Real-world assessment of MDM2 amplification and survival among patients with advanced or metastatic biliary tract cancer in the United States.

544 Background: There are few real-world studies on biliary tract cancer (BTC), especially those related to biomarkers for potential novel targeted therapies. The aim of this study was to provide additional information of the prevalence of biomarkers, treatment patterns, and clinical outcomes of patients with BTC in the US, with a focus on patients with mouse double minute 2 homolog ( MDM2 ) amplified, tumor protein 53 wild type (TP53 WT) BTC. Methods: This was an observational cohort study using deidentified data from the Flatiron Health-Foundation Medicine BTC Clinico-Genomic Database, which included patients with advanced or metastatic BTC who underwent genomic analysis and received antineoplastic therapy in the US between January 1, 2013 and June 30, 2023. Three cohorts were created: 1) 1L+ cohort that included all patients that initiated 1 st line (1L) therapy during the study period, 2) 2L+ cohort that included all patients that initiated 2 nd line (2L) therapy during the study period, and 3) MDM2 amp + TP53 WT cohort that included patients in the 1L+ cohort that had MDM2 amplified (≥ 8 copies), TP53 WT. The prevalence of select biomarkers was assessed, as well as treatment patterns, and clinical outcomes including time to next therapy (TTNT) and overall survival (OS). Results: A total of 1,548 patients met the selection criteria for the 1L+ cohort, of whom, 875 initiated 2L therapy (2L+ cohort), and 55 had MDM2 amplified, TP53 WT BTC ( MDM2 amp + TP53 WT cohort). In the 1L+ cohort, 66 (4.3%) had MDM2 amplification and 872 (56.3%) had TP53 WT. The most common treatment regimens were cisplatin/gemcitabine (44.5%, 50.7%, 41.8% of patients in the 1L+, 2L+, and MDM2 amp + TP53 WT cohorts, respectively) at 1L and FOLFOX (12.9%, 22.9%, 16.4% of patients, respectively) at 2L. The median (95% CI) OS from start of 1L was 10.7 (10.0 – 11.3) months for the 1L+ cohort and 11.9 (10.4 – 17.7) months for the MDM2 amp + TP53 WT cohort. The median OS from the start of 2L was 8.0 (7.2 – 8.8) months for 2L+ cohort. Furthermore, the median TTNT was similar between 1L+ cohort and MDM2 amp + TP53 WT cohort, 5.3 (5.0 – 5.7) and 4.8 (4.0 – 7.6) months, respectively. The median TTNT from the start of 2L in the 2L+ cohort was 4.3 (3.8 – 4.6) months. We will present co-mutation data in MDM2 amp + TP53 WT cohort. Conclusions: The MDM2 amplification and TP53 WT status does not appear to be a prognostic biomarker in advanced/metastatic BTC with similar median TTNT and OS in the 1L+ and MDM2 amp + TP53 WT cohorts. Targeted treatments may help improve OS among these patients and thus further research into these treatments and how they impact survival is warranted.