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Clinical Trial
. 2014 Jan 7;110(1):55-62.
doi: 10.1038/bjc.2013.721. Epub 2013 Nov 21.

First-line Gefitinib in Caucasian EGFR Mutation-Positive NSCLC Patients: A phase-IV, Open-Label, Single-Arm Study

Free PMC article
Clinical Trial

First-line Gefitinib in Caucasian EGFR Mutation-Positive NSCLC Patients: A phase-IV, Open-Label, Single-Arm Study

J-Y Douillard et al. Br J Cancer. .
Free PMC article


Background: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

Treatment: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples.

Results: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7).

Conclusion: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.


Figure 1
Figure 1
Patient disposition flow diagram. aAll screened patients. Used to calculate the correlation between clinical characteristics and tumour EGFR mutation status and the comparison of EGFR mutation status between tumour DNA and plasma-derived circulating free DNA. bOne patient of EGFR mutation-positive-ineligible status was treated in error and included in the evaluable-for-safety population. A total of 107 patients therefore started study treatment. cFull analysis set population. Used to summarise efficacy data, and for the comparison of EGFR mutation status in plasma and tumour samples. dNumber of patients with EGFR mutation-positive tumours (n=118) used as the denominator for the percentage calculation. eNumber of patients started on treatment (n=107) used as the denominator for the percentage calculation. Abbreviation: EGFR=epidermal growth factor receptor.
Figure 2
Figure 2
Kaplan–Meier curves for (A) PFS and (B) OS (FAS population). Patients without a PFS event at the time of the primary analysis were censored at the date of their last objective tumour assessment. Abbreviations: CI=confidence interval; NC=not calculable; OS=overall survival; PFS=progression-free survival.

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