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
4331 - STING Agonist, ADU-S100, Yields Potent Antitumor Activity and Therapeutically Favorable Immune Profile in an Esophageal Adenocarcinoma Model
Presenter: Ali Zaidi
Session: Poster Display session 2
Resources:
Abstract
1770 - Increased assessment of HER2 in metastatic gastroesophageal cancer patients: a nationwide population-based cohort study
Presenter: Willemieke Dijksterhuis
Session: Poster Display session 2
Resources:
Abstract
3755 - A new docetaxel (DOC)-based triplet regimen does not improve the outcome of metastatic (M) or locally advanced (LA) gastric cancer (GC) as compared with an epirubicin (EPI) standard triplet regimen: a GISCAD trial.
Presenter: Roberto Labianca
Session: Poster Display session 2
Resources:
Abstract
2439 - The analysis of T cell subsets and clinical efficacy of immune checkpoint blockades in patients with advanced gastric cancer using multiplex immunohistochemistry
Presenter: Tae-yong Kim
Session: Poster Display session 2
Resources:
Abstract
2211 - First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma.
Presenter: Yelena Janjigian
Session: Poster Display session 2
Resources:
Abstract
3046 - Monitoring patient-specific mutation in ctDNA and CTC for tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric cancer (NCT03425058)
Presenter: Tao Fu
Session: Poster Display session 2
Resources:
Abstract
4628 - Gastric cancer screening in BRCA 2 gene mutation carriers: should it be recommended?
Presenter: Inês Oliveira
Session: Poster Display session 2
Resources:
Abstract
2127 - Interim analysis of an observational/translational study for nivolumab treatment in advanced gastric cancer: JACCRO GC-08 (DELIVER trial)
Presenter: Yu Sunakawa
Session: Poster Display session 2
Resources:
Abstract
2264 - Prediction of S-1 adjuvant chemotherapy efficacy in Stage II/III gastric cancer treatment based on comprehensive gene expression analysis
Presenter: Masanori Terashima
Session: Poster Display session 2
Resources:
Abstract
2444 - Assessing the clinical utility of circulating tumour DNA through longitudinal liquid biopsy sampling in Oesophageal adenocarcinoma
Presenter: Emma Ococks
Session: Poster Display session 2
Resources:
Abstract