IMPORTANT SAFETY INFORMATION

Nexavar in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. 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. An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider permanent discontinuation of Nexavar. continue reading below »

Study design and objectives in the Asia-Pacific Study

A multicenter, phase 3, randomized, double-blind, placebo-controlled trial conducted in China, Taiwan, and South Korea¹

* The functional status of a cancer patient, as assessed by the Eastern Cooperative Oncology Group (ECOG) score.

End points¹:

Overall survival (OS), time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety
No predefined primary end point

Key inclusion criteria¹:

Patients from 23 centers in China, South Korea, and Taiwan were considered eligible if they had:
- Histologically or cytologically proven HCC
- Advanced HCC
- ≥1 measurable untreated lesion according to RECIST
- ECOG PS 0-2
  - Child-Pugh class A (mild hepatic impairment)
  - No prior systemic treatment

Treatment continuation¹:

Treatment with Nexavar or placebo was continued until adverse reactions requiring discontinuation of study treatment, progression of disease, pregnancy, deterioration or ECOG PS to 4, development of an additional form of cancer, withdrawal of consent, or death.

Comparison of baseline patient characteristics between Sharp trial and AP study

RECIST=Response Evaluation Criteria In Solid Tumors;
ECOG PS=Eastern Cooperative Oncology Group performance status.

Adverse reactions highlights for the AP Study¹

The most common adverse reactions reported for Nexavar vs placebo in this study, respectively, were: hand-foot skin reaction (HFSR) (45% vs 2.7%), diarrhea (25.5% vs 5.3%), alopecia (24.8% vs 1.3%), fatigue (20.1% vs 8.0%), rash/desquamation (20.1% vs 6.7%), and hypertension (18.8% vs 1.3%). These events were primarily Grade 1/2
The most common adverse reactions resulting in dose reductions were HFSR (11.4%) and diarrhea (7.4%)

Indication

Nexavar (sorafenib) is indicated for the treatment of patients with unresectable hepatocellular carcinoma.

Important Safety Considerations

Nexavar in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer
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
An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider permanent 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, if 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. Nexavar should be discontinued if Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected as these may be life-threatening
Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar. Discontinue Nexavar in the event of a gastrointestinal perforation
Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time (PT), International Normalized Ratio (INR) or clinical bleeding episodes
Temporary interruption of Nexavar therapy is recommended in patients undergoing major surgical procedures
Nexavar in combination with gemcitabine/cisplatin is not recommended in patients with squamous cell lung cancer. The safety and effectiveness of Nexavar has not been established in patients with non-small cell lung cancer
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
Drug-induced hepatitis with Nexavar may result in hepatic failure and death. Liver function tests should be monitored regularly and in cases of increased transaminases without alternative explanation Nexavar should be discontinued
Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while on Nexavar and female patients should also be advised against breastfeeding while receiving Nexavar
Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar
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 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%

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. Cheng AL, Yang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomized, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25-34. 2. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4)378-390.

IMPORTANT SAFETY INFORMATION

Study design and objectives in the Asia-Pacific Study

End points1:

Key inclusion criteria1:

Treatment continuation1:

Adverse reactions highlights for the AP Study1