Bayer files applications in US., Japan and Europe for Stivarga (regorafenib) to treat unresectable hepatocellular carcinoma.

Bayer announced the submission of applications to extend the marketing authorization for its oral multi-kinase inhibitor regorafenib in the U.S., Japan and Europe, for the second line treatment of patients with unresectable hepatocellular carcinoma (HCC) (liver cancer). Regorafenib is already approved under the brand name Stivarga in many countries to treat metastatic colorectal cancer and metastatic gastrointestinal stromal tumors.

The regulatory submissions for regorafenib are based on data from the international, multicenter, placebo-controlled Phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma] trial. The trial investigated regorafenib in patients with unresectable hepatocellular carcinoma (HCC) whose disease had progressed during treatment with sorafenib (Nexavar) tablets. Results showed that regorafenib significantly improved overall survival (OS) compared to placebo (HR 0.63; 95% CI 0.50-0.79; p<0.001), which over the trial period represents a 37 percent reduction in the risk of death for patients who received regorafenib plus best supportive care (BSC) compared to patients treated with placebo plus BSC. The median OS was 10.6 months in patients treated with regorafenib, compared to 7.8 months in patients who received placebo plus BSC. The safety and tolerability was generally consistent with the known profile of regorafenib, with no clinically meaningful differences in health-related quality of life (HRQoL) between the regorafenib and placebo plus BSC groups. In the U.S., regorafenib has received Fast Track designation, which is an expedited program designed to facilitate the development, and expedite the review of drugs to address an unmet medical need in the treatment of a serious or life-threatening condition.

Comment: Cyramza (ramucirumab) from Eli Lilly is in Phase III for second line hepatocellular carcinoma.The REACH-2 trial is due to complete in April 2018. Cometriq (cabozantinib) from Exelixis is in development and both Keytruda from Merck Inc.and Opdivo from BMS have early stage trials in hepatocellular carcinoma.