Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a west Japan thoracic oncology group trial (WJTOG0203).
PURPOSE Gefitinib is a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase. We conducted a phase III trial to evaluate whether gefitinib improves survival as sequential therapy after platinum-doublet chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Chemotherapy-naïve patients with advanced stage (IIIB/IV) NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate organ function were randomly assigned to either platinum-doublet chemotherapy up to six cycles (arm A) or platinum-doublet chemotherapy for three cycles followed by gefitinib 250 mg orally once daily, until disease progression (arm B). Patients were stratified by disease stage, sex, histology, and chemotherapy regimens. The primary end point was overall survival; secondary end points included progression-free survival, tumor response, safety, and quality of life. Results Between March 2003 and May 2005, 604 patients were randomly assigned. There was a statistically significant improvement in progression-free survival in arm B (hazard ratio [HR], 0.68; 95% CI, 0.57 to 0.80; P < .001); however, overall survival results did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.03; P = .11). In an exploratory subset analysis of overall survival by histologic group, patients in arm B with adenocarcinoma did significantly better than patients in arm A with adenocarcinoma (n = 467; HR, 0.79; 95% CI, 0.65 to 0.98; P = .03). CONCLUSION This trial failed to meet the primary end point of OS in patients with NSCLC. The exploratory subset analyses demonstrate a possible survival prolongation for sequential therapy of gefitinib, especially for patients with adenocarcinoma.
Takeda
Koji
K
2-13-22 Miyakojimahondohri, Miyakojima-ku, Osaka 534-0021, Japan. kkk-take@ga2.so-net.ne.jp
Hida
Toyoaki
T
Sato
Tosiya
T
Ando
Masahiko
M
Seto
Takashi
T
Satouchi
Miyako
M
Ichinose
Yukito
Y
Katakami
Nobuyuki
N
Yamamoto
Nobuyuki
N
Kudoh
Shinzoh
S
Sasaki
Jiichiro
J
Matsui
Kaoru
K
Takayama
Koichi
K
Kashii
Tatsuhiko
T
Iwamoto
Yasuo
Y
Sawa
Toshiyuki
T
Okamoto
Isamu
I
Kurata
Takayasu
T
Nakagawa
Kazuhiko
K
Fukuoka
Masahiro
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000208:ethnology / Q000401:mortality; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000208:ethnology / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000208:ethnology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin; D000077156:Gefitinib