Abstract 5123
Background
Hotspot mutations (HSM) in TP53 (R175, Y220, G245; R248, R273) have been recognized as potential immunoreactive neoantigens able to achieve intratumoral T cell responses in advanced ovarian cancer, particularly in high-grade serous ovarian cancer (HGSOC). The purpose of this study was to assess if HSM, Non-HSM (missense non-HSM) and Other (INDELs, stop gained, splice site) somatic mutations in TP53, confer differential survival outcomes. Presence of circulating p53-autoantibodies (p53-AAbs) was also tested and correlated with TP53 mutation spectra.
Methods
A series of 83 patients (71 HGSOC) with advanced (III-IV stage, G2-3) ovarian cancer, treated with primary debulking surgery and platinum-based therapy, were retrospectively enrolled. Characterization of TP53 mutations in chemo-naïve tumours was performed with a targeted next-generation sequencing approach. An ELISA kit was used to detect p53-AAbs. Platinum-free interval (PFI), progression-free survival (PFS) and Overall survival (OS) were compared using Kaplan-Meier, Log-rank test and Cox proportional hazard models (adjusted for age, stage, serous subtype, residual tumour).
Results
Somatic mutations in TP53 were found in 74.7% of patients; among them, 71% was -p53-AAbs and 29% was +p53-AAbs. The repertoire of TP53 mutations was significantly different according to p53-AAbs (p = 0.005), with prevalence of Other mutations (50%) in patients -p53-AAbs. In multivariate analysis (WT as the ref. category), patients with: i) Non-HSM mutations had reduced PFI (p = 0.026), PFS (p = 0.014) and OS (p = 0.048); ii) Other mutations had reduced PFI (p = 0.002) and PFS (p = 0.007), but not OS (p = 0.062); iii) HSM mutations were not associated with PFI (p = 0.605), PFS (p = 0.681) and OS (p = 0.437).
Conclusions
Molecular profile of chemo-naïve tumours in advanced ovarian cancer showed different outcomes coupled to specific TP53 signatures. A more aggressive mutational profile in TP53 was observed in patients without p53-AAbs. Non-synonymous mutated neoantigens arised from tumour clones, appear to be critical to identify patients best suited to immunotherapy. Further investigations in the tumour microenvironment are needed to confirm these preliminary findings.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Giorgio Giorda.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
733 - Clinical experience: ramucirumab with FOLFIRI/XELIRI as a second line for patients with metastatic gastric cancer
Presenter: Tatiana Titova
Session: Poster Display session 2
Resources:
Abstract
2186 - Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer
Presenter: Ningning Li
Session: Poster Display session 2
Resources:
Abstract
3172 - Apatinib in combination with docetaxol and S1 chemotherapy in the first line treatment of metastatic gastric cancer
Presenter: Ling Xia
Session: Poster Display session 2
Resources:
Abstract
3982 - Parameters of local cellular immunity in metastatic gastric cancer
Presenter: Aleksandr Sagakyants
Session: Poster Display session 2
Resources:
Abstract
5102 - Germline pathogenic mutations in Chinese patients with gastric cancer identified by next-generation sequencing (NGS)
Presenter: Xiaotian Zhang
Session: Poster Display session 2
Resources:
Abstract
5012 - Inhibition of the PI3K pathway in HER2-positive gastric cancer
Presenter: Sinead Toomey
Session: Poster Display session 2
Resources:
Abstract
4803 - Investigation on gastric cancer susceptibility genes in Chinese early-onset diffuse gastric cancer
Presenter: Yi Feng
Session: Poster Display session 2
Resources:
Abstract
4778 - A correlation analysis between survival rate and the characteristic gene of gastric cancer based on bioinformatics analysis
Presenter: Yi-wen Zhang
Session: Poster Display session 2
Resources:
Abstract
4805 - Phase I study of apatinib combined with POF (paclitaxel plus FOLFOX) in patients (pts) with treatment-naïve advanced gastric cancer (TNAGC)
Presenter: Rongbo LIN
Session: Poster Display session 2
Resources:
Abstract
3248 - Second-line palliative systemic treatment for synchronous metastatic esophagogastric cancer: a population-based study
Presenter: Willemieke Dijksterhuis
Session: Poster Display session 2
Resources:
Abstract