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FDA Approves Regorafenib for Advanced Colorectal Cancer

Ben Leach
Published: Thursday, Sep 27, 2012

Regorafenib (Stivarga) packagingThe FDA has approved regorafenib (Stivarga), an oral multikinase inhibitor, to treat patients with metastatic colorectal cancer (mCRC) whose disease has progressed after prior therapy after a pivotal clinical trial showed that the drug improved both progression-free survival (PFS) and overall survival (OS) in these patients.

The drug was approved based on the results of the phase III CORRECT trial, which were presented at the 2012 meeting of the American Society of Clinical Oncology (ASCO).

“Stivarga is the latest colorectal cancer treatment to demonstrate an ability to extend patients’ lives and is the second drug approved for patients with colorectal cancer in the past two months,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, in a statement. The FDA also recently approved ziv-aflibercept (Zaltrap) for metastatic colorectal cancer when given in combination with the FOLFIRI (leucovorin calcium, fluorouracil, irinotecan hydrochloride) chemotherapy regimen.

Regorafenib obstructs multiple tumor pathways, inhibiting targets and receptors including VEGFR1-3, TIE2, PDGFR, FGFR, KIT and RET. These pathways are implicated in processes such as angiogenesis and tumor progression.

In the CORRECT trial, 760 patients with mCRC were randomized 2:1 to receive regorafenib (160 mg orally once daily on a 3-weeks-on/1-weekoff cycle; n = 505) or placebo (n = 255), plus best supportive care. In order to be eligible for the study, the patients’ diseases had to have progressed within 3 months of receiving standard treatments, including chemotherapy, bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix).

An interim analysis showed that patients who received regorafenib had a median OS of 6.4 months compared with 5.0 months in patients who received a placebo (hazard ratio [HR] = 0.77; 95% CI, 0.64—0.94; P = .0052). A statistically significant improvement was also seen in PFS, with patients in the regorafenib arm experiencing a median PFS of 1.9 months compared with 1.7 months in the placebo arm (HR = 0.49; 95% CI, 0.42—0.58; P < .000001). The benefits were observed across all prespecified subgroups, including patients who had either wild type or mutated KRAS. The results were favorable enough that the study was unblinded and patients in the placebo arm were allowed to crossover into the regorafenib arm.

The most common grade 3/4 adverse events in the regorafenib arm were hand-foot skin reaction (16.6%), fatigue (9.6%), hypertension (7.2%), diarrhea, (7.2%), and rash (5.8%). There were five patients in the regorafenib arm with grade 5 adverse events, compared with zero patients in the placebo arm.

In another study that was presented at ASCO 2012, the phase III GRID trial showed that regorafenib was able to delay disease progression in patients with gastrointestinal stromal tumors (GISTs). Last month, it was announced that a FDA new drug application had been submitted for regorafenib to treat patients with metastatic or unresectable GIST whose disease had progressed after prior treatment.

Stivarga is marketed by Wayne, NJ-based Bayer HealthCare Pharmaceuticals.


Van Cutsem E, Sobrero AF, Siena S, et al. Phase III CORRECT trial of regorafenib in metastatic colorectal cancer (mCRC). J Clin Oncol. 2012;30(suppl; abstr 3502).



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