The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine, and durvalumab: a large, real-life, worldwide population
Academic Article
Publication Date:
2025
Short description:
The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine, and durvalumab: a large, real-life, worldwide population / Rimini, M., Fornaro, L., Lo Prinzi, F., Rizzato, M.D., Saborowski, A., Antonuzzo, L., Rossari, F., Satake, T., Peeters, F., Vivaldi, C., Pressiani, T., Lucchetti, J., Kim, J.W., Abidoye, O., Rapposelli, I.G., Tamberi, S., Finkelmeier, F., Giordano, G., Nichetti, F., Jae Chon, H., et al.. - In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - ISSN 0027-8874. - 117:10(2025), pp. 2029-2043. [10.1093/jnci/djaf155]
abstract:
Background Cisplatin, gemcitabine, and durvalumab combination is a standard first-line treatment for advanced biliary tract cancer. This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced biliary tract cancer treated with cisplatin, gemcitabine, and durvalumab in real-world clinical practice.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.
Iris type:
1.1 Articolo in rivista
List of contributors:
Rimini, M.; Fornaro, L.; Lo Prinzi, F.; Rizzato, M. D.; Saborowski, A.; Antonuzzo, L.; Rossari, F.; Satake, T.; Peeters, F.; Vivaldi, C.; Pressiani, T.; Lucchetti, J.; Kim, J. W.; Abidoye, O.; Rapposelli, I. G.; Tamberi, S.; Finkelmeier, F.; Giordano, G.; Nichetti, F.; Jae Chon, H.; Braconi, C.; Qaisar, A.; Pirrone, C.; Castet, F.; Tamburini, E.; Yoo, C.; Parisi, A.; Diana, A.; Scartozzi, M.; Prager, G. W.; Avallone, A.; Corallo, S.; Schirripa, M.; Kim, I. H.; Perkhofer, L.; Oneda, E.; Verrico, M.; Adeva, J.; Chan, S. L.; Spinelli, G. P.; Personeni, N.; Garajova, I.; Rodriquenz, M. G.; Leo, S.; Alvim, C. M.; Roque, R.; Farinea, G.; Salani, F.; De Rosa, A.; Lavacchi, D.; Camera, S.; Ikeda, M.; Dekervel, J.; Niger, M.; Balsano, R.; Tonini, G.; Kang, M.; Bekaii-Saab, T.; Esposito, L.; Boccaccino, A.; Himmelsbach, V.; Landriscina, M.; Djaballah, S. A.; Zanuso, V.; Malapelle, U.; Pepe, F.; Masi, G.; Vogel, A.; Lonardi, S.; Rimassa, L.; Casadei-Gardini, A.
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