Mature results from a landmark Phase-III trial have confirmed that patients with EGFR mutation-positive advanced non-small cell lung cancer have better overall survival when treated with gefitinib or chemotherapy than patients whose tumors do not carry such mutations.

At the 35th Congress of the European Society for Medical Oncology (ESMO), Professor Chih-Hsin James Yang from National Taiwan University Hospital reported final overall survival results from the IPASS study.

The IPASS study --whose primary endpoint results were presented at the ESMO 2008 Congress in Stockholm-- compared progression-free survival and overall survival in 1217 East Asian patients with advanced non-small cell lung cancer treated with first-line gefitinib or carboplatin and paclitaxel. The patients in the study were all never-smokers or light ex-smokers.

The matured results reported at the ESMO Congress this year show a median overall survival of 18.8 months in patients who began treatment with gefitinib, while survival in the chemotherapy group was 17.4 months. The difference between these groups was not statistically significant.

The lack of difference significance between the treatment groups might be explained by the fact that a high proportion of the patients received the alternative study treatment or other therapies after progression from first-line treatment, Prof Yang noted.

In the gefitinib arm, 60% of patients received subsequent platinum-based combination chemotherapy, while 51% of patients in the chemotherapy arm received subsequent gefitinib or erlotinib treatment. Only 31% of patients in the gefitinib arm and 38% in the paclitaxel and carboplatin arm did not receive further systemic anticancer treatment.

Among patients whose tumor tissue contained EGFR mutations, median survival was 21.6 months for the 132 patients who received first-line gefitinib and 21.9 months for the 129 given combination chemotherapy. This was compared to 11.2 months median survival for the 91 gefitinib patients whose tumors tested negative for EGFR mutations, and 12.7 months for EGFR negative patients treated with chemotherapy.

"Mature overall survival data show that patients with EGFR mutation-positive advanced non-small cell lung cancer had better outcomes than patients with EGFR mutation-negative disease, regardless of which treatment arm they were in," Prof Yang said.

"The results of this study demonstrate that EGFR mutation status is a predictive factor for better progression-free survival with gefitinib. These data add to the growing body of evidence that different types of non-small cell lung cancer exist, requiring a range of different therapies."

"It's important to consider very carefully when choosing a first-line treatment for advanced non-small cell lung cancer, as many patients in clinical practice will not receive further active treatments," Prof Yang added.

Dr Marina Garassino of Fatebenefratelli Hospital in Milan commented: "The results of this important study show us that it is fundamental to tailor each patient's treatment on the basis of genetic characteristics. In particular, this study illustrated that the presence of a particular mutation in the EGFR gene may confer a great sensitivity to gefitinib. In patients with these characteristics, gefitinib gives dramatic and prolonged responses."

"This study seems to give us negative results about the increase of overall survival, but these negative results must be carefully interpreted. They are due to the fact that the majority of patients received gefitinib as second choice," Dr Garassino said. "In fact, in patients with EGFR mutations, this drug produces important results after progression of the tumor with chemotherapy. Therefore, the treatment with gefitinib in patients with EGFR-mutated tumors in the two groups of the trial may have masked the increase of survival."

Source: ESMO