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

Autor: Rimini M; IRCCS San Raffaele Scientific Institute Hospital, Vita-Salute San Raffaele University, Milan, Italy. margherita.rimini@gmail.com.; Department of Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy. margherita.rimini@gmail.com., Loi E; Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Cagliari, Italy., Rizzato MD; Department of Oncology, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy., Pressiani T; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy., Vivaldi C; Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy., Gusmaroli E; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Antonuzzo L; Clinical Oncology Unit, Careggi University Hospital, Florence, Italy.; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Martinelli E; Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy., Garajova I; Medical Oncology Unit, University Hospital of Parma, Parma, Italy., Giordano G; Unit of Medical Oncology and Biomolecular Therapy, Policlinico Riuniti, Foggia, Italy.; Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy., Lucchetti J; Division of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy., Schirripa M; Medical Oncology Unit, Department of Oncology and Hematology, Central Hospital of Belcolle, Strada Sammartinese Snc, Viterbo, Italy., Cornara N; Department of Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy., Rossari F; Department of Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy., Vitiello F; Department of Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy., Amadeo E; Department of Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy., Persano M; Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Cagliari, Italy., Piva VM; Department of Oncology, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy., Balsano R; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy., Salani F; Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.; Institute of Interdisciplinary Research 'Health Science', Scuola Superiore Sant'Anna, Pisa, Italy., Pircher C; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Cascinu S; IRCCS San Raffaele Scientific Institute Hospital, Vita-Salute San Raffaele University, Milan, Italy.; Department of Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy., Niger M; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Fornaro L; Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Rimassa L; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Milan, Italy., Lonardi S; Department of Oncology, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy., Scartozzi M; Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Cagliari, Italy., Zavattari P; Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Cagliari, Italy., Casadei-Gardini A; IRCCS San Raffaele Scientific Institute Hospital, Vita-Salute San Raffaele University, Milan, Italy.; Department of Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy.
Jazyk: angličtina
Zdroj: Targeted oncology [Target Oncol] 2024 Mar; Vol. 19 (2), pp. 223-235. Date of Electronic Publication: 2024 Feb 12.
DOI: 10.1007/s11523-024-01032-5
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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