Final Analysis of Landmark IPASS Study Confirms That IRESSA (Gefitinib) is a Valuable Option for the First-Line Treatmen

Mature data from the IPASS study, presented today at the 2010 ESMO congress, showed that overall survival (OS) was similar, with no significant difference, between IRESSA (an EGFR tyrosine kinase inhibitor (TKI)) and carboplatin/paclitaxel (doublet chemotherapy) in the overall population (HR=0.90, 95% CI 0.79-1.02, p=0.11, median OS 18.8 vs. 17.4 months). Neither was there a significant difference between treatment arms for OS in the subgroups defined by EGFR mutation status: EGFR mutation-positive patients (HR=1.00, 95% CI 0.76-1.33, median OS 21.6 vs. 21.9 months); EGFR mutation-negative patients (HR=1.18, 95% CI 0.86-1.63, median OS 11.2 vs. 12.7 months); and patients whose EGFR mutation status was unknown (HR=0.82, 95% CI 0.70-0.96, median OS 18.9 vs. 17.2 months).
The mature IPASS OS data confirm that patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) had better outcomes, regardless of which treatment arm they were in, compared to patients with EGFR mutation-negative disease. Median survival times were around 22 months for EGFR mutation-positive patients, but only 11-12 months for EGFR mutation-negative patients.[1] The majority of EGFR mutation-positive patients in IPASS received an EGFR-TKI at some point as 64% of those randomised to carboplatin/paclitaxel later received an EGFR-TKI as subsequent therapy.
"I believe that progression-free survival is a better endpoint than overall survival for evaluation of treatment effect in the first-line setting," said IPASS investigator, Professor James Yang from National Taiwan University Hospital. "However, the IPASS data show that EGFR mutation-positive patients have better survival outcomes than EGFR mutation-negative patients, regardless of whether they were randomised to IRESSA or chemotherapy. Lung cancer patients should be tested to determine their EGFR mutation status, as EGFR mutation-positive patients benefit from treatment with IRESSA through longer progression-free survival, improved control of their symptoms and better quality of life, compared with doublet chemotherapy. It's important to consider very carefully when choosing a first-line treatment for advanced NSCLC, as many patients in clinical practice will not receive further active treatment".
Analysis of the primary endpoint of IPASS in 2008 demonstrated that IRESSA was superior to carboplatin/paclitaxel in terms of progression-free survival (PFS) in the overall population (HR 0.74, 95% CI 0.65-0.85, p<0.001). Further analysis of the data demonstrated that IRESSA's PFS superiority in the overall population was driven by the effect of IRESSA vs. carboplatin/paclitaxel in the subgroup of EGFR mutation-positive patients. In these patients, compared with carboplatin/paclitaxel, IRESSA reduced the risk of progression by 52% (HR=0.48, 95% CI 0.36-0.64, p<0.001) and median progression-free survival was increased from 6.3 to 9.5 months. In addition, IRESSA provided significant benefits in objective response rate, quality of life and symptom improvement compared with carboplatin/paclitaxel in EGFR mutation-positive patients.
"IPASS is a landmark study, which changed the way the oncology community viewed lung cancer," said Alison Armour, Medical Science Director for AstraZeneca. "It was anticipated that the significant IRESSA progression-free survival benefit may not translate into an overall survival benefit, due to the large amounts of subsequent treatment that patients could have received following disease progression on their randomised first-line treatment. IPASS data reinforce that there should be a move towards recognising that lung cancer is a complex disease with distinct subtypes requiring targeted medicines."
The IPASS data from 2008 formed part of the data package leading to the current indication for IRESSA in Europe.[4] The ESMO Clinical Practice Guidelines for metastatic NSCLC state that first-line treatment with a TKI is an option in patients with tumours harbouring an activating EGFR mutation. IRESSA is currently indicated in Europe for the treatment of patients with EGFR mutation-positive advanced NSCLC. Outside of Europe, IRESSA is licensed in a further 44 countries, labelled indications vary from country to country.