Impact of molecular profiling on survival in patients with advanced biliary tract cancers

Biliary tract cancers (BTC) are a group of rare cancers (intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], and gallbladder carcinoma [GBC]) that are epidemiologically, etiologically, clinically, and pathologically heterogeneous. Due to late diagnosis, their prognosis remains dismal, and therapeutic options are limited. At the molecular level, BTC harbor distinct patterns with respect to the primary tumor location, with ICC being particularly rich in molecular alterations that may be actionable. The aim of this work was to determine whether receiving a molecularly targeted agent (MTA) according to an identified molecular alteration was associated with better overall survival (OS) compared to conventional treatments in patients with advanced BTC.

We conducted a retrospective study of all patients with advanced BTC who had tumor molecular profiling in our center between January 2015 and December 2021. Molecular alterations were categorized for their actionability according to the ESCAT scale of the European Society of Medical Oncology (ESMO) [1]. Patients were categorized into three groups: patients with targetable alterations (TA) and access to MTA (group 1); patients with TA who did not have access to MTA (group 2); and patients without TA (group 3). We compared OS (study primary endpoint) between the 3 groups using the Kaplan-Meier method. We analyzed the influence of potential confounding factors using a Cox model. We compared the growth modulation index (GMI; ratio between the time to progression (TTP) under MTA and the TTP of the previous line of treatment, a GMI ≥1.33 indicating a clinically relevant benefit [2]) in group 1 vs groups 2 and 3 pooled.

Of the 546 patients with BTC (iCC, 60.7%) registered in our center between 2015 and 2021, 313 (57.3%) had at least one molecular profile performed. At least one TA was identified in 146 patients (46.6%), of which 77 (52.7%) of the 146 patients (24.6% of the 313 patients profiled and 14.1% of all 546 patients) received one or more MTAs (group 1). Median OS was 28.0 months (95% confidence interval (CI), 24.8–36.7) in group 1, 18.0 months (15.4–26.3) in group 2 (HR, 1.94 [1.32-2.85]; p < 0.001), and 21.0 months (19–24.8) in group 3 (HR, 1.62 [1.18–2.23]; p = 0.003). A GMI ≥1.33 was observed in 33 patients (49% [39%-63%]) in the group 1, compared with 48 patients (33%; [26%-43%]) in groups 2+3 (p = 0.02).

Identifying and categorizing TAs as per ESCAT classification and administering MTAs accordingly is associated with a longer OS in patients with advanced BTC.

The authors.

Has not received any funding.

A. Hollebecque: Honoraria (Institution): Astra-Zeneca, Roche; Advisory / Consultancy: Abbvie, Amgen, Basilea, BMS, Incyte, Servier, QED therapeutics, Relay Therapeutics, Seagen, Taiho; Research grant / Funding (self): Incyte; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: AstraZeneca. All other authors have declared no conflicts of interest.