Abstract 389P
Background
EGFR is a key oncogenic driver mutation in brain cancers, but unlike that often occur in exon 18-21 of EGFR in lung tumors, the main mutations in brain cancer are EGFRVIII and EGFR amplification. Previous studies have shown that the first/second EGFR-TKIs have no significant therapeutic effect in brain cancers most likely due to a low degree of penetration across the blood-brain barrier (BBB) and different EGFR mutation features in brain cancer. Osimertinib, as the latest generation EGFR-TKI, has greater permeability of BBB and can target a broader EGFR mutations spectrum. Little is known about the potential benefits of osimertinib in brain cancers. Herein, we retrospectively analyzed the mutation spectrum of EGFR in primary brain tumors and assessed the proportion of patients who might benefit from osimertinib.
Methods
A total of 3,870 patients of primary brain tumors between 2017 and 2019 were included in this study. Tumor tissue or ctDNA of these patients were subjected to EGFR-included DNA panel sequencing. EGFR mutation spectrum and sensitizing EGFR mutations of osimertinib were analyzed.
Results
11.01% (426/3870) of the patients had SNVs/Indels in EGFR. Among them, 77.46% (330/426) had only one EGFR mutations, others were with multiple EGFR mutations. In a total of 566 different EGFR SNVs/Indels, 91.53% (518/566) were missense variants and 6.00% were Indels. 74.9% (424/566) of these mutations occurred in exon 7 and 15, only 22.26% (126/566) mutated in exon 18-21 and no L858R or 19del were found in this big cohort, which differ from that of lung cancer and may be the reasons for the ineffectiveness of first/second EGFR-TKI in brain tumors. Take osimertinib-sensitizing EGFR mutations into consideration, 0.98% (38/3870) of the patients harbored osimertinib-sensitive EGFR mutations in our data, and 65.79% (25/38) of these mutations occurred in G719 (G719A-7pts, G719C-2pts, G719D-10pts, G719S-6pts).
Conclusions
To our knowledge, this is the first and biggest study to investigate the potential benefit of osimertinib in primary brain tumors. In a 3,870 patients’ cohort, only 0.98% of the patients contain osimertinib-sensitive mutations and mainly in G719 position. This small group of patients may benefit from Osimertinib.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.