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
4546 - Efficacy and toxicity of weekly carboplatin and paclitaxel as induction or palliative treatment in advanced esophageal cancer patients
Presenter: Femke de Man
Session: Poster Display session 2
Resources:
Abstract
5908 - Perioperative chemotherapy with Docetaxel, Oxaliplatin, Fluorouracil and Leucovorin (FLOT) versus Epirubicin, Platinum and Capecitabine or Flourouracil (EOX/ECF) in Resectable Gastric or Gastroesophageal Junction Adenocarcinoma- Safety and response data from India.
Presenter: Tanuj Chawla
Session: Poster Display session 2
Resources:
Abstract
937 - Phase II Study of Preoperative Radiotherapy Combined with S-1 plus Cisplatin in Clinically Resectable Type 4 or Large Type 3 Gastric Cancer: OGSG1205
Presenter: Shunji Endo
Session: Poster Display session 2
Resources:
Abstract
1119 - Observational Study of the Peritoneal Washing Cytology Positive Gastric Cancer without Gross Peritoneal Metastasis Underwent Radical D2 Gastrectomy.
Presenter: Jun Eul Hwang
Session: Poster Display session 2
Resources:
Abstract
3744 - Primary results of multicenter phase II study of neoadjuvant chemotherapy with S-1 and oxaliplatin for locally advanced gastric cancer (Neo G-SOX PII)
Presenter: Akira Miki
Session: Poster Display session 2
Resources:
Abstract
5091 - Multicenter Phase I/II Feasibility Study of Adjuvant Treatment with S-1 in Patients after R0-Resection of Adenocarcinoma of the Stomach and Esophagogastric Junction (GMBH-STO-0114)
Presenter: Kathrin Heinrich
Session: Poster Display session 2
Resources:
Abstract
2891 - A phase I study of Docetaxel/Oxaliplatin/S-1 (DOS) combination neoadjuvant chemotherapy for patients with locally advanced adenocarcinoma of the esophagogastric junction
Presenter: Kei Hosoda
Session: Poster Display session 2
Resources:
Abstract
2994 - Apatinib combined with docetaxel in second-line treatment of advanced gastric cancer: a prospective clinical study (Data updated)
Presenter: Mudan Yang
Session: Poster Display session 2
Resources:
Abstract
3000 - A multicenter phase II study of TAS-114 in combination with S-1 in patients with pre-treated advanced gastric cancer (EPOC1604)
Presenter: Daisuke Takahari
Session: Poster Display session 2
Resources:
Abstract
4653 - Impact of Pembrolizumab (pembro) Versus Paclitaxel on Health-Related Quality of Life (HRQoL) in Patients With Advanced Gastric or Gastroesophageal Junction (GEJ) Cancer That Has Progressed After First-Line Chemotherapy (KEYNOTE-061)
Presenter: Eric Van Cutsem
Session: Poster Display session 2
Resources:
Abstract