Bayer has submitted a supplemental new drug application to the FDA to have its cancer medication regorafenib (Stivarga) approved for the second-line treatment of patients with unresectable hepatocellular carcinoma (uHCC).
Regorafenib, an oral multi-kinase inhibitor, is currently indicated for patients with metastatic colorectal cancer who have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; with anti-vascular endothelial growth factor (VEGF) therapy; and, if RAS wild-type, with anti-epidermal growth factor receptor (EGFR) therapy, as well as for patients with locally advanced, unresectable, or metastatic gastrointestinal stromal tumors (GIST) who were previously treated with imatinib mesylate and sutinib maleate.
The FDA granted regorafenib a fast-track designation, which is an expedited program designed to facilitate the development and review of drugs that address unmet medical needs in the treatment of serious or life-threatening conditions.
The sNDA submission was based on positive data from the phase 3, placebo-controlled RESORCE (REgorafenib After SORafenib in Patients With HepatoCEllular Carcinoma) trial, which investigated regorafenib in 573 patients with uHCC whose disease had progressed during treatment with sorafenib (Nexavar, Bayer). The patients were randomly assigned to receive regorafenib or placebo plus best supportive care.
The patients received regorafenib (160 mg once daily) or placebo for three weeks on and one week off, with 28 days constituting one treatment cycle. The study’s primary endpoint was overall survival (OS). Secondary endpoints included the time to progression, progression-free survival (PFS), the objective tumor response rate, and the disease control rate.
The study met its primary endpoint of a statistically significant improvement in OS compared with placebo. Median OS was 10.6 months for regorafenib compared with 7.8 months for placebo.
After a median treatment period of 3.6 months, patients receiving regorafenib showed a 38% reduction in the risk of death and a 54% reduction in the risk of progression or death compared with placebo. Mean PFS was 3.1 months with regorafenib and 1.5 months with placebo. Overall, 65% of patients treated with regorafenib showed a complete or partial response or stable disease compared with 36% of the placebo group.
Severe drug-induced liver injury with fatal outcomes occurred in regorafenib-treated patients in placebo-controlled clinical studies. Regorafenib also caused increased rates of myocardial ischemia, infarction, hemorrhage, hand–foot skin reaction, severe rash, and hypertension.