Abstract 163P
Background
Next generation sequencing (NGS) technologies allow for a better understanding of tumors’ biology and the implementation of targeted therapy (TT). We conducted a prospective investigational project at the Catalan Institut of Oncology-Badalona to assess their clinical utility in ABC.
Methods
After obtaining the informed consent of patients (pts) with ABC, Oncomine Comprehensive AssayV3 and the Intrinsic subtype (IS) by Prosigna were applied to analyze genomic profile including mutations (mut) and copy number variants (CNV) of 161 genes. We evaluated clinical and molecular characteristics, TT and the impact of molecular alterations (alt) on treatment decision.
Results
Since November 2021, 64 pts were included, with evaluable genomic results in 54 (29 metastasis and 25 primary tumors). Median age was 59y (37-82). Twenty-three out of 53 (43.4%) pts with hormonal receptor (HR) positive HER2-negative ABC had been treated with >1 line (L) hormone therapy. Thirty-three pts (51.6%) had not received any prior chemotherapy L, 18 (28.1%) 1L, and 13 (20.3%) 2L. The IS distribution was 24 (44.4%) luminal B, 20 (37%) luminal A, 5 HER2-enriched, 5 basal-like (9.3% each), concordant with surrogate subtypes by IHQ in 70.6 %. More than 60 molecular alt were identified in 35 genes (median of 2 alt/patient); 1) mut: 21 (38.8 %) in PI3KCA (84.2% in HR+/HER2- tumors) and 17 (31.5%) in TP53 and 2) CNVs: 14 (25.9%) in FGFR1 and 13 in FGF19 (24%), 12 in CCND1 and ERBB2 (17.7% each). PI3KCA-mut was associated with a lower incidence of other alt compared to non-mut tumors (15 vs 52 additional alt, respectively: Chi-square, p=0.001). Six pts had died at the time of analysis with a median Overall Survival (OS) of 3.4 years. Triple Negative ABC, TP53 and PTEN mut were independently associated with worse progression free survival to 1L and OS (p<0.001). To date, 6 pts (11.1%) have received TT, mainly for PI3KCA mut and up to 25 (39.1%) will be considered for TT at progression.
Conclusions
Based on NGS data, more than 10% of pts benefitted from targeted therapy at the time of analysis, with expected benefit for additional 20%. Noteworthy, NGS adds prognostic information and better selection of sequential therapies. NGS is a key tool for personalised therapies in ABC, requiring more research to optimize its use.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
Hospital Germans Trias i Pujol.
Disclosure
M.A. Bergamino: Non-Financial Interests, Personal, Invited Speaker: Eisai; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Funding: Novartis.M. Romeo Marin: Financial Interests, Personal, Funding: GSK, AstraZeneca, Clovis, MSD. M. Margeli Vila: Financial Interests, Personal, Funding: Novartis, Pfizer, Lilly, Gilead, Pierre Fabre, MSD. All other authors have declared no conflicts of interest.
Resources from the same session
134P - Doxorubicin and olaparib (OLA) synergism in high-grade serous ovarian (HGOC) and triple-negative breast cancer (TNBC) cell lines with olaparib-resistance
Presenter: Jose Alejandro Perez Fidalgo
Session: Cocktail & Poster Display session
Resources:
Abstract
136P - Molecular correlates of drug response to guide therapy in TNBC
Presenter: Nathan Merrill
Session: Cocktail & Poster Display session
Resources:
Abstract
137P - Event-free survival prediction using lncRNAs in pediatric B-cell acute lymphoblastic leukemia
Presenter: Unai Illarregi
Session: Cocktail & Poster Display session
Resources:
Abstract
138P - Exome sequencing analysis for the identification of actionable mutations related to neoadjuvant chemotherapy response in locally advanced breast cancer
Presenter: Ximena López
Session: Cocktail & Poster Display session
Resources:
Abstract
139P - Genomic prognostic and potential theragnostic factors in anal squamous cell carcinoma treated with abdominoperineal resection
Presenter: Abderaouf Hamza
Session: Cocktail & Poster Display session
Resources:
Abstract
144P - Correlation of EZH2 expression and response to chemoradiotherapy in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers
Presenter: Soel Ahmed
Session: Cocktail & Poster Display session
Resources:
Abstract
140P - Predictive value of DNA damage response and repair gene alterations and neoscore for neoadjuvant immunotherapies in non-small cell lung cancer
Presenter: Fei Feng
Session: Cocktail & Poster Display session
Resources:
Abstract
141P - Immune-related epigenomic and transcriptomic signatures to predict immunotherapy response in NSCLC
Presenter: María Gallardo-Gómez
Session: Cocktail & Poster Display session
Resources:
Abstract
142P - Role and impact of hypoxia-inducible factor 1-alpha on survival rates in pancreatic cancer: A systematic review and meta-analysis
Presenter: Muhammed Elfaituri
Session: Cocktail & Poster Display session
Resources:
Abstract
143P - Genomic characterization and outcomes of patients with primary sclerosing cholangitis-related cholangiocarcinoma
Presenter: Jaime Haro Silerio
Session: Cocktail & Poster Display session
Resources:
Abstract