Robin Kate Kelley, MD, Professor of Clinical Medicine Hematology/IOncology, University of California, San Francisco, describes the need for better treatment plans for patients with biliary tract cancer.
Transcription:
Interestingly, the perihelia and distal cholangiocarcinoma, meaning the cancers that arise from the duct outside the liver or at the entrance to the liver, tend to be diagnosed at an earlier stage, with around half of them being diagnosed at stage 1 or 2. Because, as one might expect, when the duct gets a cancer, even a small one, it causes biliary obstruction, which leads to jaundice early on.
On the one hand, that’s good and that people might be diagnosed just with the cancer at a localized stage that’s amenable to surgery. There is a greater chance of being a candidate for resection or, in occasional cases, transplant for perihelia tumors with certain criteria in place, but they are still at high risk for recurrence. While again, it is good to have this biologic selection for an early signal of jaundice, getting an earlier diagnosis, there’s still a cancer that has a higher risk of recurrence.
Just to add another challenge, unique, I think, to biliary tract cancers is the biologic heterogeneity of these different anatomic sites which makes it very difficult to identify what treatments are working or which treatments aren’t. What I mean by that is that while biliary track cancers are rare, even within that relatively rare group, there are subsets defined by certain mutations in the intrahepatic location versus certain mutations or over-expression of proteins in the extrahepatic or gallbladder location that define very distinct genomic subgroups. It’s rare subgroups within a rare cancer. It makes it very difficult on a high level to identify what are those key, relevant, tractable subgroups that would respond to a particular treatment if we only drew our lens to them and knew what we were looking at. These rare subgroups are another challenge to making progress.
We do know that there is a small subgroup of between 1 and 3% of patients that have microsatellite instability across tumor types, whether it’s biliary tract cancer or colon cancer or breast cancer. There’s a subset of patients that have a phenomenon called microsatellite instability that leads to an accumulation of frameshift mutations throughout the tumor genome that lead to an exquisite sensitivity to immune checkpoint inhibitor therapy. Probably because of neoantigens, meaning new protein constructs being created by these mutations that make the tumor more recognizable to our immune system.
In that subset of patients with cholangiocarcinoma who have microsatellite instability, we know that immune checkpoint inhibitors have a very high response rate depending on which study subset one looks at, 30%, 40%, 50%. A subset of those are complete responses, and the median durations of response tend to be in the 24-month range or longer. Anecdotally, we all have some patients… I have multiple patients now who have been cured, as far as we can tell who have had complete responses and have not recurred. There is an exquisite sensitivity for that 1 to 3% group who have microsatellite instability.
Beyond that, though, it’s more of a shotgun effect. We aren’t sure who responds to immune checkpoint inhibitors. By themselves, immune checkpoint inhibitors as monotherapy have a pretty low response rate, around 5% in biliary tract cancer patients without microsatellite instability.
Who are those 5% of patients? We don’t know. There isn’t a dominant theme to identify them.
To learn more about Bilary Tract Cancer: https://checkrare.com/diseases/cancers/
