Abstract 301P
Background
This study aims to molecularly characterize a multicentric real-world cohort of biliary tract cancers (BTC) patients, with focus on genomic alterations within homologous recombination repair (HRR) genes.
Methods
We performed a retrospective analysis in patients with BTC treated at five Austrian centers and one German comprehensive cancer center between 2011 and 2023. Genomic variants were assessed using targeted DNA-based assays (MAPK-TRON NGS panel, AmoyDx HRD), RNA-based assays (FusionPlex CTL Panel, Archer), or integrated DNA/RNA platforms (TruSight Tumor 170, GeneRead DNAseq Custom Panel V2, FoundationOne CDx). Clinical endpoints, such as progression-free survival (PFS) and overall survival (OS) following platinum-based first-line chemotherapy, were correlated with HRR status using the log-rank test and Cox Regression.
Results
256 patients with molecular characterization were identified, of whom 243 received at least one palliative regimen. Regarding HRR genes, 176 patients exhibited no mutations (non-HRRm), while 67 demonstrated alterations in HRR genes (HRRm). Both groups were well balanced for clinical characteristics, with the majority (200 patients) receiving platinum-based first-line chemotherapy. HRRm patients exhibited numerically prolonged time to failure of strategy (TFS) (HR 0.89, 95%CI: 0.654-1.226, p= 0.49) and improved overall survival (OS) (HR 0.64, 95%CI 0.442-0.933, P=0.02). A trend for a clinical benefit of second-line therapy with re-exposure to platinum-based agents as compared to irinotecan-based regimens was observed (HR= 0.79, 95%CI 0.34-1.8, P= 0.56). In particular, we observed a trend for a better outcome for HRRm vs non-HRRm patients treated with irinotecan-based regimen in 2nd line (HR= 0.79, 95%CI 0.34-1.8, P= 0.56). A statistically significant interaction between HRRm status and the application of molecular informed therapeutic strategies in later lines was noted.
Conclusions
Platinum-based chemotherapy associates with more favorable outcomes in HRRm BTC patients. Further investigation is needed to delineate HRD in the context of personalizing systemic therapies of BTC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Kasper-Virchow: Other, Personal, Invited Speaker: Merck Serono, MSD, Novartis, BMS, Amgen, Roche, Lilly, Sanofi-Aventis, Incyte, Pierre Fabre. R.W. Hamacher: Financial Interests, Personal, Other: Lilly, PharmaMar, Novartis. A.L. Petzer: Financial Interests, Personal, Advisory Role: Merck Serono, Bristol Myers Squibb, AstraZeneca, Novartis, PharmaMar, MSD, Janssen, Boehringer Ingelheim, Amgen, GSK, Roche, Sanofi, Amgen. J.T. Siveke: Financial Interests, Personal and Institutional, Advisory Role: Bristol Myers Squibb, Celgene; Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Immunocore, Roche; Financial Interests, Personal and Institutional, Leadership Role: Pharma15. All other authors have declared no conflicts of interest.