The US Food and Drug Administration (FDA) approved Bayer's Stivarga (regorafenib) tablets for the second-line treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with Nexavar (sorafenib).

Stivarga is the first and only treatment to demonstrate significant improvement in overall survival in second-line HCC patients. In the RESORCE trial, Stivarga was shown to provide a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo; the median OS was 10.6 [(n=379) (CI 9.1, 12.1)] vs 7.8 [(n=194) (CI 6.3, 8.8)] months, respectively (HR 0.63, 95% CI 0.50-0.79; p<0.0001). This translates to a 37% reduction in the risk of death. The number of deaths in each arm included 233 of 379 (62%) with Stivarga and 140 of 194 (72%) with placebo. FDA has approval to expands Bayer’s leadership in liver cancer with a treatment plan in HCC involving use of Stivarga directly after progression on Nexavar.

Stivarga is an oral inhibitor of multiple kinases involved in normal cellular functioning and in pathological processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity. The FDA’s approval is based on data from the international, multicenter, placebo-controlled phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma; NCT 01774344] trial, which investigated patients with HCC whose disease had progressed during treatment with Nexavar. The most frequently observed adverse drug reactions (=30%) in patients treated with regorafenib vs. placebo-treated patients in HCC, respectively, were: pain (55% vs. 44%), HFSR/PPE (51% vs. 7%), asthenia/fatigue (4FDA Stivargahepatocellular carcinoma HCCBayerNexavar oral inhibitor  oncogenesis, tumor angiogenesis, metastasis and tumor immunity. The FDA’s approval is based on data from the international, multicenter, placebo-controlled phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma; NCT 01774344] trial, which investigated patients 2% vs. 33%), diarrhea (41% vs. 15%), hypertension (31% vs. 6%), infection (31% vs. 18%), decreased appetite and food intake (31% vs. 15%).

“Hepatocellular carcinoma is very hard to treat, and with no new treatments in nearly a decade, options have been very limited for physicians and patients,” said Dr Jordi Bruix, lead investigator for the RESORCE trial, BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBEREHD, Spain. “The US. approval of Stivarga for hepatocellular carcinoma therefore provides a significant step forward in addressing the high unmet need in this patient population.”

The incidence of liver cancer is increasing worldwide and it is already the sixth most common cancer in the world and the second leading cause of cancer-related deaths globally.

“Bayer is proud to have played a significant role in the treatment of hepatocellular carcinoma,” said Robert LaCaze, executive vice president and head of the Oncology Strategic Business Unit at Bayer. “We first embarked on our scientific research in this area 20 years ago. We could not have done it alone: we would like to thank the patients, caregivers and investigators for their participation and engagement in the RESORCE trial.”

The approval of Stivarga in liver cancer marks the third time that this therapy has been granted FDA approval on a priority basis. The FDA granted Fast Track designation to Stivarga in HCC, which is an expedited program designed to facilitate development and review of drugs to address an unmet medical need in the treatment of a serious or life-threatening condition. The FDA also granted Orphan Drug Designation (ODD) to Stivarga in HCC. The ODD program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and disorders. Additional regulatory filings for Stivarga in HCC are under review in countries around the world, including the EU, Japan and China. Decisions in the EU and Japan regions are expected later this year.