IMPORTANT SAFETY INFORMATION

NEXAVAR in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and female patients should also be advised against breastfeeding while receiving Nexavar. Cardiac ischemia and/or myocardial infarction may occur. continue reading below »

TARGET* efficacy

Overall survival (OS) results

Final median OS (uncensored)¹
- 17.8 months with Nexavar (n=451) vs 15.2 months with placebo (n=452)
  HR: 0.88; 95% CI, 0.74-1.04 (P=.146)
- Did not meet criteria for statistical significance
Final OS results confounded due to crossover¹
- 48% (n=216) of placebo patients crossed over to Nexavar therapy

Important Safety Consideration

Uncommon but serious adverse reactions, including keratoacanthomas/squamous cell cancer of the skin and Stevens-Johnson Syndrome, have been reported in clinical trials
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Nexavar—Doubled progression-free survival (PFS)²

Progression-free survival (PFS) in second-line patients

HR=hazard ratio; CI=confidence interval.
^αIndependently assessed data.

Safety considerations

Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Monitor patients taking concomitant warfarin regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Avoid concomitant use of strong CYP3A4 inducers, when possible, because inducers can decrease the systemic exposure of sorafenib. Nexavar exposure decreases when co-administered with oral neomycin. Effects of other antibiotics on Nexavar pharmacokinetics have not been studied
Women of childbearing potential are advised to avoid becoming pregnant and against breastfeeding
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PFS was consistent across all subsets analyzed^2†

MSKCC=Memorial Sloan-Kettering Cancer Center.
^† The study was not powered to assess differential patient response to treatment by subsets and no adjustments were made for multiple comparisons. The subset analyses were based on data collected before placebo patients were allowed to cross over to Nexavar therapy, were made to be descriptive only, and cannot be used to conclude whether a real difference in treatment effect exists between subsets.

A series of patient subsets were examined in exploratory univariate analyses of PFS
PFS benefit demonstrated regardless of²:

Age
Presence of lung or liver metastases
Risk category
Prior cytokine therapy
Time since diagnosis

Reported adverse reactions

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
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The majority of patients achieved stable disease²

The gain in PFS for Nexavar-treated patients primarily reflects the stable disease population
Tumor response was determined by independent radiological review by RECIST criteria

Of 672 patients evaluable for response²:
- PR with Nexavar: 2% (7/335) vs 0% (0/337) with placebo
- SD with Nexavar: 78% (261/335) vs 55% (186/337) with placebo
- PD with Nexavar: 9% (29/335) vs 30% (102/337) with placebo

CR=complete response; PR=partial response; SD=stable disease.
Independent review according to RECIST.
RECIST=Response Evaluation Criteria In Solid Tumors.
*TARGET (Treatment Approaches in Renal Cancer Global Evaluation Trial): A randomized, double-blind, placebo-controlled, multicenter, phase 3 study in patients with advanced RCC who had received 1 prior systemic therapy (N=903).¹ Read more about:

Indication

Nexavar is indicated for the treatment of patients with advanced renal cell carcinoma.

Important Safety Considerations

Nexavar in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer
Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and female patients should also be advised against breastfeeding while receiving 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
Uncommon but serious adverse reactions, including keratoacanthomas/squamous cell cancer of the skin and Stevens-Johnson Syndrome, have been reported in clinical trials
An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider discontinuation of Nexavar
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
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
Nexavar can prolong the QT/QTc interval and increase the risk for ventricular arrhythmias. Avoid use in patients with congenital long QT syndrome and monitor patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities
Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Monitor patients taking concomitant warfarin regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Avoid concomitant use of strong CYP3A4 inducers, when possible, because inducers can decrease the systemic exposure of sorafenib. Nexavar exposure decreases when co-administered with oral neomycin. Effects of other antibiotics on Nexavar pharmacokinetics have not been studied
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%
During postapproval use of Nexavar, the following adverse drug reactions have been identified: angioedema and drug-induced hepatitis, including reports of hepatic failure and death

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1.800.FDA.1088. For important risk and use information, please see the full Prescribing Information.

References: 1. Escudier B, Eisen T, Stadler WM, et al; TARGET Study Group. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009;27(20):3312-3318. 2. Escudier B, Eisen T, Stadler WM, et al; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125-134.