Nexavar is the first approved oral targeted therapy for liver cancer and the only one shown to significantly improve overall survival in patients with the disease.

Nexavar® for Liver Cancer

In 2007, the FDA approved Nexavar® (sorafenib) tablets in a second indication, unresectable hepatocellular carcinoma (HCC), or liver cancer, in the United States. In the EU, Nexavar was approved in HCC. The approvals were based on positive data from the international, Phase 3, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial, which demonstrated that Nexavar extended overall survival in patients with HCC versus those taking placebo by 44% (HR=0.69; p=0.0006).

Data presented at the American Society of Clinical Oncology (ASCO) annual meeting in June 2007 showed that median overall survival for Nexavar-treated patients was 10.7 months compared to 7.9 months in those taking placebo.

Bayer and Onyx halted the SHARP trial in February 2007 when an independent data monitoring committee (DMC) concluded during a planned interim analysis that the trial met its primary endpoint, resulting in superior overall survival (OS) in those patients receiving Nexavar versus those patients receiving placebo. There were no significant differences in serious adverse event rates between the Nexavar- and placebo-treated groups, with the most commonly observed serious adverse events in patients receiving Nexavar were diarrhea and hand-foot-skin reaction. As a result of the DMC anlysis, the trial was stopped and all patients enrolled in the trial were given access to Nexavar.

Nexavar is currently approved in more than 80 countries for the treatment of patients with liver cancer.

Bayer and Onyx have multiple clinical trials underway for individuals with liver cancer.

Important Safety Considerations

Hypertension may occur early in the course of treatment. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter and treat, as required.

An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider discontinuation of Nexavar.

Cardiac ischemia and/or myocardial infarction may occur. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischemia and/or myocardial infarction.

Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar.

Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in unresectable HCC, respectively, were: diarrhea (55% vs 25%), fatigue (46% vs 45%), abdominal pain (31% vs 26%), weight loss (30% vs 10%), anorexia (29% vs 18%), nausea (24% vs 20%), and hand-foot skin reaction (21% vs 3%). Grade 3/4 adverse reactions were 45% vs 32%.

Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in advanced RCC, respectively, were: diarrhea (43% vs 13%), rash/desquamation (40% vs 16%), fatigue (37% vs 28%), hand-foot skin reaction (30% vs 7%), alopecia (27% vs 3%),and nausea (23% vs 19%). Grade 3/4 adverse reactions were 38% vs 28%.

Hand-foot skin reaction and rash are common and management may include topical therapies for symptomatic relief. In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of Nexavar should be considered. Temporary interruption of Nexavar therapy is recommended in patients undergoing major surgical procedures.

Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Caution is recommended when administering Nexavar with compounds that are metabolized/eliminated predominantly by the UGT1A9 pathway, UGT1A1 pathway (eg, irinotecan), doxorubicin, docetaxel, fluorouracil, and substrates of CYP2B6 and CYP2C8, and CYP3A4 inducers. Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes.

Women of childbearing potential are advised to avoid becoming pregnant and against breastfeeding.