Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial

Abstract

Background : Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. Methods : Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. Results : A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. Conclusions : Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.

Multidisciplinary Therapy Managed Recurrent Glioblastoma in a BRAF-V600E Mutant Pregnant Female: A Case Report and Review of the Literature

“…The nimotuzamab was administered to reduce the edema of the surrounding area of the postoperative tumor cavity, and also to elongate the period of stable disease. As previously reported, nimotuzumab in addition to standard treatment is well-tolerable and has increased survival in GBM patients with EGFR positive ( 43 ), we underwent nimotuzamab with temozolomide and RT contemporarily after the second craniotomy without the gene sequencing result coming out, even though the genetic test claimed EGFR negative in this patient afterwards.…”

Molecular and Cellular Complexity of Glioma. Focus on Tumour Microenvironment and the Use of Molecular and Imaging Biomarkers to Overcome Treatment Resistance

“…The median OS and PFS were 24.5 and 11.9 months, respectively. These data may be of interest for a phase III clinical randomized controlled trial [136].…”

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

“…Cetuximab, panitumumab and nimotuzumab are FDA-approved anti-EGFR antibodies that bind to the L2 domain, preventing ligand binding and/or dimerization of EGFR [ 119 ]. While both cetuximab and panitumumab failed to demonstrate efficacy for recurrent GB, preclinical and multiple clinical trials with nimotuzumab in high-grade glioma patients gave promising results [ 102 , 103 , 107 , 108 ].…”