LAUSR

Introduction: Type 1 insulin‐like growth factor receptor is deregulated in solid tumors. Cixutumumab, a monoclonal antibody that inhibits the activity of type 1 insulin‐like growth factor receptor, was investigated in combination with pemetrexed/cisplatin in the frontline setting. Methods: In this open‐label, phase II study, patients with stage IV nonsquamous NSCLC and a performance status of 0 to 1 were randomized (1:1) to receive 20 mg/kg cixutumumab, 500 mg/m2 pemetrexed, and 75 mg/m2 cisplatin (cixutumumab [n = 87]) or pemetrexed and cisplatin (control [n = 85]). Eligible patients received pemetrexed‐based maintenance therapy with cixutumumab (cixutumumab arm) or without it (control arm). The primary end point was progression‐free survival. Secondary end points assessed overall survival, objective response rate, and safety. Survival was analyzed by the Kaplan‐Meier method and Cox proportional hazard model. Exploratory correlative analyses were also performed. Results: The mean age of the intent‐to‐treat population (n = 172) was 59 years (range 32–83). Median progression‐free survival was 5.45 months with cixutumumab versus 5.22 months in the control (hazard ratio = 1.15, 95% confidence interval: 0.81–1.61; p = 0.44). Median overall survival was 11.33 months with cixutumumab versus 10.38 months in the control (hazard ratio = 0.93, 95% confidence interval: 0.64–1.36). Objective response rate did not differ between treatments (p = 0.338). Grade 3 or 4 hyperglycemia occurred at a higher rate with cixutumumab than in the control (9.4% versus 1.2%). One death possibly related to cixutumumab occurred. Conclusions: Efficacy was not improved in patients with nonsquamous NSCLC when cixutumumab was added to pemetrexed/cisplatin. Combination therapy was well tolerated and no new safety concerns were reported.