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.

Tykerb (GlaxoSmithKline)
250 mg tablets
Approved indication: breast cancer
Australian Medicines Handbook section 14.3.9

Lapatinib is a new drug for use in combination chemotherapy with capecitabine for patients with metastatic breast cancer. It is indicated for patients with tumours over expressing HER2 (human epidermal growth factor receptor type 2) that have progressed after treatment with an anthracycline, a taxane and trastuzumab. Lapatinib causes growth arrest or cell death of tumour cells by reversibly inhibiting the intracellular tyrosine kinase domain of HER1 (human epidermal growth factor receptor type 1) and HER2.

Following oral administration of lapatinib, peak plasma concentrations are reached after approximately four hours. It is extensively metabolised, primarily by CYP3A4 and CYP3A5, then eliminated in the faeces.

Concomitant use of drugs that inhibit or induce CYP3A4, such as ketoconazole or carbamazepine, affect lapatinib's pharmacokinetics so dose adjustment of lapatinib with these drugs may be needed. The systemic exposure of lapatinib is increased in patients with moderate to severe hepatic impairment. As the bioavailability of lapatinib is increased with food, it should be taken at least one hour before or after eating.

Preliminary studies have indicated that lapatinib has biological and clinical activity against various solid tumours (including breast, ovarian and lung) that over express HER1 and HER2.1,2 An interim analysis of the efficacy and safety of lapatinib in combination with capecitabine has been further evaluated in an open label phase III trial. In the study, 324 women with progressive HER2 positive locally advanced or metastatic breast cancer who had already tried other treatments (including anthracycline, a taxane and trastuzumab) were randomised (in a 1:1 ratio) to receive either a lapatinib plus capecitabine combination or capecitabine alone. Lapatinib was given as a 1250 mg continuous daily dose and capecitabine was given as 2000 mg (when in combination) or 2500 mg (as monotherapy) per square metre of body surface in two divided doses for 14 days of a 21-day cycle.3

Clinical data were collected for 20 months after the enrolment of the first patient. During this period, data from 274 of the 324 enrolled women were collected for evaluation.

Overall survival rates were similar in both groups, with 36 deaths in the lapatinib plus capecitabine group and 35 in the capecitabine group. The overall response rate was 22% in the combination group and 14% in the monotherapy group. Patients on combination therapy had a longer median time to disease progression or death compared to those taking capecitabine alone (8.4 months vs 4.4 months).3

Diarrhoea was more common in women taking lapatinib plus capecitabine compared to those taking capecitabine alone (60% vs 39%). Dyspepsia and rash were also more common in the combination treatment group. Hand-foot syndrome, nausea and vomiting occurred to a similar degree in both groups. There were five fatal adverse events in the study; two women on combination treatment and three women on monotherapy. The death of a patient with diarrhoea, vomiting and small-bowel obstruction in the monotherapy group was deemed to be related to the study drug.3

Lapatinib has been associated with decreases in left ventricular ejection fraction, and asymptomatic cardiac events were detected in 2% of patients taking combination therapy in the trial.3 Therefore patients should be evaluated before starting therapy and at 8–12 week intervals during treatment to ensure that cardiac function does not decline.

Although lapatinib in combination with capecitabine prolongs the time to disease progression in women with metastatic breast cancer, it does not actually improve overall survival rates compared to capecitabine on its own.

manufacturer provided only the product 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 (

At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (