Stivarga Gains FDA Approval for Liver Cancer

The Food and Drug Administration (FDA) has approved Stivarga (regorafenib) as a second-line treatment for patients with unresectable hepatocellular carcinoma (HCC) who have previously received Nexavar (sorafenib).

The approval 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 (HR, 0.62; 95 percent CI, 0.50-0.78; P <.001).

Limited treatment options are available for patients with liver cancer,” Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence, said in a statement. “This is the first time patients with HCC have had an FDA-approved treatment that can be used if their cancer has stopped responding to initial treatment with sorafenib.”

The phase 3 RESORCE study randomized 573 patients with HCC in a 2:1 ratio to receive best supportive care plus either Stivarga (n = 379) or placebo (n = 194). 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 was administered for ≥20 days at ≥400 mg/day 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 (HR, 0.46; 95 percent CI, 0.37-0.56; P <.001). The median time to progression in the Stivarga group was 3.2 versus 1.5 months with placebo (HR, 0.44; 95 percent CI, 0.036-0.55; P <.001).

The ORR with Stivarga was 10.6 percent versus 4.1 percent with placebo (P = .005). 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 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 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.