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
113P - Evaluation of effects of tissue preservation methods on the proteome abundance through deep proteomics of breast cancer tissue
Presenter: Shashwati parihari
Session: Cocktail & Poster Display session
Resources:
Abstract
114P - Circulating microRNAs and response to oncological and surgical therapy in patients with locally advanced gastric cancer
Presenter: Vasileia Kokala-Dimitropoulou
Session: Cocktail & Poster Display session
Resources:
Abstract
115P - BrainStorm-NSE: Serum neuron-specific enolase as a biomarker for central nervous system metastases: A prospective cohort study
Presenter: Diogo Martins-Branco
Session: Cocktail & Poster Display session
Resources:
Abstract
116P - Switching to a multigenic parallel sequencing approach: The landscape of biomarkers profiling changing between immunohistochemistry and next generation sequencing advantages and sustainability from a public hospital in Northern Italy
Presenter: Giulia Ghirardi
Session: Cocktail & Poster Display session
Resources:
Abstract
117P - Homologous recombination deficiency (HRD) by shallow whole genome sequencing (sWGS): Seamless integration in an existing NGS somatic oncology workflow
Presenter: Etienne Muller
Session: Cocktail & Poster Display session
Resources:
Abstract
118P - Molecular diagnostics of gastrointestinal stromal tumors in the era of precision oncology
Presenter: Alena Kalfusova
Session: Cocktail & Poster Display session
Resources:
Abstract
119P - De novo and histologically transformed small-cell lung cancer is sensitive to lurbinectedin treatment through the modulation of EMT and NOTCH signaling pathways
Presenter: Triparna Sen
Session: Cocktail & Poster Display session
Resources:
Abstract
120P - Anti-angiogenic therapy or immunotherapy? A multicenter real-world study of patients with advanced non-small cell lung cancer with EGFR / HER2 exon 20 insertion mutations
Presenter: Tianqing Chu
Session: Cocktail & Poster Display session
Resources:
Abstract
121P - Clinical outcomes of compound EGFR mutation in non-small cell lung cancer: A national, retrospective, multicenter study
Presenter: Aurélien Brindel
Session: Cocktail & Poster Display session
Resources:
Abstract
122P - Molecular testing, treatment, and response of patients with advanced solid tumors harboring an NTRK gene fusion: Second interim results of the REALTRK registry
Presenter: Sebastian Lange
Session: Cocktail & Poster Display session
Resources:
Abstract