Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
BACKGROUND
Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy.


METHODS
We randomly assigned 230 patients with metastatic, non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxic effects.


RESULTS
In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P=0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated aminotransferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease.


CONCLUSIONS
First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.)
Maemondo
Makoto
M
Miyagi Cancer Center, Miyagi, Japan.
Inoue
Akira
A
Kobayashi
Kunihiko
K
Sugawara
Shunichi
S
Oizumi
Satoshi
S
Isobe
Hiroshi
H
Gemma
Akihiko
A
Harada
Masao
M
Yoshizawa
Hirohisa
H
Kinoshita
Ichiro
I
Fujita
Yuka
Y
Okinaga
Shoji
S
Hirano
Haruto
H
Yoshimori
Kozo
K
Harada
Toshiyuki
T
Ogura
Takashi
T
Ando
Masahiro
M
Miyazawa
Hitoshi
H
Tanaka
Tomoaki
T
Saijo
Yasuo
Y
Hagiwara
Koichi
K
Morita
Satoshi
S
Nukiwa
Toshihiro
T
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017239:Paclitaxel / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D016190:Carboplatin; D066246:ErbB Receptors; D017239:Paclitaxel; D000077156:Gefitinib