Abstract 1636P
Background
Pts with advanced PC have limited treatment (Tx) options. Research has focused on identifying a subset of pts who may benefit from targeted therapies. ctDNA genomic profiling by NGS is an emerging non-invasive diagnostic tool. We show the genomic landscape of advanced PC pts using ctDNA.
Methods
We conducted a retrospective multicentre analysis of PC pts that underwent ctDNA blood sample testing 10 days after any Tx line progression. Samples were analysed by standardised Guardant360 assay covering microsatellite instability (MSI) evaluation and somatic alterations among 74 genes reported as pathogenic or non-pathogenic. Hereditary syndromes genes with VAF ≥ 30% were confirmed by Sanger. Demographic data were obtained from medical records. Potential therapeutically relevant alterations (pTRA) were classified according to OncoKB and ESCAT levels of evidence (LE), consulted 05/2023. Negative ctDNA reports were interpreted as absence or low levels of detectable mutations (mut).
Results
We collected blood samples of 242 PC pts from 07/2017 to 08/2022 from 7 hospitals in Spain. Most pts were diagnosed with metastatic PC; 52% were male, 56% were <65 yrs. old and 45% were Tx naïve. Median turnaround for molecular reports was 6 days. A total of 736 gene alterations were detected, 78% pathogenic and 18% pTRA. Negative ctDNA was reported in 48 pts (20%). TP53 (67%) was the most frequently altered gene, followed by KRAS (62%). Additionally, we identified incidental germline cancer predisposition mut detected in 9 pts (4%), 3 ATM and 6 BRCA2. Description of pTRA according to OncoKB and ESCAT LE in the table. Only 4 (2%) pts with BRCA2 mut received PARP inhibitors Tx. Table: 1636P
Number of potential therapeutically relevant alterations according to OncoKB and ESCAT levels of evidence
| Pathogenic | Non-Pathogenic | OncoKB | ESCAT | |
| MSI-High | 2 | 0 | 1 | IC |
| BRAF V600E | 1 | 0 | 1 | IIIA |
| BRCA1 BRCA2 | 3 13 | 8 6 | 2 | Germline IA Somatic IIIB |
| KRAS G12C KRAS G12D | 2 18 | 0 0 | 3 4 | IIB IIIA |
| ARID1A | 15 | 9 | 4 | IVA |
| CDKN2A | 34 | 3 | 4 | IIIA |
| PIK3CA | 8 | 1 | 4 | IIIA |
| TP53 Y220C | 6 | 0 | 3 | IIIA |
| Others | 474 | 133 | - | - |
Conclusions
ctDNA is a feasible and non-invasive tool for identifying pTRA in advanced PC pts and adds value by detecting hereditary syndromes. Even though very few pts receives molecular targeted therapy. We highlight a clinical practice gap and the unmet medical need for new treatment options.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F.N. Riva: Financial Interests, Personal, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.
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