% vs. 9.1%), and voice alteration (11.4% vs. 3.0%) for patients receiving regorafenib as compared to placebo.