Randomized phase II study of sequential carboplatin/paclitaxel (CP) and gefitinib (G) in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC): Final results

Abstract

8069 Background: G has been shown to exhibit antitumor activity against NSCLC, however, the optimal timing of its administration remains unclear. We conducted a randomized phase II study of CP followed by G or G followed by CP in chemotherapy-naïve advanced NSCLC patients in order to select the candidate arm for a subsequent phase III study. Methods: Chemotherapy-naïve patients with histologically or cytologically confirmed NSCLC, stage IIIB or IV, aged between 20 to74 years, performance status 0–1, were randomized to either Arm A (carboplatin (AUC 6, day 1) plus paclitaxel (200 mg/m2, day 1) every 3 weeks for 4 courses followed by daily G (250 mg/day)) or Arm B (daily G until disease progression followed by CP every 3 weeks for 4 courses). The primary endpoint was overall survival, and the planned sample size for this randomized phase II study was 96 patients (Liu’s selection design for pilot studies on survival, Biometrics 49: 391–398, 1993). Results: From June 2003 to October 2005, 97 patients were enrolled, and 96 of these patients were treated in this study. Forty-nine patients (males/females: 28/21, median age: 63 years, adeno/non-adeno: 43/6, stageIII/IV: 11/38, smoker/non-smoker: 27/22) were randomized to Arm A and 48 patients (males/females: 28/20, median age: 61 years, adeno/non-adeno: 42/6, stageIII/IV: 11/37, smoker/non-smoker: 28/20) to Arm B. The response rate to CP in Arm A was 32.7% (16/49), and that to G in Arm B was 29.8% (14/47). The median survival times were 18.8 months and 17.2 months, and the 1-year survival rates were 61.2% and 68.1% in Arm A and arm B, respectively. One patient had died of treatment-related perforative peritonitis and two patients had developed interstitial lung disease. Conclusions: Although overall survival is similar in both arms, from both survival curves we select CP followed by G as the experimental arm for a subsequent phase III study. No significant financial relationships to disclose.