Real-World Efficacy and Safety of Durvalumab Plus Gemcitabine and Cisplatin for Advanced Biliary Tract Cancer

Confirming the Phase 3 TOPAZ-1 Trial

Andrea Casadei-Gardini, MD, San Raffaele Research Hospital, explains results from an early exploratory analysis of real-world data evaluating the efficacy of durvalumab plus gemcitabine and cisplatin among patients with advanced biliary tract cancer.

This real-world analysis confirmed the results seen in the TOPAZ-1 trial for progression-free survival, objective response rate, and safety. These data therefore support the use of the combination of durvalumab plus gemcitabine-cisplatin in clinical practice.

Transcript:

Hi. My name is Andrea Casadei-Gardini and I am an oncologist at San Raffaele Hospital in Milan. I am very happy to present our last paper about the efficacy of durvalumab in a real-world setting.

The TOPAZ-1 phase 3 trial reported a survival benefit with anti-PD-L1 durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancers.

Overall, about 700 patients with unresectable or metastatic cholangiocarcinoma were randomized to receive the anti-PD-L1 durvalumab or placebo in combination with cisplatin plus gemcitabine. The median overall survival for patients receiving the combination of chemotherapy plus durvalumab was 12.8 months, compared to 11.5 months for those receiving chemotherapy plus placebo, with a reduction in the risk of death of 20% in favor of [the] experimental arm.

Moving from a phase 3 trial to real world data, our study investigated the efficacy and the safety of this new standard treatment in daily clinical practice. The population included patients with unresectable, locally-advanced, or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centers. From February to November 2022, 145 patients were enrolled. In the final analysis, the median progression-free survival was 8.9 months, and the median overall survival was 12.9 months. The investigator-assessed confirmed overall response rate was 54.5%. Of them, complete response was about 5% of patient. Partial response was 29.6%. The disease control rate was about 87%.

Any grade adverse event occurred in about 95%. Grade 3/4 occurred in 35% of our patients. The most common adverse events were fatigue, neutropenia, anemia, and thrombocytopenia. All of these toxicities were correlated with the chemotherapy. The number of dead was 2.2%, and of these, none were related to immunotherapy. The rate of immune-mediated adverse events was 17%. Of them, grade 3/4 was 2.7%. No deaths or discontinuations were correlated with the immunotherapy. Neutrophil to lymphocyte ratio (NLR) and baseline alanine aminotransferase levels were associated with objective response to treatment. At univariate analysis, absence of viral infection, ECOG performance status >0 and NLR ≥3 were correlated with worse outcomes in term of progression-free survival.

In conclusion, our analysis reported the first real-world experience on the use of cisplatin and gemcitabine plus durvalumab in daily clinical practice. Our data mostly confirmed the result achieved in the TOPAZ-1trial, in terms of progression-free survival, overall survival, overall response rate, and safety, supporting the use of this combination in clinical practice.

Source:

Rimini M, Fornaro L, Lonadi S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data. Liver Int. Published online July 14, 2023. doi:10.1111/liv.15641