AstraZeneca's Gefitinib (Iressa) has had a bit of a chequered history since it's fast track approval by the the Japanese Health Authority in 2002 and the FDA in 2003 for non-small cell lung cancer (NSCLC). However, since the phase III trials did not appear to generate a significant overall survival advantage, it has been available in the US, Canada and Switzerland under strict labelling restrictions based on the ISEL study since 2005. A patient assistance program is available for suitable patients in the US:
"In the light of positive survival data with other agents including another oral EGFR inhibitor, physicians should use other treatment options in advanced non-small cell lung cancer patient populations who have received one or two prior chemotherapy and are refractory or intolerant to their most recent regimen."
Source: US Iressa PI
The IPASS study (IRESSA Pan-ASia Study) subsequently demonstrated superiority of gefitinib's efficacy over doublet chemotherapy in EGFR mutation positive patients in 2008. In Europe, this led to gefitinib being finally approved for the treatment of adults with locally advanced or metastatic NSCLC with activating mutations of EGFR-TK across all lines of therapy in 2009.
The latest data, from the North-East Japan Study Group, published in this weekend's NEJM, showed some interesting new results in a study of 239 newly diagnosed Asian patients with NSCLC and EGFR mutations when they compared standard chemotherapy of carboplatin plus paclitaxel to gefitinib as a single agent.
Essentially, in this front-line setting, treatment with the EGFR tyrosine kinase inhibitor gefitinib resulted in progression-free survival (PFS) that was twice as long as treatment with standard chemotherapy, ie PFS of 10.8 months in the gefitinib group compared with 5.4 months in the chemotherapy group. Response rates were also improved in the gefitinib arm compared to chemotherapy (73.7% vs. 30.7%). Side effects were as expected for the two treatments (rash and elevated aminotransferase in the gefinib group and neutropenia, anemia, loss of appetite and neuropathy in the chemotherapy group).
However, the median overall survival (OS) of 30.5 months vs 23.6 months was not significantly different between the two groups.
It is clear from both IPASS and the NE Japan studies that in a select sub-population of lung cancer patients, patients could elect to receive biologic therapy such as gefitinib rather than chemotherapy and have a reasonable quality of life.
However, given the lack of over survival benefit with Iressa but has been demonstrated with Tarceva (erlotinib) in other studies, I'm not sure where this leaves AstraZeneca. It is unlikely that the restrictions on the US or Canadian approvals will change as a result of this study.
Why Tarceva led to a survival benefit in EGFR mutated NSCLC and Iressa does not is still unclear at this stage.
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T, & North-East Japan Study Group (2010). Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. The New England journal of medicine, 362 (25), 2380-8 PMID: 20573926