Daniel Brown, MD, FSIR, Highlights the Role of Liver-Directed Therapy in Cholangiocarcinoma

Daniel Brown, MD, FSIR, Vanderbilt University Medical Center, highlights the role of liver therapy in patients with cholangiocarcinoma.

Transcript
Hi there. My name's Daniel Brown. I'm the Director of Interventional Oncology and Vice Chair of Research at Vanderbilt University Medical Center in Nashville, Tennessee. I'm going to be debating that local, regional or liver-directed therapy is appropriate for patients with cholangiocarcinoma.

This patient group has a very difficult disease that in best-case scenario has survival that is still less than 13 months with the newest randomized trial, the TOPAZ data, which is the best that has ever been done with systemic chemotherapy. However, I believe that looking at that as definitive and a win for the patients, it's better than it's been, but we can still do better.

Surgery remains the standard of care for these patients as it is the only chance of cure, and that certainly is liver-directed as well. But the five-year overall survival (OS) with surgery is probably about 10% in the multicenter trial that was senior authored by Tim Pawlik.

Our goal with treatment is either to help get them to surgery or to help extend survival. We can do either of these things. There was a meta-analysis published in Onco Targets in 2019. There were 16 trials in that meta-analysis that had high level details of data, including OS, previous treatments, the dosimetry that was used for therapy, and the median OS with Y90, and that series of papers was 14.3 months. Importantly, the survival did not come with a great toxicity rate. The grade three or higher toxicity in that trial was under 8%.

Now, moving towards what could happen in the future, there was a recent phase two trial published in JAMA Oncology by the group in France led by Julien Edeline that had a combination of gemcitabine and cisplatin with Y90 that was given in the first cycle of therapy. In that trial, the median OS of the cohort treated with Y90 plus chemotherapy was 22 months and the median progression-free survival (PFS) was 14 months. So the median PFS when combining Y90 with systemic therapy is about the same or a little bit better than that of TOPAZ. These are not directly comparable trials, but it shows that there's a role. Additionally, nine of the patients in that trial were downstaged enough to go to surgery, and the median OS in that group surpassed the Pawlik trials group at two years, and had better numbers at two years than Pawlik's group did at one year for both PFS and OS.

I think there are a lot of potential roles for Y90 in these patients, and I think that in a comprehensive cancer environment, it should be considered in appropriate patients. Not patients with diffuse metastatic disease, not patients with poor performance status, but there certainly is a role for this treatment.