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 ... -  《-》

First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations.

Sequist LV ，Martins RG ，Spigel D ，Grunberg SM ，Spira A ，Jänne PA ，Joshi VA ，McCollum D ，Evans TL ，Muzikansky A ，Kuhlmann GL ，Han M ，Goldberg JS ，Settleman J ，Iafrate AJ ，Engelman JA ，Haber DA ，Johnson BE ，Lynch TJ ... -  《-》

Gefitinib as first-line treatment in elderly epidermal growth factor receptor-mutated patients with advanced lung adenocarcinoma: results of a Nagano Lung Cancer Research Group study.

Efficacy of first-line gefitinib for elderly epidermal growth factor receptor mutated patients with lung adenocarcinoma is uncertain. This study was aimed to investigate efficacy of gefitinib for such population. The primary endpoint was response rate (RR) and at least 12 cases were needed. Overall RR was 59% (95% confidence interval, 33%-81%) and first-line gefitinib was effective for elderly patients. Feasibility of gefitinib therapy in elderly patients with non-small-cell lung cancer is uncertain. This phase II study aimed to investigate the efficacy and usefulness of gefitinib therapy as a first-line treatment for elderly patients who have advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. We enrolled chemotherapy-naïve advanced lung adenocarcinoma patients aged 75 years or older. Patients were administered gefitinib (250 mg) once daily until progression or unacceptable toxicity. The primary endpoint was response rate (RR), and secondary endpoints were disease control rate (DCR; defined as complete response [CR] plus partial response [PR] plus stable disease [SD]), progression-free survival (PFS), overall survival (OS), and toxicity profile. Between April 2008 and November 2009, 17 lung adenocarcinoma patients were enrolled. Overall RR was 59% (95% confidence interval [CI]: 33% to 81%), with 2 patients achieving CR and 8 PR. SD was noted in 5 patients, and DCR was 88% (95% CI: 62% to 98%). Median PFS was 12.9 months (95% CI: 2.2 to 23.6 months), and median OS had not yet been reached. Major grade 3 toxicities were skin rash (12%) and increased levels of aspartate aminotransferase or alanine aminotransferase (18%). First-line treatment with gefitinib was effective and well-tolerated in elderly patients with EGFR mutations.

Asami K ，Koizumi T ，Hirai K ，Ameshima S ，Tsukadaira A ，Morozumi N ，Morikawa A ，Atagi S ，Kawahara M ... -  《-》

Good response to gefitinib in lung adenocarcinoma of complex epidermal growth factor receptor (EGFR) mutations with the classical mutation pattern.

Wu SG ，Chang YL ，Hsu YC ，Wu JY ，Yang CH ，Yu CJ ，Tsai MF ，Shih JY ，Yang PC ... -  《-》

Effect of gefitinib challenge to initial treatment with non-small cell lung cancer.

This study was conducted to assess the efficacy and toxicity of gefitinib as first line treatment in patients with advanced non-small-cell lung cancer (NSCLC). Tumor tissue, derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve patients with advanced (stage IIIB, IV and recurrent) NSCLC. Tumor genomic DNA underwent direct sequencing for EGFR exons 18, 19, 20 and 21. Sixty-one patients received 250mg of gefitinib daily until disease progression or unacceptable toxicity. Out of 61 patients, 26 patients (42.6%) were EGFR mutations and 11 patients were wild type, 24 patients were status unknown. One patient achieved complete remission (CR). While 17 patients achieved partial remission (PR) and 23 experienced stable disease (SD). There were 20 patients developed progressive disease (PD). The tumor response rate and disease control rate was 29.5 and 67.2%, respectively, and symptom remission rate was 66.7% as well. Median remission time was 9 days. Median over survival time was 13.0 months. Median progression-free survival time was 5.0 months. The MST of patients with EGFR mutation was 17.0 months, while the MST of patients with EGFR status unknown or wild type was 11.0 months. The PFS of patients with EGFR mutation was 9.0 months and it in EGFR status unknown or wild type was 2.5 months .The most common toxicity included rash (54.1%) and diarrhea (31.1%). Dehydration and pruritus of skin was observed in 31.1 and 26.2% of the patients respectively. Hepatic toxicity occurred in 8.2% of patients and oral ulceration occurred in six patients (9.8%). Single agent treatment with gefitinib is effective in patients with advanced NSCLC, especially in patients with EGFR mutation, and well tolerated in Chinese patients.

Chen X ，Li W ，Hu X ，Geng Y ，Wang R ，Yin Y ，Shu Y ... -  《-》