The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine, and durvalumab: a large, real-life, worldwide population.
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Rimini Margherita, Fornaro Lorenzo, Lo Prinzi Federica, Rizzato Mario Domenico, Saborowski Anna, Antonuzzo Lorenzo, Rossari Federico, Satake Tomoyuki, Peeters Frederik, Vivaldi Caterina, Pressiani Tiziana, Lucchetti Jessica, Kim Jin Won, Abidoye Oluseyi, Rapposelli Ilario Giovanni, Tamberi Stefano, Finkelmeier Fabian, Giordano Guido, Nichetti Federico, Jae Chon Hong, Braconi Chiara, Qaisar Aitzaz, Pirrone Chiara, Castet Florian, Tamburini Emiliano, Yoo Changhoon, Parisi Alessandro, Diana Anna, Scartozzi Mario, Prager Gerald W, Avallone Antonio, Corallo Salvatore, Schirripa Marta, Kim Il Hwan, Perkhofer Lukas, Oneda Ester, Verrico Monica, Adeva Jorge, Chan Stephen L, Spinelli Gian Paolo, Personeni Nicola, Garajova Ingrid, Rodriquenz Maria Grazia, Leo Silvana, Alvim Cecilia Melo, Roque Ricardo, Farinea Giovanni, Salani Francesca, De Rosa Antonio, Lavacchi Daniele, Camera Silvia, Ikeda Masafumi, Dekervel Jeroen, Niger Monica, Balsano Rita, Tonini Giuseppe, Kang Minsu, Bekaii-Saab Tanios, Esposito Luca, Boccaccino Alessandra, Himmelsbach Vera, Landriscina Matteo, Djaballah Selma Ahcene, Zanuso Valentina, Malapelle Umberto, Pepe Francesco, Masi Gianluca, Vogel Arndt, Lonardi Sara, Rimassa Lorenza, Casadei-Gardini Andrea
Аннотация
METHODS: Patients with unresectable, locally advanced, or metastatic biliary tract cancer treated with cisplatin and gemcitabine plus durvalumab across 39 centers in 11 countries in Europe, the United States, and Asia were included in this analysis.
RESULTS: The cohort included 513 patients with advanced biliary tract cancer. The 5 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) (hazard ratio [HR] = 0.49, P = .018) and overall survival (HR = 0.11, P = .023), while TP53 mutations were linked to worse PFS (HR = 1.62, P = .0047) and TERT mutations to worse overall survival (HR = 8.92, P = .0012). No other genomic alterations were statistically associated with outcomes. Subgroup analysis showed that TP53 mutations negatively affected PFS and overall survival in intrahepatic cholangiocarcinoma, while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma. 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 overall survival and highlights the negative prognostic roles of TP53 (PFS) and TERT (overall survival) mutations, providing valuable insights for personalized treatment strategies in biliary tract cancer.