Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
200 mg tablets
Approved indication: renal cell cancer
Australian Medicines Handbook section 14.3.9
Sorafenib (BAY 43-9006) is a tyrosine kinase inhibitor. Its action on multiple receptors reduces tumour proliferation and angiogenesis. In animal studies it reduced the growth of renal cell carcinoma in mice.
A phase II trial of sorafenib included 202 patients with metastatic refractory renal cell cancer. All the patients took 400 mg sorafenib twice daily for 12 weeks. After 12 weeks 73 patients whose tumours had shrunk by at least 25% continued treatment. A group of 65 patients whose tumours had not shrunk by 25% were randomised to continue sorafenib or a placebo. (Patients whose tumours had progressed were withdrawn from the study.) Twelve weeks after randomisation 16 of the 32 patients taking sorafenib were progression free, compared with 6 of the 33 patients taking placebo.1
A phase III trial randomised 769 patients with advanced renal cell cancer that had progressed despite a previous systemic therapy, such as interferon. The median time from randomisation to disease progression was 167 days for patients taking sorafenib and 84 days for those taking a placebo.
Patients should probably take sorafenib on an empty stomach as food can reduce bioavailability. Sorafenib is metabolised in the liver by glucuronidation and cytochrome P450 3A4, but no dose adjustment is recommended for patients with mild-moderate liver impairment. Sorafenib has not been studied in patients with severe renal impairment, but only 20% of a dose is excreted in the urine.
Adverse events are common. In the phase II trial many of the patients developed rashes or a hand-foot skin reaction. Most were able to continue treatment. Nausea, diarrhoea and fatigue were also common. Approximately 17% of the patients in the phase III study developed hypertension while taking sorafenib, so regular monitoring of blood pressure is needed. Myocardial ischaemia was more frequent with sorafenib than with placebo (2.9% vs 0.4%). Consider discontinuing treatment if myocardial ischaemia develops. Bleeding occurred in 15% of the patients taken sorafenib and in 8% of the placebo group. Particular caution is needed if the patient is taking sorafenib and warfarin. Common laboratory abnormalities include lymphopenia, neutropenia, hypophosphataemia and elevated lipase.
Although sorafenib can reduce tumour size, only 2% of the patients in the phase III trial had an objective response. The drug therefore seems to keep the disease stable. At the time of writing the effect on survival was uncertain. An interim analysis reported that the median survival was 19.3 months with sorafenib and 15.9 months with placebo.
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Notes on references
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
- Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:2505-12.