EORTC 1410-BTG/AbbVie M14-483
The median survival for patients diagnosed with glioblastoma, a form of brain cancer, is just 9 to 15 months. Even with aggressive treatment, patients with glioblastomas inevitably relapse after the standard treatment which includes surgery, radiotherapy, and temozolomide chemotherapy. There is no cure for this disease which is considered to be the most aggressive primary brain tumor in adults.
Previous attempts to improve treatment for patients with recurrent glioblastoma focused on the use of drugs that inhibited the epidermal growth factor receptor, a receptor that is found in disproportionately high concentrations and sometimes is mutated in glioblastomas. Unfortunately, the drugs used, monoclonal antibodies or tyrosine kinase inhibitors, have not proved effective so far in clinical studies.
Prof. Martin van den Bent of the Erasmus MC Cancer Institute in Rotterdam and Coordinator of this study points out, “Targeting the epidermal growth factor receptor remains a logical approach, and another way to do this would be to use the activated epidermal growth factor receptor to target the tumor cell with highly toxic agents. Activated epidermal growth factor receptors are found in more than half of all glioblastomas. These receptors will be targeted by ABT 414, an antibody-drug conjugate that binds specifically to a unique epitope of the activated human epidermal growth factor receptor and carries a very potent cytostatic. This approach has been very successful in other solid cancers.”
EORTC 1410-BTG/AbbVie M14-483 will assess whether ABT 414 alone or in combination with temozolomide improves overall survival, progression-free survival, tumor response, quality of life, neurological deterioration-free survival, and steroid use compared to standard treatment with lomustine alone or temozolomide re-challenge in patients with centrally confirmed recurrent EGFR-amplified glioblastoma. The primary endpoint is overall survival at final analysis and progression-free survival according to Response Assessment in Neuro-Oncology (RANO) criteria and by an Independent Review Committee at the interim analysis.
EORTC trial 1410-BTG plans to accrue 240 patients and is being conducted at 35 EORTC network sites located in eight countries, Austria, Belgium, France, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom, and by AbbVie affiliates located in Australia, Canada, Czech Republic, Finland, Hungary, Ireland, Korea, Mexico, Poland, Puerto Rico, Singapore, Spain, Taiwan, and the United States. EORTC holds the database and is responsible for all statistical analyses. This trial is funded by AbbVie.
John Bean, PhD
EORTC, Medical Science Writer