Radiotherapy plus the anti-EGFR mAb nimotuzumab or placebo for the treatment of high-grade glioma patients.

Abstract

2515 Background: Despite remarkable advances in multimodal therapy, high grade glioma (HGG) patients still face a poor prognosis. EGFR is well validated as a primary contributor of HGG initiation and progression. Nimotuzumab is a humanized monoclonal antibody (mAbs) that recognizes the EGFR extracellular domain. While it has similar preclinical and clinical activity when compared to other anti-EGFR mAbs, it does not induce skin toxicity or hypomagnesemia. Methods: A randomized, double blind, multicentric clinical trial was conducted in 70 anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) patients that received radiotherapy (RT) plus nimotuzumab or placebo. Patients received 6 weekly doses of nimotuzumab or placebo together with radiotherapy. Treatment was maintained every 3 weeks, until completing 1 year of treatment. GBM patients did not receive temozolomide since the drug cannot be sold to Cuba. The objectives of this study were to assess the overall survival, progression free survival (PFS), response rate, immunogenicity and safety in both treatment groups. Results: Seventy patients were included in the study: 41 AA and 29 GBM. The median cumulative dose was 3600 mg of nimotuzumab and the median antibody number of doses was 16. The combination of nimotuzumab and radiotherapy was very safe. The most prevalent related adverse events included grade 1-2 nausea, fever, tremors and anorexia. There was no increasing toxicity with repeated drug exposure. No anti-idyotipic response was detected. The mean and median survival time for subjects treated with nimotuzumab and RT was 31.06 and 17.76 months while the mean and median survival time for controls was 21.07 and 12.63 months, respectively. For the evaluable patients of the AA stratum, the median survival time was 44.56 months (active drug) vs. 14.6 months (control). For the evaluable patients in the GBM cohort, the median survival time was 16.06 months (nimotuzumab arm) vs. 8.36 months (placebo arm). Median PFS was 18.23 vs. 6.25 months. Conclusions: In this randomized trial, nimotuzumab continues showing an excellent safety profile and positive efficacy results in patients with high grade glioma in combination with irradiation.