Maintenance gefitinib in unresected Stage III NSCLC is associated with inferior survival

The SWOG 0023 study comparing maintenance gefitinib after initial chemoradiotherapy and three cycles of docetaxel in unresectable Stage III NSCLC found a median overall survival of 23 months in the treatment arm compared to 35 months with placebo.This study was presented by Dr Karen Kelly who began by outlining the rationale for the use of gefitinib and its effect in NSCLC. She described the good results of an earlier Phase II study (SWOG 9504) of combined modality therapy using platinum/etoposide with radiotherapy followed by three cycles of docetaxel. They hoped to further improve outcomes with the use of gefitinib.Eligible patients had unresectable Stage III NSCLC, PS 0 -1 and an forced expiratory volume of greater than 2 l (or greater than 0.8 l in the contralateral lung). Those who did not progress during the initial phase were to receive gefitinib 500mg daily or placebo for 5 years. The dose of gefitinib was reduced to 250 mg daily when the results of the IDEAL trials were released. They intended to enroll 840 patients and randomise 642 but the trial was closed early by the Data Safety Management Board after an interim analysis when 243 patients had been randomised. The preliminary results were presented at ASCO in 2005 and a have now been updated with a median follow up of 27 months.The two arms were well balanced except for a slight excess of non-white patients in the placebo arm (14 v 3%). Half had Stage IIIA disease and half PS 0. The gefitinib arm had a median overall survival of 23 months compared with 35 months in the placebo arm (p=0.013); one year survival was 73% and 81% and two year survival was 46% and 59%. The cause of death was largely disease progression, with only 2% due to gefitinib, 4% from docetaxel and 2% from the combined modality treatment. The volume of lung treated was an important prognostic factor with those having a V20 of >35% having a median survival of 12 v 24 months (p = 0.0006). Non-white patients did better than the white group on subset analysis.Dr Kelly concluded by looking at possible reasons for the poor outcome in the experimental arm. Although the actual reason is unclear, it may be related to changes in epiderman growth factor receptor (EGFR) expression after chemotherapy and radiotherapy. She stated that tyrosine kinase inhibitors targeting EGFR receptors should only be used in the context of a clinical trail and that the core regime used in SWOG 9504 again gave good results.Reference...