Outcomes of Cisplatin, Gemcitabine, and Durvalumab According to
TOPAZ
‐1 Study Eligibility: A Large Global Analysis in a Real‐World Setting
Federica Lo Prinzi, Margherita Rimini, Masafumi Ikeda, Oluseyi Abidoye, Jessica Lucchetti, Lorenzo Antonuzzo, Jin Won Kim, Federico Nichetti, Anna Saborowski, Tiziana Pressiani, Caterina Vivaldi, Ilario Giovanni Rapposelli, Frederik Peeters, Chiara Braconi, David J. Pinato, Emiliano Tamburini, Chiara Pircher, Stefano Tamberi, Florian Castet, Monica Verrico, Alessandro Parisi, Nuno Couto, Hong Jae Chon, Andrea Martirena, Angela Lamarca, Matteo Landriscina, Fabian Finkelmeier, Ester Oneda, Antonio Avallone, Emanuela Dell'Aquila, Lukas Perkhofer, Il Hwan Kim, Vincenzo Formica, Cidalia Maria de Sousa Pinto, Ingrid Garajova, Beodeul Kang, Salvatore Corallo, Elisabetta Fenocchio, Giovanni Farinea, Alessandro Pastorino, Anna Diana, Yoo Changhoon, Marta Schirripa, Maria Grazia Rodriquenz, Mario Scartozzi, Lucrezia Zumstein, Michele Ghidini, Gerald W. Prager, Giuseppe Aprile, Gian Paolo Spinelli, Su Yung‐Yeh, Stephen Lam Chan, Emily Warmington, Alessia Lancianese, Tomoyuki Satake, Tanios Bekaii‐Saab, Guido Giordano, Daniele Lavacchi, Laura Passeri, Michele Ferrara, Minsu Kang, Alessandra Anna Prete, Silvia Bozzarelli, Mara Persano, Gianluca Masi, Rita Balsano, Monica Niger, Sara Lonardi, Francesca Salani, Silvia Camera, Arndt Vogel, Lorenzo Fornaro, Lorenza Rimassa, Andrea Casadei‐Gardini ABSTRACT
Many real‐world patients with advanced biliary tract cancer (BTC) are excluded by TOPAZ‐1 criteria; this study assessed cisplatin and gemcitabine plus durvalumab (CGD) efficacy and safety in these patients. Data from 1358 patients with advanced BTC treated with first‐line CGD across 55 international centers were retrospectively analyzed. Patients were classified as TOPAZ‐1‐in (meeting all inclusion criteria) or TOPAZ‐1‐out (meeting ≥ 1 exclusion criterion). Primary endpoints were overall survival (OS) and progression‐free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Furthermore, OS and PFS of the TOPAZ‐1‐out cohort were compared with reconstructed survival data from the phase III trial. 912 (67.1%) patients were classified as TOPAZ‐1‐in , and 446 (32.9%) as TOPAZ‐1‐out . After a median follow‐up of 14.5 months (95% CI: 13.7–36.5), OS was 16.1 months in TOPAZ‐1‐in and 12.5 months in TOPAZ‐1‐out (HR 0.69, 95% CI: 14.6–16.5, p = 0.0001); PFS was 8.2 versus 6.5 months (HR 0.73, 95% CI: 7.1–8.1, p < 0.0001). Median OS in the TOPAZ‐1‐out cohort (12.5 months) was nearly identical to the phase III trial experimental arm (12.9 months; HR 1.15, p = 0.13); for PFS the HR was 1.12 (95% CI 0.93–1.42; p = 0.09). Among TOPAZ‐1‐out patients, active infection, elevated bilirubin, and ECOG PS > 1 were linked to poorer OS, while no detrimental impact emerged for ALT/AST abnormalities, corticosteroid use, renal or hematologic parameters, or prior surgery within 6 months, suggesting treatment effectiveness was broadly maintained across clinical subgroups. Furthermore, TOPAZ‐1‐out patients experienced no significant increase in adverse events compared with the TOPAZ‐1‐in group.
Real‐world data suggest CGD may be effective in TOPAZ‐1‐out patients, with no evident increase in toxicity, supporting the potential expanded use of the regimen in clinical practice.