The IPASS study

Design

IPASS (IRESSA Pan-ASia Study) was an open label, randomised, parallel-group study that assessed the efficacy, safety and tolerability of IRESSA versus doublet chemotherapy (carboplatin/paclitaxel) as 1st line treatment in a clinically selected population of patients from Asia. The primary endpoint of IPASS was PFS (progression free survival - the length of time a patient lives without their tumour progressing), with the objective of demonstrating that IRESSA was non-inferior to doublet chemotherapy (carboplatin/paclitaxel).¹

The study enrolled a selected population of 1,217 patients in Asia with advanced NSCLC who had not received prior chemotherapy for advanced disease, whose tumours were of adenocarcinoma histology and who had either never smoked, or were former light smokers (ceased smoking at least 15 years ago and <= 10 pack-years exposure). These were the patients who had shown the most benefit in the ISEL trial 2. 

Results

For the first time a targeted monotherapy demonstrated significantly longer PFS than doublet chemotherapy: IPASS results demonstrated superior PFS compared with doublet chemotherapy in the overall population of clinically selected patients with advanced NSCLC in Asia (Hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.65 to0.85, p<0.0001). 

The EGFR mutation status of a patient’s tumour was a strong predictor of benefit with IRESSA or chemotherapy. Pre-planned sub-group analyses showed that PFS was significantly longer for IRESSA than doublet chemotherapy in patients with EGFR mutation positive tumours (HR 0.48, 95% CI 0.36 to 0.64, p<0.0001), and significantly longer for doublet chemotherapy than IRESSA in patients with EGFR mutation negative tumours (HR 2.85, 95% CI 2.05 to 3.98, p<0.0001).

IRESSA also demonstrated a more favourable tolerability profile and superior quality of life improvement rates for patients versus doublet chemotherapy. 

For secondary endpoints, ORR was superior for IRESSA in the overall population (43% vs. 32%; p=0.0001); for patients with EGFR mutation positive tumours, ORR was superior for IRESSA (71.2% vs 47.3% for IRESSA and carboplatin/paclitaxelrespectively, p=0.0001), and for patients with EGFR mutation negative tumours, ORR was superior for doublet chemotherapy (1.1% (one patient) vs 23.4% for IRESSA and carboplatin/paclitaxel respectively, p=0.0013).

Safety

The safety profile of IRESSA was generally consistent with its prescribing information, previous IRESSA studies in the relapsed setting, and underlying disease. The most commonly reported adverse events with IRESSA are mild to moderate rash and diarrhoea.

References

1. Mok TS et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. New Engl J Med 2009; 361: 947-957.

2. Thatcher N. et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet; 366(9496):1527-1537.