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 (WJTOG

Abstract

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. No significant financial relationships to disclose.