The FDA has approved Bayer's Stivarga (regorafenib) tablets to treat patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Stivarga was previously approved by the FDA in September 2012 for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.

Stivarga is a Bayer compound developed by Bayer and jointly promoted by Bayer and Onyx Pharmaceuticals in the U.S. In 2011, Bayer entered into an agreement with Onyx, under which Onyx receives a royalty on all global net sales of Stivarga in oncology.

The approval of Stivarga in GIST is based on data from the pivotal phase III GRID (GIST - Regorafenib In Progressive Disease) trial, which showed that Stivarga plus best supportive care (BSC) statistically significantly improved progression-free survival (PFS) compared to placebo plus BSC (HR=0.27 [95% CI 0.19-0.39], p<0.0001) in patients with locally advanced, unresectable or metastatic GIST who have been previously treated with imatinib mesylate and sunitinib malate. The median PFS was 4.8 months in the Stivarga arm versus 0.9 months in the placebo arm (p<0.0001). There was no statistically significant difference in overall survival at the time of the planned interim analysis based on 29% of the total events for the final analysis. At the time of disease progression as assessed by central review, the study blind was broken and all patients were offered the opportunity to take Stivarga at the investigator's discretion.

Fifty-six (85%) patients randomized to placebo and 41 (31%) patients randomized to Stivarga received open-label Stivarga.

The most frequently observed adverse events (≥30%) in Stivarga-treated patients versus placebo-treated patients in GIST, respectively, were: hand-foot skin reaction (HFSR)/palmar-plantar erythrodysesthesia (PPE), hypertension, asthenia/fatigue, diarrhea, mucositis, dysphonia, infection, decreased appetite and food intake and rash. The Stivarga label includes a boxed warning citing the risk of hepatotoxicity. Severe and sometimes fatal hepatotoxicity has been observed in clinical trials.

"While great progress has been made in the treatment of GIST since the introduction of kinase inhibitors as effective therapies for this orphan disease, we have been looking for additional, effective treatments for GIST patients whose disease worsens despite currently approved therapies," said George D. Demetri, MD, PI of the GRID study and director of the center for sarcoma and bone oncology at the Dana-Farber Cancer Institute in Boston. "These data show that regorafenib can slow disease progression in patients who are no longer responding to other approved therapies and may provide another avenue for GIST patients who would otherwise have no FDA-approved treatment option."