Formal discussant of this trial at the American Association for Cancer Research Annual Meeting, Rachna T. Shroff, MD, Associate Professor, Interim Chief of Hematology/Oncology, and Associate Director of Clinical Investigations, University of Arizona Cancer Center, said: “This is a very important trial. It is a whole new world in biliary tract cancers. For many years, we had only gemcitabine/cisplatin. The question was whether the addition of immunotherapy would help. Monotherapy with a checkpoint inhibitor had no dramatic efficacy.”

Rachna T. Shroff, MD

Dr. Shroff continued: “The majority of biliary tract tumors do not have a naturally immunogenic environment. Studies have shown that 11% of tumors did have T-cell infiltration, and that correlated with improved survival. This led to exploring whether chemotherapy and checkpoint inhibitors could be used together.”

She added: “This trial is important in the sense that it is slightly different from other trials. After eight cycles, cisplatin is stopped, and gemcitabine is used together with a checkpoint inhibitor vs gemcitabine alone. The continuation of gemcitabine could certainly impactresponse.”

Dr. Shroff concluded: “The TOPAZ-1 trial set the bar for gemcitabine/cisplatin plus durvalumab, which is the new gold standard. -KEYNOTE-966 establishes gemcitabine/cisplatin plus pembrolizumab as another first-line option for newly diagnosed biliary tract cancers. It is not clear yet if these two options are interchangeable. Further analysis of both trials is needed, but it is clear that chemotherapy plus immunotherapy is here to stay [for advanced biliary tract cancers]. Patient-reported outcomes and quality-of-life data will be meaningful and are forthcoming.” 

DISCLOSURE: Dr. Shroff has served as a consultant or advisor to Agios, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Debiopharm, Exelixis, Incyte, Merck, QED Therapeutics, Seattle Genetics, and Taiho Pharmaceutical and has received research funding from Agios, Exelixis, Halozyme, Merck, Pieris Pharmaceuticals, QED Therapeutics, Rafael Pharmaceuticals, and Taiho Pharmaceutical.