Effect of gefitinib on the survival of patients with recurrence of lung adenocarcinoma after surgery: a retrospective case-matching cohort study.

Patients with lung adenocarcinoma who carry epidermal growth factor receptor (EGFR) gene mutations respond remarkably well to EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib, or erlotinib. However, the effect of EGFR-TKI treatment on the prolongation of overall survival (OS) of these patients remains uncertain, although several recent studies have shown prolongation of progression free survival compared with cytotoxic chemotherapy. A total of 304 patients with lung adenocarcinoma who had postoperative recurrent disease were studied. To eliminate potential biases as possible, the matching of four potential predictive factors of responsiveness to EGFR-TKI led to the identification of 81 pairs of patients (those who were treated with gefitinib and those who were not). A deletion mutation in exon 19 and a point mutation (L858R) in exon 21 of the EGFR gene were also analyzed. We compared the OS between the two groups. OS in the gefitinib group was significantly longer than in the control group (median, 63 vs. 41 months; p = 0.015). EGFR mutations were detected in 65 out of 129 patients (50%) in the whole sample. EGFR mutational status was not an independent prognostic factor of gefitinib benefit; rather, it was a predictive factor. This study strongly suggested that gefitinib treatment improved OS of lung adenocarcinoma patients who had postoperative recurrence, especially those carrying EGFR mutations.

Katayama T ，Matsuo K ，Kosaka T ，Sueda T ，Yatabe Y ，Mitsudomi T ... -  《-》

Comparison of clinical outcomes following gefitinib and erlotinib treatment in non-small-cell lung cancer patients harboring an epidermal growth factor receptor mutation in either exon 19 or 21.

Lim SH ，Lee JY ，Sun JM ，Ahn JS ，Park K ，Ahn MJ ... -  《-》

Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations.

Won YW ，Han JY ，Lee GK ，Park SY ，Lim KY ，Yoon KA ，Yun T ，Kim HT ，Lee JS ... -  《-》

EGFR mutations predict survival benefit from gefitinib in patients with advanced lung adenocarcinoma: a historical comparison of patients treated before and after gefitinib approval in Japan.

Takano T ，Fukui T ，Ohe Y ，Tsuta K ，Yamamoto S ，Nokihara H ，Yamamoto N ，Sekine I ，Kunitoh H ，Furuta K ，Tamura T ... -  《-》

A multicenter phase II study to evaluate the efficacy and safety of gefitinib as first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations.

This study was designed to prospectively evaluate the efficacy and safety of first-line gefitinib treatment in patients with advanced pulmonary adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations and to explore the molecular factors affecting the efficacy of gefitinib. Tumor tissue, derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve pts with advanced (stage IIIB, IV, and recurrent) pulmonary adenocarcinoma. Tumor genomic DNA underwent direct sequencing for EGFR exons 18, 19, 20, and 21. Patients with EGFR mutations received 250 mg of gefitinib daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and tolerability. Out of 147 screened patients, 45 pts (31%) had EGFR mutations and received gefitinib. The most common EGFR mutations were in-frame exon 19 deletions (29 pts, 64%) and L858R point mutation in exon 21 (15 pts, 33%). One patient had atypical mutation of L861Q in exon 21. The ORR was 53.3% (95% CI, 38.6-67.9) and disease control rate (DCR) including stable disease was 86.7%. The median progression free survival (PFS) was 398 days and the median overall survival (OS) was 819 days. Treatment was well tolerated. Grade 3/4 adverse events (AEs) were reported by 6 patients and treatment-related Grade 3 AEs by 3 patients. There were no treatment-related Grade 4 AEs. Exploratory subgroup analysis according to the EGFR mutation subtypes was carried out. The ORR and DCR were higher in patients with exon 19 deletions than those with L858R (62.1% vs 33.3%; P=0.0705 and 96.6% vs 66.7%; P=0.0062, respectively). All 4 patients with progressive disease had a L858R mutation. No secondary resistant mutations such as T790M mutation or insertions in exon 20 were found in those patients. In addition, OS was significantly better in patients with exon 19 deletions than those with L858R (24-month OS rate was 72.1% vs 32.0%, P=0.0148). Gefitinib as the first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations was effective and well tolerated. Subgroup analysis suggests that the benefit from gefitinib treatment was more prominent in patients with the exon 19 deletion mutations (ClinicalTrials.gov number, NCT00344773).

Kim DW ，Lee SH ，Lee JS ，Lee MA ，Kang JH ，Kim SY ，Shin SW ，Kim HK ，Heo DS ... -  《-》