Abstract 4288
Background
Genomic profiling of blood-derived circulating tumour DNA (ctDNA) which is considered as a minimally invasive biopsy, has several potential applications in the management of ovarian cancer, including selection of targeted therapy, drug resistance prediction and the evaluation of treatment response. Therefore, we conducted this study to characterize genomic alterations (GA) in ctDNA from patients with ovarian cancer and compare GA detected in ctDNA with those detected in tissue databases.
Methods
Hybrid capture-based next generation sequencing (NGS) genomic profiling of 150 genes was performed on ctNDA from 76 patients with ovarian cancer in a CAP-accredited laboratory. The GA detected in ctDNA were compared with the 3D Med tissue database tested by NGS (N = 260) and TCGA database tested by whole-exon sequencing (N = 587). The fraction of ctDNA was estimated using the maximum somatic allele frequency (MSAF). GAs including single nucleotide variation (SNV), insertions/deletions, copy number variations, gene rearrangement and fusions were assessed. Germline alterations were excluded.
Results
89.5% (68/76) of patients (median age 57) detected ≥1 GA in ctDNA. Frequently altered genes detected in ctDNA for SNV were TP53 (52.6%), AR (11.8%), KRAS (9.2%), NOTCH2 (6.6%) and PIK3CA (5.3%) compared to 3D Med tissue database (median age 55) including 260 samples with TP53 (74.2%), AR (6.9%), KRAS (24.6%) NOTCH2 (11.5%) and PIK3CA (3.8%). In TCGA database including 587 patients with early stage diseases, the frequencies of the commonly altered genes detected in ctDNA were largely different with TP53 (65.9%), AR (1.0%), KRAS (1.0%), NOTCH2 (1.2%) and PIK3CA (2.6%). Alterations in five DNA damage repair associated-genes including BRCA1, BRCA2, ATM, ATR, RAD50 and CHEK2 were detected in 14.5% (11/76) of patients in ctDNA database compared to 19.2% (50/260) of patients in 3D Med tissue database and 12.6% (74/587) of patients in TCGA database.
Conclusions
Our results suggest that genomic profiling of ctDNA could detected GAs in a significant subset of patients with ovarian cancer. Hybrid capture- NGS based ctDNA liquid biopsy has the potential capability to serve as an alternative to tissue biopsy and further studies are warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
NanJing GaoChun People’s Hospital.
Funding
Has not received any funding.
Disclosure
Y. Zhang: Full / Part-time employment: 3D Medicines Inc. S. Cai: Full / Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.
Resources from the same session
1109 - First Canadian Interim Analysis from the Phase IIIb CompLEEment-1 Ribociclib + Letrozole HR+ HER2- Advanced Breast Cancer Trial
Presenter: Cristiano Ferrario
Session: Poster Display session 2
Resources:
Abstract
4401 - Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the US
Presenter: Jonathan Kish
Session: Poster Display session 2
Resources:
Abstract
5876 - Palbociclib-Fulvestrant (PALBO-FUL) and Everolimus -Exemestane (EVE-EXE) for Second line Hormonal Treatment (HT) of Metastatic Breast Cancer (MBC) with Lobular Histology: a Propensity Score Matched Analysis of a Multicenter ‘Real-World’ Patients (pts) Series.
Presenter: Armando Orlandi
Session: Poster Display session 2
Resources:
Abstract
3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Presenter: E Dees
Session: Poster Display session 2
Resources:
Abstract
5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)
Presenter: Sacha Howell
Session: Poster Display session 2
Resources:
Abstract
1475 - Alpelisib (ALP) + Fulvestrant (FUL) in Hormone-Receptor Positive (HR+), Human Epidermal Growth Factor Receptor-2–Negative (HER2–) Advanced Breast Cancer (ABC): Subgroup Analysis by Presence of Visceral Metastasis (VM) in the SOLAR-1 Trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3787 - A Phase I study of XZP-3287, a novel oral CDK4/6 Inhibitor, administered on a continuous dosing schedule, in patients with advanced solid tumours
Presenter: Binghe Xu
Session: Poster Display session 2
Resources:
Abstract
4835 - Phase-I dose-escalation and expansion study of the PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
Presenter: Huiping Li
Session: Poster Display session 2
Resources:
Abstract
5083 - Phase 2 study of DHP107 (Liporaxel®, oral paclitaxel) in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)
Presenter: Jin-Hee Ahn
Session: Poster Display session 2
Resources:
Abstract