The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to researchers, patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC) treated with first-line osimertinib therapy had a lower disease control rate (DCR) and worse overall survival (OS) when their disease was also characterized by a TP53 mutation. These findings were presented at the European Society for Medical Oncology (ESMO) Congress 2019 held in Barcelona, Spain.  

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is approved by both the US Food and Drug Administration (FDA) and the European Commission for the first-line treatment of patients with advanced NSCLC characterized by an activating EGFR mutation, as well as for those with advanced EGFR T790M-mutant NSCLC. 

Uncovering biomarkers of response and resistance to osimertinib is a key component for the optimization of first-line therapy in individual patients with EGFR-mutant advanced NSCLC. 

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The objective of this study was to determine whether benefit from first-line osimertinib was affected by the presence of 1 or more TP53 mutations in advanced EGFR-positive NSCLC that had metastasized to the brain.  

Of the 100 patients with EGFR-mutant disease included in this study, all had disease characterized by brain metastases and were undergoing treatment with first-line osimertinib. In this cohort, TP53 mutations were observed in 48% of patients. Specifically, TP53 mutations were localized in exon 5, exon 6, exon 7, and exon 8 in 22.92%, 14.58%, 25%, and 37.5% of these patients, respectively. 

Notably, brain metastases were more extensive in patients with TP53-mutated disease compared with those with disease not characterized by a TP53 mutation (P <.05)

Furthermore, comparisons of the clinical outcomes of patients with TP53-mutant versus non–TP53-mutant disease treated with osimertinib showed a significantly lower DCR (29.17% vs 94.23%), as well as significantly shorter median progression-free survival (PFS) (4.8 months vs 10 months, P <.001) and median OS (10.98 months vs 25.45 months, P <.001) in those with disease characterized by a TP53 mutation. 

When patient outcomes were analyzed with respect to the genomic locations of the TP53 mutations, all patients with TP53 exon 8 mutations demonstrated primary resistance to first-line osimertinib. In addition, in analyses incorporating all TP53 mutant subtypes, a TP53 mutation in exon 8 was shown to be an independent biomarker of poor prognosis (P <.001).

In their concluding comments, the researchers noted that “a TP53 mutation might be used as a predictor for [benefit from] osimertinib therapy and a prognostic factor for EGFR-mutated NSCLC patients with brain metastasis.”

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.


  1. Chen L, et al. Association between TP53 mutations and efficacy of osimertinib for brain metastasis from EGFR-mutant lung cancer. Presented at: European Society for Medical Oncology (ESMO) Congress 2019; September 27-October 1, 2019: Barcelona, Spain. Abstract 405P.