An Open-Label, Multicenter, Randomized, Phase II Study of Cisplatin and Pemetrexed With or Without Cixutumumab...

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.

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.

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.

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.