The trial was designed to determine whether maintenance therapy with gefitinib would improve survival in patients who had undergone treatment with cisplatin-etoposide plus radiation, followed by consolidation therapy with docetaxel.

Previous studies showed that cisplatin-etoposide followed by docetaxel consolidation therapy could lead to median survival rates of 26% and overall survival of 29%. Past studies also showed that gefitinib produced significant benefits in 10% to 20% of patients with advanced NSCLC.

Of more than 600 patients in the original SWOG 0023 cohort, 255 were eventually deemed to be "nonprogressors" (ie, their disease remained stable after treatment with cisplatin-etoposide plus radiation therapy, followed by 3 courses of docetaxel consolidation). These patients were then randomized to maintenance therapy with either gefitinib (n = 124) or placebo (n = 131).

The study was designed to demonstrate 33% superiority in survival in the study arm over the control arm, which would have a projected survival of 21 months.

However, the study data safety and monitoring committee in a meeting in April 2005 determined that the study did not meet these endpoints and that the endpoints were impossible to reach. As a result, the study was terminated, Dr Kelly said in her presentation.

At a mean of 2 years after randomization, the progression-free survival was a nonsignificant 11 months in the gefitinib arm compared with 10 months in the placebo arm.

Overall survival was 29 months in the placebo arm compared with 19 months in the study arm, which represents 43 events among patients treated with gefitinib compared with 32 events among patients receiving the placebo.

There were no statistically significant differences in outcomes among patients receiving either gefitinib 250 mg (n = 81) or 500 mg (n = 43).

The majority of patients in this study died from disease progression, Dr. Kelly explained, noting that adverse effects were not severe in most cases and were not unexpected. Two patients in the gefitinib arm developed grade 3 pneumonitis, and 1 developed grade 4 pneumonitis, which is in keeping with what has been seen in other studies.

Dr. Kelly said the outcome was "puzzling" but the results are being actively investigated and analyzed for epidermal growth factor receptor as well as K-ras mutations.

For the time being, she added, the core treatment seen in the first part of this study -- cisplatin-etoposide plus radiation therapy, followed by docetaxel consolidation therapy -- should be considered the standard of treatment for patients with unresectable advanced non-small-cell lung cancer.


[Presentation title: Low Incidence of Pneumonitis on SWOG 0023: A Preliminary Analysis of an Ongoing Phase III Trial of Concurrent Chemoradiotherapy Followed by Consolidation Docetaxel and Iressa/Placebo Maintenance in Patients With Inoperable Stage III Non-Small-Cell Lung Cancer. Abstract 7058]

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