|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.
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.
- 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.