Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or without cixutumumab (IMC-A12) in patients with advanced non-squamous, non-small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3508)

Abstract

Background: Cixutumumab is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type I receptor (IGF-IR) that can potentially reverse resistance and enhance the efficacy of chemotherapy.Methods: Bevacizumab-eligible patients with stage IV or recurrent non-squamous, non-small cell lung cancer (NSCLC) and good performance status were randomized to receive standard doses of paclitaxel, carboplatin, and bevacizumab to a maximum of 6 cycles followed by bevacizumab maintenance (CPB) until progression (arm A) or CPB plus cixutumumab 6 mg/kg IV weekly (arm B).Results: Of 175 patients randomized, 153 were eligible and treated (78 in arm A; 75 in arm B). The median progression-free survival was 5.8 months (95% CI, 5.4-7.1) in arm A vs. 7 months (95% CI, 5.7-7.6) in arm B (p = 0.33); hazard ratio 0.92 (95% CI, 0.65-1.31). Objective response was 46.2% vs. 58.7% in arm A vs. arm B (p = 0.15). The median overall survival was 16.2 months in arm A vs. 16.1 months in arm B (p = 0.95). Grade 3/4 neutropenia and febrile neutropenia, thrombocytopenia, fatigue, and hyperglycemia were increased with cixutumumab.Conclusions: The addition of cixutumumab to CPB increased toxicity without improving efficacy and is not recommended for further development in NSCLC. Both treatment groups had longer OS than historical controls which may be attributed to several factors, and emphasizes the value of a comparator arm in phase II trials.ClinicalTrials.gov Identifier: NCT00955305

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