The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine and durvalumab: a large real-life worldwide population.
Margherita Rimini, Lorenzo Fornaro, Federica Lo Prinzi, Mario Domenico Rizzato, Anna Saborowski, Lorenzo Antonuzzo, Federico Rossari, Tomoyuki Satake, Frederik Peeters, Caterina Vivaldi, Tiziana Pressiani, Jessica Lucchetti, Jin Won Kim, Oluseyi Abidoye, Ilario Giovanni Rapposelli, Stefano Tamberi, Fabian Finkelmeier, Guido Giordano, Federico Nichetti, Hong Jae Chon, Chiara Braconi, Aitzaz Qaisar, Chiara Pirrone, Florian Castet, Emiliano Tamburini, Changhoon Yoo, Alessandro Parisi, Anna Diana, Mario Scartozzi, Gerald W Prager, Antonio Avallone, Salvatore Corallo, Marta Schirripa, Il Hwan Kim, Lukas Perkhofer, Ester Oneda, Monica Verrico, Jorge Adeva, Stephen L Chan, Gian Paolo Spinelli, Nicola Personeni, Ingrid Garajova, Maria Grazia Rodriquenz, Silvana Leo, Cecilia Melo Alvim, Ricardo Roque, Giovanni Farinea, Francesca Salani, Antonio De Rosa, Daniele Lavacchi, Silvia Camera, Masafumi Ikeda, Jeroen Dekervel, Monica Niger, Rita Balsano, Giuseppe Tonini, Minsu Kang, Tanios Bekaii-Saab, Luca Esposito, Alessandra Boccaccino, Vera Himmelsbach, Matteo Landriscina, Selma Ahcene Djaballah, Valentina Zanuso, Umberto Malapelle, Francesco Pepe, Gianluca Masi, Arndt Vogel, Sara Lonardi, Lorenza Rimassa, Andrea Casadei-Gardini
{"title":"The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine and durvalumab: a large real-life worldwide population.","authors":"Margherita Rimini, Lorenzo Fornaro, Federica Lo Prinzi, Mario Domenico Rizzato, Anna Saborowski, Lorenzo Antonuzzo, Federico Rossari, Tomoyuki Satake, Frederik Peeters, Caterina Vivaldi, Tiziana Pressiani, Jessica Lucchetti, Jin Won Kim, Oluseyi Abidoye, Ilario Giovanni Rapposelli, Stefano Tamberi, Fabian Finkelmeier, Guido Giordano, Federico Nichetti, Hong Jae Chon, Chiara Braconi, Aitzaz Qaisar, Chiara Pirrone, Florian Castet, Emiliano Tamburini, Changhoon Yoo, Alessandro Parisi, Anna Diana, Mario Scartozzi, Gerald W Prager, Antonio Avallone, Salvatore Corallo, Marta Schirripa, Il Hwan Kim, Lukas Perkhofer, Ester Oneda, Monica Verrico, Jorge Adeva, Stephen L Chan, Gian Paolo Spinelli, Nicola Personeni, Ingrid Garajova, Maria Grazia Rodriquenz, Silvana Leo, Cecilia Melo Alvim, Ricardo Roque, Giovanni Farinea, Francesca Salani, Antonio De Rosa, Daniele Lavacchi, Silvia Camera, Masafumi Ikeda, Jeroen Dekervel, Monica Niger, Rita Balsano, Giuseppe Tonini, Minsu Kang, Tanios Bekaii-Saab, Luca Esposito, Alessandra Boccaccino, Vera Himmelsbach, Matteo Landriscina, Selma Ahcene Djaballah, Valentina Zanuso, Umberto Malapelle, Francesco Pepe, Gianluca Masi, Arndt Vogel, Sara Lonardi, Lorenza Rimassa, Andrea Casadei-Gardini","doi":"10.1093/jnci/djaf155","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & aims: </strong>Cisplatin, gemcitabine, and durvalumab (CGD) combination is a standard first-line treatment for advanced biliary tract cancer (BTC). This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced BTC treated with CGD in real-world clinical practice.</p><p><strong>Methods: </strong>Patients with unresectable, locally advanced, or metastatic BTC treated with CGD across 39 centers in 11 countries (Europe, United States, and Asia) were included in this analysis.</p><p><strong>Results: </strong>The cohort included 513 patients with advanced BTC. The five most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (HR 0.49, p = .018) and overall survival (OS) (HR 0.11, p = .023), while TP53 mutations were linked to worse PFS (HR 1.62, p = .0047) and TERT mutations to worse OS (HR 8.92, p = .0012). No other genomic alterations were significantly associated with outcomes.Subgroup analysis showed that TP53 mutations negatively impacted PFS and OS in intrahepatic cholangiocarcinoma (iCCA), while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma (eCCA). No gene alterations were linked to outcomes in gallbladder cancer.</p><p><strong>Conclusions: </strong>This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and OS and highlights the negative prognostic roles of TP53 (PFS) and TERT (OS) mutations, providing valuable insights for personalized treatment strategies in BTC.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JNCI Journal of the National Cancer Institute","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jnci/djaf155","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background & aims: Cisplatin, gemcitabine, and durvalumab (CGD) combination is a standard first-line treatment for advanced biliary tract cancer (BTC). This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced BTC treated with CGD in real-world clinical practice.
Methods: Patients with unresectable, locally advanced, or metastatic BTC treated with CGD across 39 centers in 11 countries (Europe, United States, and Asia) were included in this analysis.
Results: The cohort included 513 patients with advanced BTC. The five most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (HR 0.49, p = .018) and overall survival (OS) (HR 0.11, p = .023), while TP53 mutations were linked to worse PFS (HR 1.62, p = .0047) and TERT mutations to worse OS (HR 8.92, p = .0012). No other genomic alterations were significantly associated with outcomes.Subgroup analysis showed that TP53 mutations negatively impacted PFS and OS in intrahepatic cholangiocarcinoma (iCCA), while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma (eCCA). No gene alterations were linked to outcomes in gallbladder cancer.
Conclusions: This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and OS and highlights the negative prognostic roles of TP53 (PFS) and TERT (OS) mutations, providing valuable insights for personalized treatment strategies in BTC.
期刊介绍：
The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
