Erlotinib

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.

Tarceva (Roche)
25 mg, 100 mg and 150 mg tablets
Approved indication: non-small cell lung cancer
Australian Medicines Handbook section 14.3.9

In some cancers there is over expression of epidermal growth factor receptors. These receptors are linked to tyrosine kinase and increased tyrosine kinase activity is associated with angiogenesis and tumour progression. This enzyme is therefore a target for drug therapy (see 'Angiogenesis inhibitors in cancer' Aust Prescr 2006;29:9-12 and Angiogenesis inhibitors in cancer' Aust Prescr 2006;29:13-15).

Erlotinib inhibits the tyrosine kinase associated with epidermal growth factor receptors. It is uncertain what effect it has on other tyrosine kinase enzymes.

As epidermal growth factor receptors are present in some lung cancer cells, erlotinib has been studied in patients whose cancers have progressed despite chemotherapy. In one trial seven of 57 patients who took erlotinib daily had a complete or partial response.¹ Erlotinib was then used in a double-blind placebo-controlled study of 731 patients with stage IIIB or IV non-small cell lung cancer which had previously been treated with chemotherapy. Less than 1% of the placebo group responded compared with 8.9% of the erlotinib group. Although erlotinib improved survival, the patients only lived for a median of 6.7 months while those in the placebo group survived for 4.7 months.²

During the double-blind trial 76% of the patients given erlotinib developed a rash. This required some people to reduce their dose. Other adverse effects with a frequency greater than placebo included stomatitis, infection, diarrhoea, anorexia and ocular toxicity.2

The bioavailability of erlotinib is greatly increased by food so the tablets should be taken at least one hour before or two hours after meals. Erlotinib is metabolised mainly by cytochrome P450 3A4 so there is a potential for interactions with drugs that inhibit or induce this enzyme. Caution is needed if the patient is taking warfarin. The half-life of erlotinib is 36 hours, but its clearance may be increased in smokers. No pharmacokinetic data are available on the use of erlotinib in patients with liver metastases.

The role of erlotinib still requires clarification. There is a possibility that patients who develop a rash survive longer¹ and there is debate about the efficacy of erlotinib in patients whose tumours do not over express epidermal growth factor receptors. There is no benefit in giving erlotinib with chemotherapy so its use is restricted to patients whose locally advanced or metastatic non-small cell lung cancer progresses after chemotherapy. Whether erlotinib has an overall advantage over gefitinib, another tyrosine kinase inhibitor with the same indication, is currently uncertain.

manufacturer provided all requested information

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).