Randomized phase III study of platinum-doublet chemotherapy followed by gefitinib versus continued platinum-doublet chemotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): Results of West Japan Thoracic Oncology Group trial (WJTOG0203)
T. Hida, I. Okamoto, T. Kashii, M. Satouchi, Y. Ichinose, N. Katakami, M. Ando, T. Kurata, K. Nakagawa and M. Fukuoka
Aichi Cancer Ctr, Nagoya, Japan; Kinki University School of Medicine, Osaka-Sayama, Japan; Osaka City General Hospita1, Osaka, Japan; Hyogo Cancer Center, Akashi, Japan; National Kyusyu Cancer Center, Fukuoka, Japan; Institute of Biomedical Research and Innovation, Kobe, Japan; Kyoto University School of Public Health, Kyoto, Japan; Osaka Medical College, Takatsuki, Japan; Kinki University School of Medicine Sakai Hospital, Sakai, Japan
LBA8012
Background: Gefitinib is a small molecule inhibitor of the EGFR tyrosine kinase. When combined with chemotherapy, no survival gain was observed compared to chemotherapy alone (INTACT I and II). We have conducted a randomized phase III trial to evaluate whether gefitinib improves survival as maintenance therapy after platinum-doublet chemotherapy in pts with advanced NSCLC.
Methods: Chemotherapy-naïve pts with advanced stage (IIIB/IV) NSCLC, ECOG PS of 0–1, and adequate organ functions were randomized to either, A) platinum-doublet chemotherapy (Carboplatin AUC 6+Paclitaxel 200mg/m2 day1 Q3w, Cisplatin 80mg/m2 day1+Irinotecan 60mg/m2 day1,8,15 Q4W, Cisplatin 80mg/m2 day1+Vinorelbine 25mg/m2 day1,8 Q3W, Cisplatin 80mg/m2 + Docetaxel 60mg/m2 day1 Q3W, or Cisplatin 80mg/m2 day1+Gemcitabine 1000mg/m2 day1, 8 Q3W) up to 6 cycles or B) platinum-doublet chemotherapy for 3 cycles followed by gefitinib 250 mg orally once daily. Pts were stratified by disease stage, gender, histology and chemotherapy regimens. The primary endpoint was overall survival (OS); secondary endpoints include progression-free survival (PFS), response rate (RR), safety and QOL. A sample size of 300 pts per group was estimated on the basis of a projected median survival of 9 months (m) in arm A and 11.4 m in arm B, with a power of 80% at 0.05 two-sided alpha to compare both group.
Results: 603 pts were randomized between March 2003 and May 2005, and pt characteristics were equally distributed between arms. There was a statistically significant improvement in PFS (HR, 0.68; 95% CI, 0.57–0.80; P<0.001) in arm B; however, OS result did not reach statistical significance (P=0.10). In a pre-specified analysis of OS by histologic groups, arm B had significantly better OS than arm A in adenocarcinoma histology (n=467; HR, 0.79; 95% CI, 0.65–0.98; P=0.03).
Conclusions: These results demonstrate a possible clinical benefit for maintenance therapy of gefitinib, especially in adenocarcinoma histology.
