Phase III studies including our NEJ002 have clearly shown that first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide a longer progression-free survival (PFS) than does standard chemotherapy to patients with metastatic NSCLC harboring EGFR mutation. Although previous randomized trials failed to show a benefit for EGFR TKIs plus chemotherapy in unselected NSCLC patients, this concept has not been prospectively evaluated for NSCLC with EGFR mutations.Methods
This multi-center randomized phase II trial was designed to investigate an efficacy and safety of the combined regimen with gefitinib plus chemotherapy and to select a proper regimen for phase III evaluation in advanced NSCLC harboring EGFR mutations. Main eligibility criteria stipulated chemotherapy-naive, stage IIIB, IV, or relapsed NSCLC (non-squamous histology) with EGFR mutations, over 20 and under 75 years old, PS 0-1, and adequate organ functions. The primary end point is PFS. The arm with the superior PFS is to be selected provided that it meets a minimum of 12 months. Secondary end points include response rate, overall survival, and safety. Eighty patients are randomly assigned to receive either concurrent gefitinib plus platinum-based doublet chemotherapy followed by maintenance (C group) or alternation of gefitinib and chemotherapy also followed by maintenance (A group). Patients in C group receive concurrent gefitinib (250 mg daily) plus carboplatin (AUC = 6, day 1) /pemetrexed (500 mg/m2, day 1) of 3-week cycle for 6 cycles, followed by concurrent gefitinib and pemetrexed maintenance until disease progression. Patients in A group initially receive gefitinib (days 1 to 56) and then carboplatin/pemetrexed (day 57 and 79); the cycle is repeated for 3 cycles, followed by sequential gefitinib and pemetrexed maintenance. This study is ongoing and has recruited 78 pateints to date.