Abstract 4553
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.
Resources from the same session
3158 - Tobacco Retail Access and Tobacco Cessation Among Head and Neck Cancer (HNC) Survivors
Presenter: Lawson Eng
Session: Poster Display session 1
Resources:
Abstract
5511 - ASSERT: A Prospective, Observational Study Measuring Sodium Improvement and Outcomes in Patients Treated for Moderate to Severe Hyponatremia Secondary to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in Italy (Lung Cancer Cohort)
Presenter: Rossana Berardi
Session: Poster Display session 1
Resources:
Abstract
3821 - Efficacy and safety of controlled ovarian stimulation with or without letrozole co-administration for fertility preservation: A systematic review and meta-analysis.
Presenter: Benedetta Bonardi
Session: Poster Display session 1
Resources:
Abstract
2168 - Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy
Presenter: Tineke Vandenbroucke
Session: Poster Display session 1
Resources:
Abstract
5855 - Update of the registry of young women with cancer by the International Network of Cancer, Infertility and Pregnancy
Presenter: Charlotte Maggen
Session: Poster Display session 1
Resources:
Abstract
5156 - Erectile dysfunction in patients with metastatic renal cell carcinoma
Presenter: Ilya Tsimafeyeu
Session: Poster Display session 1
Resources:
Abstract
4992 - Exercise level, interest and preferences in cancer patients.
Presenter: Alice Avancini
Session: Poster Display session 1
Resources:
Abstract
3427 - Filling the Gaps in Informed Consent for Advanced Cancer Patients considering Phase 1 Oncology Trials - an in-depth Qualitative Study of Key Stakeholders at a large United Kingdom Phase 1 unit
Presenter: Abhijit Pal
Session: Poster Display session 1
Resources:
Abstract
3537 - Breast Cancer Patients’ Quality of Life: Real World Data
Presenter: Thanos Kosmidis
Session: Poster Display session 1
Resources:
Abstract
4761 - High-sensitivity troponin as a cardiotoxicity biomarker in breast cancer treatment
Presenter: Joana Simões
Session: Poster Display session 1
Resources:
Abstract