Julien Edeline, Richard Jackson, Andrea Casadei-Gardini, Daniel Palmer, Arndt Vogel, Alexandre Peinoit, Jeanne Goetgheluck, Héloïse Bourien, Mairéad G McNamara, Samuel Le Sourd, Angela Lamarca, Margherita Rimini, Lorenzo Fornaro, Francesco Leone, Giovanni Brandi, Anna Saborowski, Astrid Lièvre, Richard A Hubner, Philip Johnson, Juan W Valle
This large multicentre database allowed for the development of a prognostic model that provides useful data on clinically-relevant unanswered questions. The cessation of chemotherapy after 8 cycles is recommended; CisGem is endorsed as the main backbone chemotherapy over GEMOX; CisGem should be preferred over single-agent gemcitabine in patients with PS2.
BACKGROUND & AIMS: Cisplatin-gemcitabine (CisGem) chemotherapy with immunotherapy is the standard of care first-line treatment for advanced biliary tract cancer (BTC). However, some relevant clinical questions cannot be answered through randomised clinical trials due to feasibility issues: the role of maintenance chemotherapy, the equivalence of the gemcitabine-oxaliplatin (GEMOX) regimen, the preferred treatment of patients with Performance Status (PS) 2. We thus built a large multicentre database, and created a prognostic model to provide corrected comparisons of outcomes of patients treated in the real-world setting.
METHODS: Retrospective analysis of patients treated at 15 European institutions with first-line chemotherapy for advanced BTC. We built a prognostic model of patients treated with CisGem, with internal validation, and used this model to provide corrected comparisons of different treatments.
RESULTS: 1947 patients were included, with 1022 treated with CisGem. Parameters included in the prognostic model were tumour differentiation, PS, extent of the disease (locally-advanced vs metastatic), albumin and CA19.9. Maintenance chemotherapy did not impact PFS or OS (n=79, median 17.0 with vs 23.7 months without, HR: 1.63 (95% Confidence Interval (CI) 0.95-1.74); p: 0.078). GEMOX was inferior to CisGem (n=1471, median 9.9 vs 11.4 months, Hazard Ratio for OS = 1.18, 95% CI: 1.00-1.41; p=0.049). CisGem was superior to gemcitabine in patients with PS 2 (n=233, median OS of 6.8 vs 3.6 months; HR:1.70 (95% CI: 1.30, 2.22); p:<0.001)).
CONCLUSION: This large multicentre database allowed for the development of a prognostic model that provides useful data on clinically-relevant unanswered questions. The cessation of chemotherapy after 8 cycles is recommended; CisGem is endorsed as the main backbone chemotherapy over GEMOX; CisGem should be preferred over single-agent gemcitabine in patients with PS2.
IMPACT AND IMPLICATIONS: This study tries to address some unresolved questioned in biliary tract cancer treatment. We confirmed that the Cisplatine-gemcitabine seems to be a better chemotherapy backbone as compared with GEMOX. We suggest that maintenance chemotherapy does not improve overall survival, and that cisplatine-gemcitabine should be preferred to single-agent gemcitabine in patient with a performance status of 2.