Phase 3 results have shown that regorafenib (Stivarga, Bayer) tablets achieved a median overall survival improvement in patients with unresectable hepatocellular carcinoma (HCC) who progressed after treatment with sorafenib (Nexavar, Bayer). The study found that patients treated with regorafenib had a median overall survival (OS) of 10.6 months compared with 7.8 months for patients given placebo plus best supportive care (BSC) (hazard ratio [HR], 0.62; P < 0.001).
The RESORCE (REgorafenib After SORafenib in Patients With HepatoCEllular Carcinoma) trial was a randomized, double blind, placebo-controlled, multicenter study of regorafenib in patients with HCC whose disease had progressed after treatment with sorafenib. The trial enrolled approximately 573 patients, who were randomly assigned to receive either regorafenib plus BSC or placebo plus BSC.
The patients were treated with regorafenib 160 mg once daily for three weeks on/one week off or placebo, with 28 days constituting one full treatment cycle. The study’s primary endpoint was OS, and secondary efficacy endpoints included the time to progression, progression-free survival (PFS), the objective tumor response rate, and the disease control rate. Safety and tolerability were continuously monitored.
In addition to the primary endpoint, all secondary endpoints were met. Median PFS was 3.1 months in patients treated with regorafenib compared with 1.5 months in the control group (HR, 0.46; P < 0.001). The median time to progression was 3.2 months versus 1.5 months, respectively (HR, 0.44; P < 0.001). The disease control rate (composed of complete or partial responses and stable disease) was 65.2% versus 36.1%, respectively (P < 0.001). Overall response rates (complete and partial response) were 10.6% versus 4.1% (P = 0.005), respectively.
The treatment-emergent adverse events (grade 3 or greater) occurring more frequently in the regorafenib group than in the placebo group included hypertension (15.2% vs. 4.7%, respectively), hand–foot skin reaction (12.6% vs. 0.5%), fatigue (9.1% vs. 4.7%), and diarrhea (3.2% vs. 0%).
Bayer plans to submit data from the RESORCE study as the basis for marketing authorization of regorafenib in the treatment of patients with unresectable HCC in the United States in 2016.
In the U.S., regorafenib is currently indicated for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy, and, if RAS wild type, an anti-epidermal growth factor receptor (EGFR) therapy. It is also indicated for the treatment of patients with locally advanced, unresectable, or metastatic gastrointestinal stromal tumors (GISTs) who have previously been treated with imatinib mesylate and sunitinib malate.
Source: Bayer; June 28, 2016.