A double-blind, randomised, placebo-controlled phase III intergroup study of gefitinib in patients with advanced...

EORTC study 08021/ILCP 01/03 evaluated the role of consolidation gefitinib, an oral tyrosine kinase inhibitor (TKI), administered in patients with advanced non-small cell lung cancer (NSCLC), not progressing following standard 1st-line chemotherapy.

Patients with advanced NSCLC, not-progressing after four cycles of platinum-based chemotherapy, were randomised to receive either gefitinib 250mg/d or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival (OS). Secondary end-points were progression-free survival (PFS) and toxicity. The study was powered to detect a 28% increase in OS from a median of 11-14.1months (HR=0.78) and planned to randomise 598 patients to observe 514 deaths.

After inclusion of 173 patients, the trial was prematurely closed due to low accrual. Baseline characteristics for gefitinib (n=86) and placebo (n=87) arms were well balanced. After a median follow up of 41months, the difference in median OS in the gefitinib and placebo arms was not statistically significant (10.9 and 9.4months, HR 0.83 [95% confidence interval (95% CI) 0.60-1.15]; p=0.2). The difference in median PFS significantly favoured gefitinib (4.1 and 2.9months, HR=0.61, [95% CI 0.45, 0.83]), p=0.0015). Adverse events reported in more than 10% of patients were rash (47% with gefitinib versus 13% with placebo) and diarrhoea (34% with gefitinib versus13% with placebo).

Despite its premature closure, this trial confirms previous evidence that consolidation gefitinib is safe and improves PFS. However, no difference in OS was observed in this study (NCT00091156).