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