MDM2 is a key negative regulator of TP53 and, therefore, has become a target of interest in the treatment of patients with biliary tract cancer (BTC). However, no targeted treatments are currently available for patients with MDM2-amplified BTC. A recent real-world study, presented at the 2025 ASCO Gastrointestinal Cancers Symposium, investigated the treatment patterns and clinical outcomes of patients with advanced BTC, specifically with MDM2-amplified, TP53 wild-type (WT) disease.
The study retrospectively analyzed real-world data from the Flatiron Health-Foundation Medicine database, linking clinical and genomic data. Eligible patients received at least 1 line of therapy for advanced or metastatic BTC and had available genomic profiling results. Patients were categorized into 3 cohorts: patients who initiated first-line therapy during the study period (1L+ cohort), patients who initiated second-line therapy during the study period (2L+ cohort), and patients in the 1L+ cohort who had MDM2-amplified, TP53 WT disease (MDM2-amp + TP53 WT, 1L+ cohort).
A total of 1548 patients met criteria for the 1L+ cohort, 875 of those initiated second-line therapy (2L+ cohort) and 55 had MDM2-amplified, TP53 WT disease. In the 1L+ cohort, 4.3% of patients had MDM2-amplified disease and 56.3% were TP53 WT. TP53 mutations were detected in 43.8% of the 1L+ cohort and 44.1% of the 2L+ cohort. STK11/LKB1 mutations were detected in 21.8% of patients in the MDM2-amp + TP53 WT 1L+ cohort.
The most common first-line regimen in all 3 cohorts was cisplatin + gemcitabine, and the most common second-line regimen in all 3 cohorts was FOLFOX. The median time to next treatment (TTNT) was 5.3 months for the 1L+ cohort, 4.3 months in the 2L+ cohort (from start of second-line therapy), and 4.8 months in the MDM2-amp + TP53 WT 1L+ cohort.
The median overall survival (mOS) from the start of first-line therapy was 10.7 months in the 1L+ cohort and 11.9 months in the MDM2-amp + TP53 WT 1L+ cohort. The mOS from the start of second-line therapy in the 2L+ cohort was 8.0 months.
Although this study was limited by the real-world nature of the data, results indicate that MDM2- amplified, TP53 WT disease does not appear to be a prognostic biomarker in patients with advanced BTC. There was a similar TTNT and mOS in the 1L+ cohort and the MDM2-amp + TP53 WT 1L+ cohort. Further research is warranted for this patient population to understand how treatment may impact survival.
Lyer R, Evans K, Klein AB, et al. Real-world assessment of MDM2 amplification and survival among patients with advanced or metastatic biliary tract cancer in the United States. Presented at: ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA; Virtual. Poster 544.
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