Efficacy of racotumomab or nimotuzumab vs docetaxel as second-line therapy for advanced non-small cell lung cancer patients

Background: Racotumomab-alum is an anti-idiotypic vaccine that induces immunological response against N-glycolilated gangliosides in NSCLC patients. Nimotuzumab is a humanized anti-EGFR monoclonal antibody that has shown activity in NSCLC patients. The aim of this study is to evaluate safety and efficacy of racotumomab-alum or nimotuzumab versus docetaxel as second line or switch maintenance therapy for advanced NSCLC. Methods: This phase III, multicenter, open label, randomized trial is designed to enroll 743 stage IIIB-IV NSCLC patients, after first line therapy, with PS 0-2, with written informed consent. The primary endpoint is Overall Survival (OS). Patients are been randomized (2:2:1) to 3 arms: racotumomab-alum, nimotuzumab or docetaxel, and stratified according to response to first line (progressor or non-progressor patients). Racotumomab-alum treatment consists in 5 bi-weekly intradermal doses and re-immunizations every 4 weeks. Nimotuzumab arm receives 6 weekly infusions followed by bi-weekly doses. Docetaxel is used at 75 mg/m2 for 6 cycles, if there is no evidence of progressive disease after 3 cycles. As second-line therapy, both experimental drugs will be classified as non-inferior (NI) to docetaxel, if 1- year OS rate is 23.1 % and HR C/T=0.76, [d0 (0,28), d0= - ln HR(C/T)] using a 10% NI margin. Here we report the interim analysis in 255 progressor patients. Results: 106 patients in racotumomab, 97 in nimotuzumab and 54 in docetaxel arm with at least 1 year follow up were analyzed (ITT). The median OS and 1-year survival rate were 4.67 months (CI: 4.0-5.3) and 14.5 % with nimotuzumab, 4.83 months (CI: 3.7-5.9) and 23.5 % with racotumomab-alum and 5.85 months (CI: 3.9-7.7) and 20.2 % with docetaxel, respectively. Most frequent treatment-related adverse events were induration (10.7%), local erythema in injection site (8.8%) and arthralgia (8.2%) with racotumomab-alum; myalgia (12.1%), fever (7.9%) and nausea (7.0%) with nimotuzumab, and nausea (16.5%), asthenia (13.2%) and vomiting (12.1%) after docetaxel. Conclusions: These data do not confirm the non-inferiority of racotumomab-alum or nimotuzumab versus docetaxel as second-line therapy. Both experimental treatments were safely administered at primary level of health assistance. Clinical trial identification: RPCEC0000017. Legal entity responsible for the study: Center of Molecular Immunology. Funding: Center for Molecular Immunology. Disclosure: M. Hernandez, C. Viada, T. Crombet: Employed: Center of Molecular Immunology. All other authors have declared no conflicts of interest.