The US Food and Drug Administration (FDA) has approved AstraZeneca's Iressa (gefitinib) tablets, 250mg once daily, for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test.

Iressa is an oral, EGFR tyrosine kinase inhibitor (TKI), which works by blocking the activity of the EGFR tyrosine kinase enzyme responsible for regulating signalling pathways implicated in the growth and survival of cancer cells. Iressa was granted Orphan Drug designation by the FDA in August 2014 for the treatment of EGFR mutation-positive NSCLC.

Antoine Yver, head of oncology, global medicines development at AstraZeneca said “The approval of Iressa provides physicians and patients in the US with a new choice of first-line treatment for metastatic non-small cell lung cancer. AstraZeneca is at the forefront of research into targeted therapies for EGFR mutated lung cancer and is committed to improving the outlook for patients at all stages of the disease.”

AstraZeneca has partnered with Qiagen to provide the therascreen EGFR companion diagnostic test for Iressa in the US. The test rapidly identifies EGFR mutation status through a tumour tissue sample, in order to guide the use of Iressa in the treatment of patients with metastatic NSCLC.

The FDA approval of Iressa is based on data from the phase IV IFUM1 (Iressa Follow-Up Measure) study, assessing Iressa as a first-line treatment for Caucasian patients with locally advanced or metastatic EGFR mutation-positive NSCLC. This was supported by results from the IPASS2 (Iressa Pan-ASia Study) clinical trial. A total of 106 EGFR mutation-positive patients were enrolled to the study. The overall response rate (ORR) by investigators’ assessment was 70 per cent (95 per cent confidence interval (CI) 61 per cent to 78 per cent). ORR by a Blinded Independent Centre Review (BICR) was 50 per cent (95 per cent CI 41 per cent to 59 per cent).

The most common adverse events (AEs) in the IFUM study were rash (44.9 per cent), diarrhoea (30.8 per cent), vomiting (13.1 per cent ), asthenia, cough and dry skin (all 11.2 per cent), and nausea (10.3 per cent). Two patients (1.9 per cent) experienced a serious AE that the investigator characterised as related to treatment, and 4 patients (3.7 per cent) experienced drug related AEs that led to treatment discontinuation.

Iressa is a targeted monotherapy for the treatment of patients with advanced or metastatic epidermal growth factor receptor mutation-positive non-small cell lung cancer (NSCLC). Iressa acts by inhibiting the tyrosine kinase enzyme in the EGFR, thus blocking the transmission of signals involved in the growth and spread of tumours. EGFR mutations occur in approximately 10 to 15 per cent of NSCLC Caucasian patients and 30 to 40 per cent of NSCLC patients in Asia.

Iressa is approved in 91 countries for the treatment of adult patients with locally advanced or metastatic EGFR mutation-positive NSCLC. The safety profile of Iressa is well established through a large, global clinical programme and extensive real world evidence. The most commonly reported adverse events for Iressa are diarrhoea and skin reactions including rash, acne, dry skin and pruritus.

AstraZeneca is also studying Iressa in combination with other investigational medicines, including the company’s anti-PD-L1 monoclonal antibody, durvalumab (MEDI4736) to assess its potential as a combination treatment for a broader range of lung cancer patients.