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. 2018 Jan-Mar;13(1):46-52.
doi: 10.4103/ajns.AJNS_95_17.

Significant Effect of Anti-tyrosine Kinase Inhibitor (Gefitinib) on Overall Survival of the Glioblastoma Multiforme Patients in the Backdrop of Mutational Status of Epidermal Growth Factor Receptor and PTEN Genes

Sajad Hussain Arif  1 , Arshad Ahmad Pandith  2 , Rehana Tabasum  2 , Altaf Umar Ramzan  1 , Sarabjeet Singh  1 , Mushtaq Ahmad Siddiqi  3 , Abdul Rashid Bhat  1
Affiliations

Significant Effect of Anti-tyrosine Kinase Inhibitor (Gefitinib) on Overall Survival of the Glioblastoma Multiforme Patients in the Backdrop of Mutational Status of Epidermal Growth Factor Receptor and PTEN Genes

Sajad Hussain Arif et al. Asian J Neurosurg. 2018 Jan-Mar.

Abstract

Introduction: We aimed to assess the effect of anti-tyrosine kinase inhibitors (TKIs) (gefitinib) in overall survival (OS) of the glioblastoma multiforme (GBM) patients in the backdrop of mutational status of epidermal growth factor receptor (EGFR) and PTEN genes.

Materials and methods: All the patients subjected to resection or biopsies were put on gefitinib, and radiotherapy was delivered as per the hospital protocol. EGFR and PTEN mutational spectrum was performed by single-strand conformation polymorphism followed by DNA sequencing.

Results: In total, 50% GBM tumors had mutation either in EGFR or PTEN. Median progression-free survival (PFS) and OS observed in patients with EGFR +ve/PTEN -ve were significantly favorable (P < 0.05) which aggregated to 9(7, 11) months and 20 (16, 24) months, respectively, than 6 (4, 8) months and 13 (7, 19) months in patients with PTEN +ve/EGFR -ve. Patients positive for both EGFR/PTEN had lower disease-free survival and OS of 6 and 9 months as compared to 6 (5, 7) and 14 (12, 24) months for those negative for both EGFR/PTEN.

Conclusions: We conclude that EGFR gene alterations with wild-type PTEN are associated with significantly better PFS and OS in patients treated with anti-TKIs (gefitinib). Combined EGFR and PTEN gene mutation is associated with significantly poor response to gefitinib in terms of median OS.

Keywords: Anti-tyrosine kinases; DNA sequencing; PTEN; epidermal growth factor receptor; gefitinib; glioblastoma multiforme; mutations.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
(a) Kaplan–Meier curve of overall survival and progression-free survival as a function age. (b) Kaplan–Meier curve of overall survival and progression-free survival as a function gender. (c) Kaplan–Meir curve to evaluate effect of mutational spectrum of epidermal growth factor receptor/PTEN as a component of overall survival. (d) Kaplan–Meir curve to evaluate effect of mutational spectrum of epidermal growth factor receptor/PTEN in relation to progression-free survival
See this image and copyright information in PMC

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