By Chris Berrie
BERLIN -- October 2, 2009 -- Gefitinib has a favourable toxicity profile and shows significant survival benefits over carboplatin/paclitaxel in first-line treatment of patients with non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations, according to a study presented here at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO).
"The selection by EGFR mutations seemed to be a superior approach based on the results of our phase 2 study," said Akira Inoue, MD, Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan, on September 22.
For the phase 3 study, 230 chemotherapy-naïve patients aged 20 to 75 years with NSCLC (stage IIIb/IV) and sensitive EGFR mutations were randomised to standard chemotherapy of carboplatin area under curve 6 plus paclitaxel 200 mg/m2 in 21-day cycles or to gefitinib 250 mg/day. Patient baseline characteristics were similar between groups.
For the present interim analysis, performed at the end of May 2009, the intent-to-treat population consisted of 98 patients in the gefitinib arm and 100 patients in the carboplatin/paclitaxel arm.
Due to the significantly longer progression-free survival (PFS) seen in patients receiving gefitinib compared with carboplatin/paclitaxel (10.4 vs 5.5 months; P < .001), the Independent Data Safety Monitoring Committee recommended terminating accumulation of patients at the end of May 2009.
Overall response rate was also greater in patients receiving gefitinib (74%), compared with carboplatin/paclitaxel (29%; P < .001).
In an analysis of PFS according to Cox proportional hazard models, as well as the treatment arms, the only other significant factor seen was gender (P = .002).
A search for effects related to EGFR mutation status did not show any significant differences in response rates for PFS between the deletion and the L858R mutation (response rate, 80% vs 72%; median PFS, 10.9 vs 10.0 months).
However, as Dr. Inoue noted, with the patients who had completed their first-line treatment, 73% crossed over from gefitinib to carboplatin/paclitaxel, and 94% of the carboplatin/paclitaxel arm crossed over to gefitinib.
This high crossover rate may also have affected overall survival, where, despite a trend in the median survival times of 23.6 months and 28.0 months for carboplatin/paclitaxel and gefitinib treatments, respectively, no significant difference was seen (P = .354). This provided 2-year survival rates of 45% and 61%, respectively, again showing a trend in favour of gefitinib.
Haematological toxicities were all significantly greater for carboplatin/paclitaxel, over gefitinib. For nonhaematological toxicities, these showed several differences across the treatment arms, with gefitinib showing a relatively favourable toxicity profile.
Dr. Inoue noted that in terms of the risk-benefit balance, gefitinib should be considered as the standard first-line treatment for patients with advanced NSCLC with sensitive EGFR mutations. "Testing for EGFR mutations will be an essential step in guiding the decision for NSCLC treatment, and should become standard practice globally," he added.
[Presentation title: A Randomised Phase III Study Comparing Gefitinib With Carboplatin/Paclitaxel for the First-Line Treatment of Non-Small-Cell Lung Cancer With Sensitive EGFR Mutations: NEJ002 Study. Abstract 9LBA]
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