Efficacy of erlotinib in patients with relapsed gliobastoma multiforme who expressed EGFRVIII and PTEN determined by immunohistochemistry

Abstract

Epidermal growth factor receptor gene (EGFR) alteration is a common feature in most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII) and expression of PTEN. We have performed a prospective trial in order to confirm the efficacy of erlotinib treatment in patients with relapsed GBM who expressed EGFRvIII and PTEN. All patients included in the trial were required to be PTEN (+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry. This new phase II trial enrolled 40 patients and was design to be stopped in case of fewer than two responses in the first 13 patients. Patient eligibility included histopathology criteria, radiological progression, more than 18 years old, Karnofsky performed status, KPS > 50, and adequate bone marrow and organ function. There was no limit to the number of prior treatments for relapses. No enzyme-inducing antiepileptic drugs were allowed. The primary endpoints were response and progression-free survival at 6 months (PFS6). Thirteen patients (6 men, 7 women) with recurrent GBM received erlotinib 150 mg/day. Median age was 53 years, median KPS was 80, and median prior treatments for relapses were 2. There was one partial response and three stable diseases (one at 18 months). PFS at 6 months was 20 %. Dose reduction for toxicity was not needed in any patient. Dermatitis was the main treatment-related toxicity, grade 1 in 8 patients and grade 2 in 5 patients. No grade 3 toxicity was observed. Median survival was 7 months (95 % IC 1.41–4.7). As conclusion, monotherapy with erlotinib in GBM relapses patients with high protein expression for PTEN (+++), EGFR (+++), and EGFRvlII (+++) showed low toxicity but minimal efficacy and the trial stopped.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-013-1316-y) contains supplementary material, which is available to authorized users.

Connexin 43 C‐terminus directly inhibits the hyperphosphorylation of Akt/ERK through protein–protein interactions in glioblastoma

“…Our findings are consistent with those of other studies, indicating that GBM patients not selected for any biological characteristic show modest response to EGFR inhibitors . The association of EGFR amplification with GBM tumors led to early optimism that EGFR inhibition would be beneficial.…”

Nonsurgical Treatment of Recurrent Glioblastoma

“…In a series of 41 patients, Haas-Kogan et al reported observing 8 responses in individuals who expressed high levels of egfr and low levels of Akt. A recent prospective study of erlotinib 55 did not reproduce the latter findings. Conducted in patients with recurrent gbm and with co-expression of egfrviii and pten determined by immunohistochemistry, that study reported an os of 7 months and a pfs of 3 months.…”

Biomarkers in Glioblastoma multiforme. Evidences from a literature review

“…Studies reporting the prognostic or predictive value of EGFRvIII are listed in Table 1 [8,15,16,[21][22][23][24][25][26][27][28][29][30][31][32][33][34]. We found 17 studies considering 1656 GBM patients overall.…”