4553 - Association between TP53 mutations and efficacy of Osimertinib for brain metastasis from EGFR-mutant lung cancer

Background

Osimertinib was approved as a standard therapy for EGFR-mutant lung cancer with brain metastasis. It has been demonstrated that TP53 mutations was responsible for Gefitinib resistance in a preclinical study. This study was to analyze the impact of TP53 mutations on response to first-line Osimertinib in EGFR-mutant patients with brain metastasis from non-small cell lung cancer (NSCLC).

Methods

100 EGFR-mutated NSCLC patients with brain metastasis receiving first-line Osimertinib were analyzed. TP53 mutations were evaluated in all patients in relation to disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

Results

TP53 mutations were observed in 48 (48%), 11 (22.92%), 7 (14.58%), 12 (25%) and 18 (37.5%) patients in exon 5, 6, 7, and 8, respectively. TP53 mutations were significantly associated with increasing brain-metastatic sites (P < 0.05). DCR was 29.17% in TP53-mutated patients compared to 94.23% in patients with TP53-wild type (P < 0.05). All patients with TP53 exon 8 mutations had primary resistance to Osimertinib. Compared with others, significantly shorter median PFS and OS were observed both in total TP53-mutated patients (mPFS 4.8 vs 10 months, P < 0.001; mOS 10.98 vs 25.45 months, P < 0.001) and patients with TP53 exon 8 mutations ((mPFS 4 vs 9 months, P < 0.001; mOS 8.25 vs 19.98 months, P < 0.001)), compared with others. TP53 exon 8 mutation was an independent prognostic factor adjusting for other subtypes of TP53 mutation (P < 0.001).

Conclusions

TP53 mutations, especially exon 8 mutations, reduced the efficacy of Osimertinib and worsen prognosis in EGFR-mutated NSCLC patients with brain metastasis. TP53 mutation might be used as a predictor for Osimertinib therapy and a prognostic factor for EGFR-mutated NSCLC patients with brain metastasis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Yanqiu Zhao.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.