Combined survival analysis of prospective clinical trials of gefitinib for non-small cell lung cancer with EGFR mutations.
OBJECTIVE
Somatic mutations of the epidermal growth factor receptor (EGFR) gene are associated with an increased response to gefitinib in patients with non-small cell lung cancer. We have examined the impact of gefitinib on progression-free survival and overall survival in patients with EGFR mutation-positive non-small cell lung cancer.


METHODS
We searched for all clinical trials that prospectively evaluated the efficacy of gefitinib for advanced non-small cell lung cancer with EGFR mutations in Japan. We did a combined analysis based on individual patient data from the identified trials.


RESULTS
Seven eligible trials were identified for a total of 148 non-small cell lung cancer patients with EGFR mutations. The overall response rate to gefitinib was 76.4% [95% confidence interval (95% CI), 69.5-83.2]. The median progression-free survival and overall survival were 9.7 months (95% CI, 8.2-11.1) and 24.3 months (95% CI, 19.8-28.2), respectively. Good performance status and chemotherapy-naïve status were significantly associated with a longer progression-free survival or overall survival. Of the 148 patients, 87 received gefitinib as a first-line therapy, whereas 61 received systemic chemotherapy before gefitinib treatment. The median progression-free survival after the start of first-line therapy was significantly longer in the gefitinib-first group than in the chemotherapy-first group (10.7 versus 6.0 months; P < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (27.7 versus 25.7 months; P = 0.782).


CONCLUSIONS
Gefitinib monotherapy confers substantial clinical benefit in terms of progression-free survival and overall survival in non-small cell lung cancer patients with EGFR mutations. Randomized trials comparing chemotherapy with gefitinib as a first-line treatment are warranted in such patients.
Morita
Satoshi
S
Department of Biostatistics and Epidemiology, Yokohama City University Medical Center, Yokohama, Japan.
Okamoto
Isamu
I
Kobayashi
Kunihiko
K
Yamazaki
Koichi
K
Asahina
Hajime
H
Inoue
Akira
A
Hagiwara
Koichi
K
Sunaga
Noriaki
N
Yanagitani
Noriko
N
Hida
Toyoaki
T
Yoshida
Kimihide
K
Hirashima
Tomonori
T
Yasumoto
Kosei
K
Sugio
Kenji
K
Mitsudomi
Tetsuya
T
Fukuoka
Masahiro
M
Nukiwa
Toshihiro
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib