Drug Detail

Information about Stivarga

Generic Name	Regorafenib
IND	BAY 73-4506
Brand Name (US)	Stivarga
Manufacturer	Bayer
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Approved for GIST (3rd line)
Indications	GIST, Colon Cancer
Overall Strategy	KIT Protein Based
Strategy	Block KIT + Block blood vessel growth
Drug Category	KIT/PDGFRA inhibitor

Sept, 27, 2012 - Regorafenib (Stivarga) was approved for advanced colorectal cancer. It was approved for GIST in the United States and Japan in 2013 and in the European Union in 2014.

April 3, 2012 Bayer issued a press release stating that the phase III trial for regorafenib in advanced GIST (GRID trial) had met its primary endpoint of a statistically significant progression-free survival (PFS). See Trial Result links below.
In this trial, the median PFS time for placebo was 0.9 months. The median PFS time for regorafenib was 4.8 months. This result was highly statistically significant. Because patients were allowed to crossover from placebo to regorafenib, overall survival was not a primary endpoint. The primary endpoint of the trial was PFS. No new treatment related side effects were noted. An exploratory analysis showed benefit for multiple subtypes, including exon 9 and exon 11 patients. In data presented at 2013 ASCO, several patients with SDH-deficient GIST were reported to have responded to regorafenib with some shrinkage.

Regorafenib is a potent oral multi-kinase inhibitor with a kinase inhibition profile targeting angiogenic and oncogenic receptor tyrosine kinases (TK). In a phase II trial for kidney cancer, 50% of patients had stable disease and 31% had a partial response for a benefit rate of 81%. In a randomized phase III clinical trial, regorafenib significantly improved overall survival for advanced colorectal cancer (CRC) patients.

Preliminary reports from early GIST trials suggested significant activity in 3rd line GIST patients (see Trial Results links below). This led to a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo for subjects with metastatic and/or unresectable GIST whose disease had progressed despite prior treatment with at least imatinib and sunitinib. This trial opened in January, 2011 and completed recruitment by the summer of 2011. See the phase III trial link below for more information about this trial (in the "Trials of this drug" section).

Side effects:
In the GIST phase III trial, Grade 3 (more severe) side effects included hypertension (22.7%), hand-foot syndrome (19.7%), diarrhea (5.3%), fatigue (2.3%), mucositis (1.5%) and hair loss (1.5%). Nausea, constipation and myalgia were also noted.
In a phase II trial for kidney cancer, the most common drug-related adverse events (all grades) were hand-foot skin reaction (HFSR), fatigue, hypertension, mucositis, diarrhea, alopecia, rash, voice changes, anorexia, nausea, constipation and vomiting.

Dose: The recommended dose is 160 mg/day for 3 weeks followed by one week off drug.