Citations 2
The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine, and durvalumab: a large, real-life, worldwide population
Prinzi, Federica Lo , Rizzato, Mario Domenico , Saborowski, Anna , Antonuzzo, Lorenzo , Rossari, Federico , Satake, Tomoyuki, Peeters, Frederik , Pressiani, Tiziana , Finkelmeier, Fabian , Braconi, Chiara , Qaisar, Aitzaz, Pirrone, Chiara, Castet, Florian , Parisi, Alessandro , Scartozzi, Mario, Corallo, Salvatore , Perkhofer, Lukas , Adeva, Jorge , Spinelli, Gian Paolo , Rodriquenz, Maria Grazia , Leo, Silvana, Alvim, Cecilia Melo, Roque, Ricardo , Salani, Francesca , Rosa, Antonio De, Lavacchi, Daniele, Dekervel, Jeroen , Niger, Monica, Balsano, Rita , Esposito, Luca, Boccaccino, Alessandra , Himmelsbach, Vera, Zanuso, Valentina , Vogel, Arndt, Rimassa, Lorenza , Casadei‐Gardini, Andrea , Vogel, Arndt , Lo Prinzi, Federica , Rizzato, Mario Domenico , Saborowski, Anna , Antonuzzo, Lorenzo , Rossari, Federico , Peeters, Frederik , Pressiani, Tiziana , Lucchetti, Jessica , Kim, Jin Won , Abidoye, Oluseyi , Rapposelli, Ilario Giovanni , Finkelmeier, Fabian , Giordano, Guido , Nichetti, Federico , Jae Chon, Hong , Qaisar, Aitzaz , Pirrone, Chiara , Castet, Florian , Tamburini, Emiliano , Parisi, Alessandro , Scartozzi, Mario , Avallone, Antonio , Corallo, Salvatore , Schirripa, Marta , Oneda, Ester , Verrico, Monica , Adeva, Jorge , Chan, Stephen L , Spinelli, Gian Paolo , Personeni, Nicola , Garajova, Ingrid , Rodriquenz, Maria Grazia , Roque, Ricardo , Farinea, Giovanni , Salani, Francesca , De Rosa, Antonio , Camera, Silvia , Ikeda, Masafumi , Dekervel, Jeroen , Niger, Monica , Kang, Minsu , Bekaii-Saab, Tanios S , Esposito, Luca , Boccaccino, Alessandra , Djaballah, Selma Ahcene , Zanuso, Valentina , Masi, Gianluca , Vogel, Arndt , Lonardi, Sara , Rimassa, Lorenza , Casadei-Gardini, Andrea , Casadei-Gardini, Andrea , Rimini, Margherita , Fornaro, Lorenzo , Vivaldi, Caterina , Kim, Jin Won , Abidoye, Oluseyi , Tamberi, Stefano , Nichetti, Federico , Chon, Hong Jae , Yoo, Changhoon , Diana, Anna , Prager, Gerald W. , Kim, Il Hwan , Chan, Stephen L. , Ikeda, Masafumi , Niger, Monica , Tonini, Giuseppe , Bekaii‐Saab, Tanios , Landriscina, Matteo , Malapelle, Umberto , Pepe, Francesco , Lonardi, Sara
JNCI: Journal of the National Cancer Institute | July 3, 2025 | Volume: 117 | Issue: 10 | Pages: 2029-2043
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.
Efficacy of cisplatin-gemcitabine-durvalumab in patients with advanced biliary tract cancer experiencing early vs late disease relapse after surgery: a large real-life worldwide population
Prinzi, Federica Lo , Salani, Francesca , Antonuzzo, Lorenzo , Satake, Tomoyuki, Vandeputte, Hanne, Pressiani, Tiziana , Finkelmeier, Fabian , Pircher, Chiara , Braconi, Chiara , Pastorino, Alessandro , Castet, Florian , Parisi, Alessandro , Perkhofer, Lukas , Adeva, Jorge , Spinelli, Gian Paolo , Rodriquenz, Maria Grazia , Leo, Silvana, Alvim, Cecilia Melo, Roque, Ricardo , Rosa, Antonio De, Lavacchi, Daniele, Dekervel, Jeroen , Balsano, Rita , Viola, Massimo, Silvestro, Lucrezia , Boccaccino, Alessandra , Himmelsbach, Vera, Zanuso, Valentina , Rimassa, Lorenza , Casadei‐Gardini, Andrea , Lo Prinzi, Federica , Abidoye, Oluseyi , Parisi, Alessandro , Ikeda, Masafumi , Antonuzzo, Lorenzo , Casadei-Gardini, Andrea , Finkelmeier, Fabian , Castet, Florian , Adeva, Jorge , Rimassa, Lorenza , Casadei-Gardini, Andrea , Pressiani, Tiziana , Roque, Ricardo , Salani, Francesca , De Rosa, Antonio , Dekervel, Jeroen , Rimini, Margherita , Rizzato, Mario Domenico , Camera, Silvia , Vivaldi, Caterina , Lucchetti, Jessica , Kim, Jin Won , Rapposelli, Ilario Giovanni , Tamberi, Stefano , Giordano, Guido , Chon, Hong Jae , Tamburini, Emiliano , Yoo, Changhoon , Diana, Anna , Scartozzi, Mario , Prager, Gerald W. , Avallone, Antonio , Schirripa, Marta , Kim, Il Hwan , Oneda, Ester , Verrico, Monica , Chan, Stephen L. , Personeni, Nicola , Garajova, Ingrid , Fornaro, Lorenzo , Rossari, Federico , Ikeda, Masafumi , Niger, Monica , Tonini, Giuseppe , Kang, Minsu , Bekaii‐Saab, Tanios , Esposito, Luca , Landriscina, Matteo , Djaballah, Selma Ahcene , Masi, Gianluca , Lonardi, Sara
The Oncologist | September 6, 2024 | Volume: 30 | Issue: 3 | Pages: No page available
Abstract Background In the TOPAZ-1, patients with biliary tract cancers (BTC) and recurrence within 6 months after surgery were excluded, even if this event is frequently observed in clinical practice. Our study aimed to assess if the efficacy of cisplatin-gemcitabine-durvalumab (CGD) in this population is comparable to that reported in the phase 3 trial. Methods The study cohort included patients with BTC who underwent surgery on the primary tumor, experienced disease recurrence occurring ≤6 months or >6 months after surgery or after the end of adjuvant therapy and started CGD. The primary objectives were overall survival (OS) and progression free survival (PFS). Results A total of 178 patients were enrolled. No significant differences were observed between early and late relapse groups in OS (23.4 months vs not reached; HR 1.26; 95% CI, 0.67-2.37; P = .45) and PFS [7.0 months vs 9.8 months; HR 1.3(95% CI, 0.9-2.1) P = .13]. Overall response rate and disease control rate (P = .33 and P = .62) were comparable between the 2 groups, as the overall safety profile. In addition, we compared survival outcomes between the selected population and a historical cohort of patients with BTC treated with cisplatin-gemcitabine (CG) and found that despite the absence of statistical significance, CGD showed an outcome trend compared with CG regardless of the time of recurrence after surgery or adjuvant chemotherapy [(CG ≤ 6 vs CGD ≤ 6 months: HR 0.59, 95%CI, 0.35-1.01, P = .05; HR 0.70; 95%CI, 0.46-1.06, P = .09, OS and PFS, respectively) and (CG > 6 vs. CGD > 6 months: HR 0.50; 95%CI, 0.29-0.88, P = 0.0165; HR 0.54; 95%CI, 0.35-0.84, P = .0068, OS and PFS, respectively)]. Conclusion Our analysis suggests that CGD retains its efficacy independently of the timing of relapse after surgery or completion of adjuvant treatment in patients with advanced BTC.