MDM2 amplification in a real-world cohort of patients with biliary tract cancer from the Spanish RETUD gastrointestinal registry

Abstract

Background Antagonist of mouse double minute 2 homolog (MDM2) represents a novel therapeutic strategy in biliary tract cancer (BTC). We aimed to characterize the epidemiology of MDM2 amplifications in patients with BTC, associations of MDM2 with other genetic alterations, and survival outcomes. Materials and methods A real-world cohort of patients diagnosed with BTC (1 January 2017 to 31 December 2022) was evaluated (RETUD NCT06711211). Next-generation sequencing (NGS) testing was carried out. Demographic and clinical characteristics, molecular profile, treatments, and effectiveness [overall response rate (ORR) and survival outcomes] were assessed. Progression-free survival (PFS), overall survival (OS), and ORR were estimated for patients receiving first-line therapy, using the Kaplan–Meier method. Descriptive analyses were used to assess demographic, clinical, and molecular features. Results A total of 301 patients were included. MDM2 amplification was reported in 19 patients (6.3%); two of them (10.5%) had TP53 mutations. Most patients (63.2%; 12/19) with MDM2 amplification had intrahepatic tumors. However, MDM2 amplification was more frequent in patients with gall-bladder carcinoma (12.9%; 4/31). Patients with/without MDM2 amplification receiving first-line therapy [cisplatin and gemcitabine (CisGem)] showed a median OS [95% confidence interval (CI)] of 18.4 months (12.3-19.9 months) and 17.8 months (12.3-19.9 months, P = 0.247), a median PFS (95% CI) of 5.3 months (2.7-8.9 months) and 6.0 months (5.3-6.8 months, P = 0.423), and an ORR of 21.4% and 29.6% (P = 0.762), respectively. Conclusions Incidence of MDM2 amplification was similar to that described in other BTC cohorts. Comparable results in demographic/clinical characteristics, molecular profile, and survival outcomes between patients with/without MDM2 amplification was observed.