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)

Abstract

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.

Use of the Epidermal Growth Factor Receptor Inhibitors Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Icotinib in the Treatment of Non-Small-Cell Lung Cancer: A Systematic Review

“…One Japanese trial compared 6 cycles of a platinum doublet with 3 cycles of a platinum doublet followed by gefitinib until progression. A significant improvement in pfs was observed, but no significant improvement in os 105 . A second trial compared bevacizumab plus erlotinib with bevacizumab alone in patients treated with 4 cycles of carboplatin, paclitaxel, and bevacizumab.…”

The role of maintenance pemetrexed in the treatment of non-small-cell lung cancer

“…21 There was no significant difference in OS, the primary end point (13.7 vs 12.9 months; P = 0.10); however, median PFS was statistically significantly prolonged in the gefitinib arm (HR = 0.68; P , 0.001). On subset analysis, patients having maintenance gefitinib with adenocarcinoma did significantly better than patients with adenocarcinoma having just chemotherapy (HR = 0.79; P = 0.03).…”

Improving Outcomes in Advanced Lung Cancer : Maintenance Therapy in Non-Small-Cell Lung Carcinoma = تحسين النتائج في سرطان الرئة المتقدم : العلاج المستدام في سرطان الرئة ذي الخلية غير الصغيرة

“…43 The gefitinib arm revealed improvement in PFS (P = 0.001) with a trend towards improvement in OS. Subset analyses showed doubling in median OS in non-smokers compared to smokers as well as in the adenocarcinoma subtypes in the gefitinib maintenance arm.…”