Journal Article

Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial

Wu, Yi-Long, Douillard, Jean-Yves, Gervais, Radj, Hirsh, Vera, Reck, Martin, Li, Long-Yun, Lippman, Scott M, Armour, Alison A, Lowe, Elizabeth S, Sun, Yan, Østerlind, Kell, Mok, Tony, Shepherd, Frances A, Socinski, Mark A, Liao, Mei-Lin, Kim, Edward S, Sellers, Mark V, Watkins, Claire L

2008

Overview

Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy. We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer who had been pretreated with platinum-based chemotherapy. We undertook an open-label phase III study with recruitment between March 1, 2004, and Feb 17, 2006, at 149 centres in 24 countries. 1466 patients with pretreated (≥one platinum-based regimen) advanced non-small-cell lung cancer were randomly assigned with dynamic balancing to receive gefitinib (250 mg per day orally; n=733) or docetaxel (75 mg/m 2 intravenously in 1-h infusion every 3 weeks; n=733). The primary objective was to compare overall survival between the groups with co-primary analyses to assess non-inferiority in the overall per-protocol population and superiority in patients with high epidermal growth factor receptor (EGFR)-gene-copy number in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00076388. 1433 patients were analysed per protocol (723 in gefitinib group and 710 in docetaxel group). Non-inferiority of gefitinib compared with docetaxel was confirmed for overall survival (593 vs 576 events; hazard ratio [HR] 1·020, 96% CI 0·905–1·150, meeting the predefined non-inferiority criterion; median survival 7·6 vs 8·0 months). Superiority of gefitinib in patients with high EGFR-gene-copy number (85 vs 89 patients) was not proven (72 vs 71 events; HR 1·09, 95% CI 0·78–1·51; p=0·62; median survival 8·4 vs 7·5 months). In the gefitinib group, the most common adverse events were rash or acne (360 [49%] vs 73 [10%]) and diarrhoea (255 [35%] vs 177 [25%]); whereas in the docetaxel group, neutropenia (35 [5%] vs 514 [74%]), asthenic disorders (182 [25%] vs 334 [47%]), and alopecia (23 [3%] vs 254 [36%]) were most common. INTEREST established non-inferior survival of gefitinib compared with docetaxel, suggesting that gefitinib is a valid treatment for pretreated patients with advanced non-small-cell lung cancer. AstraZeneca.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Aged / Aged, 80 and over / Antineoplastic Agents - adverse effects / Antineoplastic Agents - therapeutic use / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - mortality / Chemotherapy / Female / Humans / Internal Medicine / Lung cancer / Lung Neoplasms - drug therapy / Lung Neoplasms - mortality / Lung Neoplasms - pathology / Male / Middle Aged / Ovarian cancer / Platinum / Quality of Life / Quinazolines - adverse effects / Quinazolines - therapeutic use / Receptor, Epidermal Growth Factor - genetics / Studies / Survival / Survival Analysis / Taxoids - adverse effects / Taxoids - therapeutic use