Data from the IPASS study showed that overall survival ( OS ) was similar, with no significant difference, between Gefitinib ( Iressa ) and Carboplatin / Paclitaxel ( doublet chemotherapy ) in the overall population ( HR=0.90; p=0.11, median OS 18.8 vs 17.4 months ).
Neither was there a significant difference between treatment arms for overall survival in the subgroups defined by EGFR mutation status: EGFR mutation-positive patients ( HR=1.00; median OS 21.6 vs 21.9 months ); EGFR mutation-negative patients ( HR=1.18; median OS 11.2 vs 12.7 months ); and patients whose EGFR mutation status was unknown ( HR=0.82; median OS 18.9 vs 17.2 months ).

The IPASS OS data confirmed 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.

Gefitinib is an EGFR-TKI ( epidermal growth factor receptor tyrosine kinase inhibitor ), which targets and blocks the activity of the EGFR-TK, an enzyme that regulates intracellular signalling pathways implicated in cancer cell proliferation and survival. Growth factor signalling has been identified as a key driver of tumour growth and spread in a wide range of cancers.

IRESSA Pan-ASia Study ( IPASS ) was a Phase III open label, randomised, parallel-group study that assessed the efficacy, safety and tolerability of Gefitinib versus standard doublet chemotherapy ( Carboplatin / Paclitaxel ) as first-line treatment in a clinically selected population of 1,217 patients from Asia.
The patients had advanced NSCLC and had not received prior chemotherapy for advanced disease.
Their tumours were of adenocarcinoma histology.
They had either never smoked, or were former light smokers ( ceased smoking at least 15 years ago and minor than or equal to 10 pack-years exposure ). The primary endpoint was progression-free survival ( PFS ); the secondary endpoints included overall survival, objective response rate, quality of life and safety.

Analysis of the primary endpoint of IPASS in 2008 demonstrated that Gefitinib was superior to Carboplatin / Paclitaxel in terms of progression-free survival in the overall population ( HR 0.74; p<0.001 ).
Further analysis of the data demonstrated that Gefitinib's PFS superiority in the overall population was driven by the effect of Gefitinib versus Carboplatin / Paclitaxel in the subgroup of EGFR mutation-positive patients. In these patients, compared with Carboplatin / Paclitaxel, Gefitinib reduced the risk of progression by 52% ( HR=0.48; p<0.001 ) and median progression-free survival was increased from 6.3 to 9.5 months. In addition, Gefitinib provided significant benefits in objective response rate, quality of life and symptom improvement compared with Carboplatin / Paclitaxel in EGFR mutation-positive patients.

Iressa is approved in the EU for the treatment of patients with locally advanced or metastatic NSCLC with activating mutation of EGFR-TK.

NSCLC is the more common of the two forms of lung cancer. The other is small-cell lung cancer ( SCLC ), which accounts for 15% of cases, whereas NSCLC accounts for approximately 85%.
Approximately 10-15% of NSCLC patients in Europe and 30-35% of NSCLC patients in Asia have EGFR mutation-positive NSCLC.

Source: ESMO Meeting, 2010

XagenaMedicine2010


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