IRESSA (gefitinib) was the first in a new class of anti-cancer drugs, known as epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors, to gain market approval (first approval was in Japan in 2002) and is currently licensed for the treatment of advanced non-small-cell lung cancer (NSCLC) in 36 countries worldwide. Approvals were based on two phase II trials, IDEAL 1 and 2, which showed IRESSA to be an effective treatment for many patients with previously-treated advanced NSCLC. Approximately 50% of patients in the IDEAL trials achieved tumour shrinkage or stabilisation of their tumour and the drug was found to be generally well tolerated with the most commonly reported adverse drug reactions being mild-to-moderate skin rash and diarrhoea [1, 2].

In 2004 the results of the phase III ISEL (IRESSA Survival Evaluation in Lung Cancer) study were reported. This study compared IRESSA with placebo in patients with refractory advanced NSCLC who were ineligible for further chemotherapy [3]. ISEL showed some improvement in survival with IRESSA but this failed to reach statistical significance, compared with placebo, in the overall population or in patients with adenocarcinoma. Pre-planned subgroup analyses showed a statistically significant increase in survival with IRESSA, compared with placebo, in patients of Asian origin and in patients who had never smoked.

Following the announcement of the ISEL data, regulatory authorities in the USA and Canada limited the use of IRESSA to those patients already experiencing benefit from the drug. Licences for IRESSA were not restricted in Japan and Asia Pacific where the drug has become an established therapy for pre-treated advanced NSCLC.

In July 2007 AstraZeneca announced that the phase III INTEREST (IRESSA Non-small cell lung cancer Trial Evaluating REsponse and Survival against Taxotere) study met its primary objective and demonstrated non-inferiority in overall survival for IRESSA relative to docetaxel in patients with advanced NSCLC who were eligible for further chemotherapy after treatment with a platinum-based regimen. Based on these data, AstraZeneca has filed a European Marketing Authorisation Application (MAA) for IRESSA in pre-treated advanced NSCLC. Results of a pan-Asian phase III study of IRESSA as first-line therapy for advanced NSCLC are expected in 2008.


References

1. Fukuoka M et al. J Clin Oncol 2003; 21: 2237-2246.
2. Kris M et al. J Am Med Assoc 2003; 290: 2149-2158.
3. Thatcher N et al. Lancet 2005; 366: 1527-1537.