Comprehensive Examination of Cholangiocarcinoma Patients Treated with Novel Targeted Therapies after Extended Molecular Profiling on Liquid Biopsies.

Autor: Mahmood U; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK., Muhamad Faizul E; Faculty of Medical Sciences, University College London, London WC1E 6BT, UK., Howlett S; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK., Amin Z; Department of Radiology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK., Hochhauser D; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK.; University College London Cancer Institute, London WC1E 6DD, UK., Shiu KK; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK.; University College London Cancer Institute, London WC1E 6DD, UK., Bridgewater J; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK.; University College London Cancer Institute, London WC1E 6DD, UK., Khan K; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK.; University College London Cancer Institute, London WC1E 6DD, UK.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 Feb 06; Vol. 16 (4). Date of Electronic Publication: 2024 Feb 06.
DOI: 10.3390/cancers16040697
Abstrakt: Background: Cholangiocarcinoma (CCA) is associated with poor outcomes and limited treatment options, leading to increased use of targeted therapies for its management. Here, we performed one of the largest single-centre reviews evaluating outcomes following personalised targeted agents in CCA patients.
Methods: All consecutive CCA patients receiving systemic therapy between January 2010 and April 2023 at UCLH were included. The primary objective of this study was to evaluate treatment response, survival outcomes and predictors of clinical benefit in CCA patients treated with molecularly guided therapies. Patient demographic factors, disease characteristics and survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional-hazards models.
Results: Of the 227 consecutive CCA patients, 162 (71%) had molecular profiling, of whom 56 (35%) were eligible and 55 received molecular-targeted treatment. CCA histological classifications comprised intrahepatic (N = 32), extrahepatic (N = 11), hilar (N = 4) and unknown (N = 9) subtypes. Most patients received targeted agents based on genomic profiling in a second treatment line setting (N = 34). Frequently observed genomic alterations occurred in the FGFR2 (N = 21), IDH1 (N = 7) and BRCA2 (N = 6) genes. Median progression-free survival (PFS) following first-, second- and third-line systemic therapy and overall survival (OS) were 8.44 (95% CI, 7.49-12.78), 5.65 (95% CI, 3.71-7.13), 5.55 (2.79-12.58) and 29.01 (24.21-42.91) months, respectively. CCA subtype and FGFR/BRCA molecular aberration status were not associated with PFS or OS. However, a prior CCA-related surgical history was predictive of OS ( p = 0.02). Stratification by best overall response to second-line targeted agents demonstrated an association with PFS ( p = 0.002) and OS ( p = 0.02). Duration of treatment with second-line targeted therapy was associated with OS ( p < 0.001).
Conclusions: Patients receiving targeted therapeutics achieved promising outcomes, especially those attaining a favourable treatment response and those receiving targeted agents for longer periods. Liquid biopsies can reliably provide information on extended molecular profiling to aid patient selection for personalised therapies.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
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