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12-02-2024 | Original Research Article

Different Genomic Clusters Impact on Responses in Advanced Biliary Tract Cancer Treated with Cisplatin Plus Gemcitabine Plus Durvalumab

Authors: Margherita Rimini, Eleonora Loi, Mario Domenico Rizzato, Tiziana Pressiani, Caterina Vivaldi, Eleonora Gusmaroli, Lorenzo Antonuzzo, Erika Martinelli, Ingrid Garajova, Guido Giordano, Jessica Lucchetti, Marta Schirripa, Noemi Cornara, Federico Rossari, Francesco Vitiello, Elisabeth Amadeo, Mara Persano, Vittoria Matilde Piva, Rita Balsano, Francesca Salani, Chiara Pircher, Stefano Cascinu, Monica Niger, Lorenzo Fornaro, Lorenza Rimassa, Sara Lonardi, Mario Scartozzi, Patrizia Zavattari, Andrea Casadei-Gardini

Published in: Targeted Oncology | Issue 2/2024

Abstract

Background

The results reported in the TOPAZ-1 phase III trial led to the approval of the combination of cisplatin and gemcitabine with durvalumab as the new first-line standard of care for patients with locally advanced or metastatic cholangiocarcinoma.

Objective

We performed a clustering analysis to classify patients into different groups based on their mutation profile, correlating the results of the analysis with clinical outcomes.

Methods

We selected 51 patients with cholangiocarcinoma who were treated with the combination of chemotherapy and durvalumab and who were screened using the next-generation sequencing-based FoundationOne gene panel. We conducted mutation-based clustering of tumors and a survival analysis.

Results

Three main clusters were identified. Cluster 1 is mostly characterized by mutations in genes belonging to the chromatin modification pathway, altered in 100% of patients. Cluster 2 is characterized by the alteration of several pathways, among which DNA damage control, chromatin modification, RTK/RAS, cell-cycle apoptosis, TP53, and PI3K were the most affected. Finally, most altered pathways in cluster 3 were RTK/RAS and cell-cycle apoptosis. Overall response rate was 4/13 (31%), 12/24 (50%), and 0/10 (0%) in cluster 1, cluster 2, and cluster 3, respectively, and the difference between the three clusters was statistically significant (p = 0.0188).

Conclusions

By grouping patients into three clusters with distinct molecular and genomic alterations, our analysis showed that patients included in cluster 2 had higher overall response rates, whereas patients included in cluster 3 had no objective response. Further investigations on larger and external cohorts are needed in order to validate our results.

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Title: Different Genomic Clusters Impact on Responses in Advanced Biliary Tract Cancer Treated with Cisplatin Plus Gemcitabine Plus Durvalumab
Authors: Margherita Rimini
Eleonora Loi
Mario Domenico Rizzato
Tiziana Pressiani
Caterina Vivaldi
Eleonora Gusmaroli
Lorenzo Antonuzzo
Erika Martinelli
Ingrid Garajova
Guido Giordano
Jessica Lucchetti
Marta Schirripa
Noemi Cornara
Federico Rossari
Francesco Vitiello
Elisabeth Amadeo
Mara Persano
Vittoria Matilde Piva
Rita Balsano
Francesca Salani
Chiara Pircher
Stefano Cascinu
Monica Niger
Lorenzo Fornaro
Lorenza Rimassa
Sara Lonardi
Mario Scartozzi
Patrizia Zavattari
Andrea Casadei-Gardini
Publication date: 12-02-2024
Publisher: Springer International Publishing
Published in: Targeted Oncology / Issue 2/2024
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-024-01032-5

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Abstract

Background

Objective

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Results

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