Stivarga was granted a priority review by the FDA to treat certain patients with liver cancer in the second line setting.
Stivarga (regorafenib) was granted a priority review to a supplemental new drug application (sNDA) by the FDA to be used in the second-line setting for patients with unresectable hepatocellular carcinoma (HCC), according to Bayer, the manufacturer of the drug.
The sNDA is based on the phase 3 RESORCE trial, in which the median overall survival (OS) was 10.6 months with Stivarga plus best supportive care compared with 7.8 months for placebo plus best supportive care, representing a 38 percent reduction in the risk of death.
"Liver cancer is one of the few cancers still on the rise, and though Nexavar has been approved for the treatment of patients with unresectable HCC since 2007, effective second-line systemic treatment options are urgently needed," Dario Mirski, M.D., senior vice president and head of medical affairs for the Americas at Bayer, said in a statement. "The priority review for Stivarga paves the way for us to gain regulatory approval as early as possible for the HCC patients who need it most."
The phase 3 RESORCE study randomized 573 patients with HCC in a 2 to 1ratio to receive best supportive care plus either Stivarga (379 patients) or placebo (194 patients). Stivarga was administered at 160 mg once daily for three weeks followed by one week without treatment.
The median age of patients was 63 years, with the majority being male (88 percent). Most patients had tumors that were BCLC stage C (87 percent). Prior Nexavar (sorafenib) was administered for 20 or more days at 400 mg/day or more with documented radiologic progression. The primary endpoint of the study was OS, with secondary outcome measures focused on progression-free survival (PFS), objective response rate (ORR) and safety.
Median PFS was 3.1 months in the Stivarga arm compared with 1.5 months in the placebo group, representing a 54 percent reduction in the risk of progression or death. The median time to progression in the Stivarga group was 3.2 versus 1.5 months with placebo.
The ORR with Stivarga was 10.6 percent versus 4.1 percent with placebo. When considering stable disease, the overall disease control rate was 65.2 percent with the multikinase inhibitor versus 36.1 percent with placebo.
Median duration of treatment was 3.6 months with Stivarga (range, 0.03-29.4) versus 1.9 months with placebo (range, 0.2-27.4). Grade 3 or higher adverse events (AEs) were experienced by 79.7 percent of those treated with Stivarga versus 58.5 percent of patients in the placebo arm. Dose modifications to alleviate AEs were required for 68.2 percent of patients in the experimental arm compared with 31.1 percent of patients treated with placebo.
The most common grade 3 or higher AEs with Stivarga versus placebo, respectively, were hypertension (15.2 percent vs 4.7 percent), hand-foot skin reaction (12.6 percent vs 0.5 percent), fatigue (9.1 percent vs 4.7 percent) and diarrhea (3.2 percent vs 0 percent). There were more deaths in the placebo arm versus Stivarga within 30 days following the last dose of treatment (13.4 percent with Stivarga vs 19.7 percent for placebo).
Stivarga is an oral kinase inhibitor that blocks VEGFR 1-3, TIE-2, RAF-1, BRAF, BRAFV600, KIT, RET, PDGFR and FGFR. The agent is currently FDA approved for the treatment of patients with metastatic colorectal cancer and advanced gastrointestinal stromal tumors.