Use of Monoclonal Anti-EGFR Antibody in the Radioimmunotherapy of Malignant Gliomas in the Context of EGFR Expression in Grade III and IV Tumors

Abstract

We investigated the putative benefits of simultaneous teleradiotherapy and anti-epidermal growth factor receptor (EGFR) 125I monoclonal antibody (MAb) 425 radioimmunotherapy, when applied after neurosurgery in high-grade gliomas, over teleradiotherapy alone. In comparison to previous studies which have reported good results with this type of radioimmunotherapy, we advanced the adjuvant radioimmunotherapy step, that is, gave it during, not after, teleradiotherapy. The randomized prospective study examined two groups: simultaneous postoperative teleradiotherapy and radioimmunotherapy (TRT + RIT; eight patients) versus teleradiotherapy alone (TRT; 10 patients). Patients who after primary operation of grade III (6 cases) or IV glioma (12 cases), showed no or less than 2 mL of remnant tumor on post-operative magnetic resonance (MR) study and were not treated postoperatively by chemotherapy were enrolled and randomized. Anti-EGFR 125IMAb 425 RIT was started during week 4 of radiotherapy, not later than 8 weeks after neurosurgery, and was repeated three times at 1-week intervals. Total activity given was 5026 + 739 MBq/patient. The tolerance of TRT was good. No immediate side effects of concomitant anti-EGRF 125I RIT were observed. Observation showed a median total survival (as evaluated from the primary neurosurgical treatment) of 14 months (range 3.5-28 months). There was no improvement in disease-free or total survival in the group of patients treated by TRT + RIT after neurosurgery. In addition, an immunohistochemical analysis of EGFR expression in gliomas was performed in a group of 100 cases and was distinctly positive in 50% grade IV gliomas and 68% grade III gliomas. We conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR 125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of high-grade gliomas after neurosurgery. We also recommend individual confirmation of EGFR expression in further anti-EGFR radioimmunotherapy trials.

The EGFRvIII variant in glioblastoma multiforme

“…21,92 However, a randomized trial of adjuvant radioimmunotherapy with iodine-125 labeled mAb 425 showed no additional benefit compared to surgery and radiotherapy alone. 93 Only a few trials have reported on EGFRvIII specific therapy in glioma patients (Table 1). Scott et al recently reported on a Phase I trial of a single dose of mAb 806 in patients with several tumour types including one patient with glioma.…”

Molecularly Targeted Therapies for Malignant Gliomas

“…A median OS of 14 months for both treatment groups was observed, with no improvement in disease-free survival or OS in either treatment group after neurosurgery (48). Therefore, radiotherapy and radioimmunotherapy with anti-EGFR 125 I-MAb 425 was not beneficial compared with radiotherapy alone for the adjuvant treatment of high-grade gliomas following neurosurgery (48). Therefore, compared with the standard Stupp regimen (OS range for GBM was 13.2 to 16.8 months) (18), 125 I-MAb 425 greatly increased the OS range.…”

“…The actuarial OS range for GBM and AA patients was 4 to 150 and 4 to 270 months, respectively (47). A similar study investigated the putative benefits of teleradiotherapy and 125 I-MAb 425 radioimmunotherapy administered after neurosurgery in high-grade gliomas compared with teleradiotherapy alone (48). A median OS of 14 months for both treatment groups was observed, with no improvement in disease-free survival or OS in either treatment group after neurosurgery (48).…”

“…A similar study investigated the putative benefits of teleradiotherapy and 125 I-MAb 425 radioimmunotherapy administered after neurosurgery in high-grade gliomas compared with teleradiotherapy alone (48). A median OS of 14 months for both treatment groups was observed, with no improvement in disease-free survival or OS in either treatment group after neurosurgery (48). Therefore, radiotherapy and radioimmunotherapy with anti-EGFR 125 I-MAb 425 was not beneficial compared with radiotherapy alone for the adjuvant treatment of high-grade gliomas following neurosurgery (48).…”

“…However, interpretation of data from trials, such as those described above, is challenging because of methodological problems, mainly consisting of the small sample sizes enrolled and the open-label study design (48)(49)(50)52).…”