Bayer HealthCare and Onyx Pharmaceuticals recently announced that Bayer HealthCare has submitted a New Drug Application (NDA) to the FDA for the oral multikinase inhibitor regorafenib for the treatment of metastatic and/or unresectable gastrointestinal stromal tumors (GIST) in patients whose disease has progressed despite prior treatment.
Pivotal Phase III Trial
The submission is based on data from the pivotal phase III GRID trial, which showed that regorafenib plus best supportive care significantly improved progression-free survival compared to placebo plus best supportive care (HR = 0.27, 95% CI = 0.19-0.39; P < .0001) in patients with metastatic and/or unresectable GIST who were previously treated with imatinib (Gleevec) and sunitinib (Sutent). The median progression-free survival was 4.8 months in the regorafenib arm vs 0.9 months in the placebo arm and there was a positive trend in the regorafenib group in improving overall survival (HR = 0.77, 95% CI = 0.42-1.41; P = .20). In addition, the study design allowed patients receiving placebo to cross over following disease progression.
In this study, the most frequently reported drug-related adverse events (greater than or equal to 25%) in regorafenib-treated patients vs placebo-treated patients, respectively, were hand-foot skin reaction (56.1% vs 13.6%), hypertension (48.5% vs 16.7%), diarrhea (40.2% vs 4.5%), fatigue (38.6% vs 27.3%) and oral mucositis (37.9% vs 7.6%). Results from the study were presented at the ASCO Annual Meeting in June 2012.
In addition, the FDA recently agreed that Bayer can proceed with its expanded access program to provide regorafenib to patients diagnosed with GIST through qualified clinical sites participating in the expanded access program. For more information on this program, visit www.clinicaltrials.gov [NCT01646593].
GRID was a randomized, double-blind, placebo-controlled, multi-center, cross-over phase III study of regorafenib for the treatment of GIST. It randomly assigned 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 plus best supportive care or placebo plus best supportive care to evaluate efficacy and safety. Treatment cycles consisted of 160 mg regorafenib (or matching placebo) once daily for three weeks on/one week off plus best supportive care. The primary endpoint was progression-free survival, and secondary endpoints included overall survival, time to progression, disease control rate, tumor response rate, and duration of response. The safety and tolerability of the two treatment groups were also compared. ■