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
Authors: Lo Prinzi Federica , Salani Francesca , Rimini Margherita , Rizzato Mario Domenico , Antonuzzo Lorenzo , Camera Silvia , Satake Tomoyuki , Vandeputte Hanne , Vivaldi Caterina , Pressiani Tiziana , Lucchetti Jessica , Kim Jin Won , Abidoye Oluseyi , Rapposelli Ilario Giovanni , Tamberi Stefano , Finkelmeier Fabian , Giordano Guido , Pircher Chiara , Chon Hong Jae , Braconi Chiara , Pastorino Alessandro , Castet Florian , Tamburini Emiliano , Yoo Changhoon , Parisi Alessandro , Diana Anna , Scartozzi Mario , Prager Gerald W , Avallone Antonio , 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 , Melo Alvim Cecilia , Roque Ricardo , Fornaro Lorenzo , De Rosa Antonio , Lavacchi Daniele , Rossari Federico , Ikeda Masafumi , Dekervel Jeroen , Niger Monica , Balsano Rita , Tonini Giuseppe , Kang Minsu , Bekaii-Saab Tanios , Viola Massimo Giuseppe , Silvestro Lucrezia , Esposito Luca , Boccaccino Alessandra , Himmelsbach Vera , Landriscina Matteo , Ahcene Djaballah Selma , Zanuso Valentina , Masi Gianluca , Lonardi Sara , Rimassa Lorenza , Casadei-Gardini Andrea 
Published: October 2024

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 &gt;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 &gt; 6 vs. CGD &gt; 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.