Nexavar® for Kidney Cancer

In December 2005, the FDA approved Nexavar® (sorafenib) tablets for the treatment of patients with advanced renal cell carcinoma (RCC), or kidney cancer.

Nexavar was approved in the United States following data presented at the 2005 Annual Meeting of the American Society of Clinical Oncology (ASCO) from an ongoing Phase 3 clinical trial that demonstrated Nexavar was well-tolerated and significantly delayed disease progression in patients with advanced kidney cancer. As assessed by independent radiologic review, progression-free survival (PFS) doubled to a median value of 24 weeks (167 days) in patients receiving Nexavar, compared to 12 weeks (84 days) for patients receiving placebo. (HR=0.72; p=< 0.000001).

In July 2006, the European Commission granted marketing authorization for the use of Nexavar in the treatment of patients with advanced kidney cancer who have failed prior interferon-alpha or interleukin-2 based therapy or who are considered unsuitable for such therapy.

Nexavar is currently approved in more than 90 countries worldwide for the treatment of patients with advanced kidney cancer.

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