A multicenter stratified phase II study of cetuximab for the treatment of patients with recurrent high-grade glioma

Abstract

2017 Background: An increased copy number and mutation of the epidermal growth factor receptor (EGFR) gene are frequently found in high-grade gliomas (HGG). We investigated the activity of the EGFR-blocking monoclonal antibody cetuximab for the treatment of patients (pts) with recurrent HGG following surgery, radiotherapy, and chemotherapy. Methods: Eligible adult pts were treated with cetuximab (400 mg/m2 2 h IV on d1 and weekly 250 mg/m2 1h IV thereafter). Pts were stratified in 2 treatment arms according to the amplification status of the EGFR gene of their HGG (determined by fluorescence in situ hybridization on archival tumor material). Results: Between May 2005 and December 2007 a total of 55 pts with performance status 0–2 initiated treatment with cetuximab (28 pts with and 27 pts without an increased EGFR copy number, 17F/38M, median age 53 years [range 32–73]). Cetuximab was generally well tolerated. During a total of 689 treatment weeks the most frequent treatment-related adverse events were: skin toxicity (grade 2, n=12; grade 3, n=4), thrombocytopenia (grade 2, n=1; grade 3, n=2), confusion/diminished consciousness (grade 3, n=4 pt), lymphopenia (grade 4, n=1), infusion related allergic reaction (grade 2, n=1), intratumoral hemorrhage (grade 2, n=1), diarrhea (grade 2, n=1), and fatigue (grade 2, n=3). A dose reduction of cetuximab (to 200 mg/m² weekly) was necessary in 2 pts. After a median follow-up of 15 months, 11 pts are alive (5 are still receiving cetuximab) and 44 pts have died. The disease control rate was 35% (3 pts (5.6%) had a PR and 16 pts (29.6%) had SD) and 35 pts (64.8%) had PD. The median PFS was 1.9 months, median OS was 5.0 months. The 6-month PFS and OS rates were 10% and 40%, respectively. Whereas PFS was less than 5 months in the majority (n=49) of pts, a subgroup of 5 pts (9.2%) have a PFS on cetuximab of more than 9 months (range 9.5 to >16.5). No significant correlation was found between response, survival and EGFR copy number. Conclusions: Cetuximab as a single agent was safe and well tolerated in this population of pretreated patients with recurrent high-grade glioma. Durable disease control was observed in a small subgroup of patients. Mature results of this study will be available for presentation at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Merck, sanofi-aventis, Schering-Plough, Wyeth Merck